Annual Sickle Cell & Thalassaemia Conference (ASCAT) - October 2024

Topic: 001–Basic and translational

A. Ejaz¹, S. Liu¹, S. Holliman¹, C. Scott¹, D. Songdej², V. Viprakasit³, J. Davies¹, C. Babbs¹, D.R. Higgs¹

University of Oxford¹, Ramathibodi Hospital², Siriraj Hospital³

Zeta globin, an embryonic alpha-like globin, is repressed from 8 weeks gestation in humans.¹ Its de-repression is of clinical interest as transgenic mouse models have shown that it can substitute for alpha globin²—making it an attractive target for de-repressive gene editing strategies as a therapy for alpha thalassemia. Work from our lab examining cis regulatory factors has found that a discrete region of chromatin overlying zeta globin is deacetylated in mouse definitive erythropoiesis; while it is acetylated in primitive erythropoiesis when the gene is active.³ Previous work has also identified two trans regulatory factors—BCL11A and LRF. Knockout models of these factors show de-repression of zeta-globin to 15% of all alpha-like globin expression, less than that seen in primitive erythropoiesis when zeta globin is expressed maximally at 40% of all alpha-like globin.³ There are likely to be additional, as yet unidentified, factors involved in zeta globin regulation.

Human models of persistence of zeta globin expression are key to uncovering these factors. Studies in patients with compound heterozygous KLF1 mutations have found increased embryonic globin levels, likely due to KLF1's role in activating BCL11A and LRF (4). Some survivors of alpha thalassemia major (Barts hydrops fetalis syndrome) express high quantities of zeta globin, more than would be expected purely from deletions of the alpha globin genes. We have undertaken transcriptomic and chromatin analyses in these patients to characterize novel factors that may be involved in zeta globin regulation. We have identified several candidate genes, which have been intersected with results from CRISPR/Cas9 knockout screens of epigenetic modulators and transcription factors, to further refine our results. We are now undertaking exploratory studies of these factors to uncover the mechanisms by which they interact with the zeta globin locus, and plan ultimately to develop strategies for de-repressing zeta globin.

1. FB Piel, DJ Weatherall. The New England Journal of Medicine, 2014; 371(20), 1908–1916.

2. JE Russell, SA Liebhaber. Blood, 1998; 92(9), 3057–3063.

3. AJ King et al. Nature Communications, 2021; 12(1), 4439.

4. V Viprakasit et al. Blood. 2014; 123(10), 1586–1595.

Topic: 001–Basic and translational

M.J.M. Traets¹, J.F. Bos¹, S. Van der Veen², A. Kidane Gebremeskel³, B.A. van Oirschot¹, S.E.M. Schols⁴, M.N. Lauw⁵, E. Nur⁶, B.J. Biemond⁶, E.J. van Beers², M.H. Cnossen³, A. Rijneveld⁵, R. van Wijk¹, M.A.E. Rab¹

University Medical Center Utrecht, Central Diagnostic Laboratory¹, University Medical Center Utrecht, Center for Benign Hematology, Thrombosis and Hemostasis-Van Creveldkliniek², Erasmus MC Sophia Children's Hospital, Department of Pediatric Hematology and Oncology³, Radboud University Medical Center, Department of Hematology⁴, Erasmus University Medical Center Rotterdam, Department of Hematology⁵, Amsterdam University Medical Center, Department of Hematology⁶

Background: Hemoglobin SC (HbSC) is the second most common genotype variant of sickle cell disease (SCD). Patients with HbSC experience less hemolysis compared to patients with HbSS. This results in an elevated hematocrit with higher blood viscosity which is associated with an increased rate of retinopathy and acute chest syndrome. α-Thalassemia is a well-known genetic modifier of disease severity in SCD. However, whether co-inheritance of α- thalassemia correlates with blood viscosity and red blood cell (RBC) characteristics in HbSC disease is yet unclear.

Aims: Investigate whether co-inheritance of α-thalassemia correlates with viscosity, RBC hydration, deformability, sickling, and clinical complications in HbSC disease.

Methods: Patients with HbSC who visited outpatient clinics part of the SCORE consortium of The Netherlands were eligible to participate. Patients who received blood transfusion (<3 months), phlebotomy (<3 months) and/or hydroxyurea were excluded. Routine RBC laboratory parameters and percentage hypochromic (Sapphire Cell-Dyn) and dense RBCs (Advia Analyzer) were measured.

Blood viscosity was measured using a clone-plate viscometer (Brookfield). RBC hydration (Ohyper, OEImax), RBC deformability (EImax), and point of sickling (PoS) were assessed by osmotic and oxygen gradient ektacytometry using the Laser-Optical Rotational Red Cell Analyzer (Lorrca, RR Mechatronics). Oxygen affinity (p50) was measured with the Hemox-Analyzer (TCS). RBC adhesion to laminin (Biolamina) was measured using a microfluidic device (IBIDI).

Results: Thirty-six patients with HbSC (age range 6–58 years) were included of whom 15 patients (42%) had concomitant αthalassemia (-α/αα). Patients with concomitant α-thalassemia had a significantly higher RBC count, lower reticulocyte percentage, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) levels (Table 1). Further, a trend towards lower percentages of hypochromic cells and higher percentages of dense cells was observed. Blood viscosity was comparable between HbSC patients with and without α-thalassemia. Interestingly, we found a significant lower Ohyper (p = 0.009) and OEImax (Omax) (p = 0.004) in HbSC patients with concomitant α-thalassemia, indicating more RBC dehydration. RBC dehydration is generally believed to result in more dense cells with reduced deformability and increased tendency to sickle, leading to more vaso-occlusive episodes. Nonetheless, within our cohort, patients with HbSC and concomitant α-thalassemia exhibit increased RBC dehydration, yet without significant alterations in sickling tendency (PoS) or oxygen affinity (p50). Further, a significant lower occurrence of clinical complications was found in these patients.

Summary/Conclusion: Our findings demonstrate that co-inheritance of α-thalassemia modifies the RBC phenotype in HbSC disease. α-Thalassemia did not influence blood viscosity in these patients. Surprisingly, α-thalassemia was associated with more dehydrated RBCs. A less severe clinical phenotype was observed in HbSC disease in combination with α-thalassemia, possibly pointing towards beneficial effects of coinheritance of alpha thalassemia. Our findings might implicate that there is a difference between RBC dehydration and increased intracellular hemoglobin concentration, that is, dense cells. Nevertheless, our results are in contrast to previous findings reported in the scarce literature and warrant further investigation.

1. Nagel et al. Blood Reviews, 2003; 17(3), 167–178.

2. MH Steinberg et al. British Journal of Haematology, 1983; 55(3), 487–492.

3. JN Brewin et al. American Journal of Hematology 2022; 97(10), 1275–1285.

Topic: 001–Basic and translational

V. Bhat¹, G. Gibson¹, V.A. Sheehan²

Georgia Institute of Technology¹, Emory University School of Medicine²

Background: Sickle cell disease (SCD) is an inherited multisystem blood disorder that produces sickle-shaped erythrocytes that obstruct blood flow, leading to severe clinical complications, including painful vaso-occlusive events (VOE).¹ VOE are often initiated by adhesive interactions between sickle erythrocytes, leukocytes and endothelial cells. Hydroxyurea (HU), a disease-modifying therapy approved for pediatric and adult patients with SCD, increases fetal hemoglobin (HbF) levels, and has been demonstrated to reduce the frequency of pain crises. Much of the research into HU focuses on HbF induction; however, HU has many other effects, which can be investigated through transcriptomics.

Aims: To describe transcriptome changes in erythroid precursor cells (CD71+ is primarily a marker for cells of erythroid lineage but may also be expressed in proliferating neutrophils) with VOE, and correlate these with pathways affected by treatment with hydroxyurea.

Methods: Samples were obtained from patients receiving care at Texas Children's Hospital via informed consent on an IRB-approved protocol. CD71+ cells were collected from peripheral blood using magnetic bead extraction from 141 patients with SCD during steady state (and at the maximum tolerated dose of hydroxyurea) or during hospitalization for a VOE. RNA-Seq was performed with a 101 base pair, paired-end protocol on a NovaSeq. 6000 instrument. The R package SNM was used to adjust for the effect of multiple covariates, including age, sex, and batch effect. Differential gene expression analysis was performed using limma; genes with a Benjamini-Hochberg p < 0.05 were considered to be differentially expressed.² The R package fgsea was used for gene set enrichment analysis with the Molecular Signature Database as reference.

Whole-blood samples from 23 patients with SCD were collected before HU treatment (age <21 years) and at the maximum tolerated dose of hydroxyurea (HU MTD). RNA-Seq was carried out with a 150 base pair, paired-end protocol on a HiSeq. 4000 instrument. SNM was used to adjust for the effects of age, sex, and cell-type abundances on gene expression. Differential gene expression and biological pathway enrichment analyses of the pre-HU and HU-MTD samples were performed using limma and fgsea.

Table 1: Cohort summary. a = reported at sample level.

Results: We performed gene expression profiling of CD71+ cells to determine differentially expressed genes between steady state and VOE; 373 genes were upregulated, and 68 genes were downregulated at VOE. Pathways associated with cell proliferation, such as G2M checkpoint, E2F targets, and mitotic spindle were upregulated at VOE when compared to steady state. This is likely related to the increase in reticulocytes and neutrophils during a pain crisis as a consequence of stress erythropoiesis that is triggered by VOE-associated inflammation. Furthermore, the IL6 JAK STAT3 signaling and interferon alpha response pathways were elevated at VOE in comparison with steady state (Figure 1). While IL6 JAK STAT3 signaling is primarily linked to inflammation, the elevation of the interferon alpha response pathway may be a result of increased hemolysis that occurs in sickle cell disease patients during a VOE. In a previous study by Hermand et al, the interferon alpha response pathway was shown to be activated in the proteome of neutrophils in SCD at steady state when compared to healthy controls.³

A comparison of samples collected at pre-HU versus HU-MTD revealed that 1563 genes were upregulated, and 561 genes were downregulated after treatment. Genes known for their anti-inflammatory effects, such as TNFAIP3 and ADORA2A, exhibited increased expression after treatment. In addition, HU downregulated genes associated with heme metabolism and interferon alpha response pathways, implying that hydroxyurea modulates pathways that are elevated in CD71+ cells during pain crisis (Figure 2).

Conclusion: Samples collected during a VOE showed significant changes in the transcriptome of CD71+ cells when compared with samples collected at steady state. Multiple pathways linked to inflammation were elevated at VOE; these pathways are downregulated after treatment with HU, indicating that treatment with HU offers several benefits not directly linked to HbF induction that may prevent or reduce VOE severity.

1. Kato et al. Nature Reviews Disease Primers, 2018; 4, 10810.

2. Smyth GK. Statistical Applications in Genetics and Molecular Biology, 2004; 3, 3.

3. Hermand et al. Haematologica, 2020; 105, 2851–2854.

Topic: 001–Basic and translational

C.A. Hernandez Quiroga¹, M.J.M. Traets¹, W.W. van Solinge¹, A.W. Rijneveld², E.J.H. van Beers³, M.A.E. Rab², R. van Wijk¹

Department Central Diagnostic Laboratory-Research, University Medical Center Utrecht¹, Department of Hematology, Erasmus University Medical Center², Center for Benign Hematology, Thrombosis and Hemostasis-Van Creveldkliniek, University Medical Center Utrecht³

Background: Red blood cells (RBCs) are biconcave-shaped cells with viscoelastic membranes optimally adapted for oxygen delivery and gas exchange. RBCs have the antioxidant capacity to protect against reactive oxygen species (ROS). If this capacity is exceeded, damage can be inflicted, which disrupts the cellular deformability, structure, and membrane properties. Sickle cell disease (SCD) is a monogenetic disorder characterized by RBCs that deform from biconcave to typically sickle-shaped upon deoxygenation, leading to reduced deformability. SCD RBCs suffer from high levels of oxidative stress which may exhaust their physiological antioxidant capacity. Therefore, there is a need for a biomarker to evaluate differences in withstanding oxidative stress among patients and to monitor treatment response.

Aim: Evaluating RoxyScan key parameters as novel biomarkers that reflect the ability of SCD RBCs to withstand oxidative stress.

Methods: Patients with HbSS, HbSβ0, HbSβ+, or HbSC were eligible to participate. Patients who received blood transfusions <3 months prior to blood collection were excluded. RoxyScan was used to assess the susceptibility to oxidative stress. This novel application of the Lorrca (RR Mechatronics, Zwaag) measures deformability of RBCs in response to exposure to cumene hydroperoxide (CHP, 90 µM) during continuous shear (30 Pa). T-POD was defined as the time (seconds) required to reach a 10% decrease in deformability (expressed as EI, Elongation Index), calculated from a fitted curve. RoxyScan parameters were correlated to RBC sickling tendency (Point of Sickling, PoS, assessed by oxygen gradient ektacytometry), complete blood count (Cell Dyn Sapphire, Abbott), hemolysis markers and hemoglobin subfractions (HbF/HbS/HbSC) (HPLC, Tosoh G8). Additionally, ex vivo treatment with lglutamine (2 mM, 1 h) was performed and evaluated using RoxyScan.

Results: Fifty adult patients with SCD (HbSS/Sβ0, N = 26; HbSC, N = 20; HbSβ+ N = 4) and 21 healthy controls (HC) were included. HbSS/Sβ0 and HbSC RBCs showed a significantly lower T-POD than HC, indicating a faster deformability loss in response to the same level of oxidant exposure (HC 1739s (SD 238s), HbSS/Sβ0 776s (SD 328s), HbSC: 1031s (SD 225s), Figure 1A). HbSC RBCs showed a substantially more pronounced homogeneity in the response (Figure 1A). When correlating T-POD to hemolysis parameters in HbSS/Sβ0, a trend of inverse correlation with reticulocyte count (p = 0.09), lactate dehydrogenase (LDH, p = 0.10), and bilirubin (p = 0.068) was found (Figure 1B). Furthermore, T-POD was significantly correlated with PoS in HbSS/Sβ0 patients, showing a direct link between RBC sickling tendency and the ability to withstand oxidative stress. No significant T-POD correlations with sickling and hemolysis parameters were observed in HbSC patients. Ex-vivo treatment with l-glutamine showed a significant improvement in T-POD and EImin (Figure 1C), despite substantial variation in individual patient's response.

Conclusion: In this study, we demonstrated the applicability of RoxyScan as a novel method for assessing RBC susceptibility to oxidative stress in SCD. Patients with HbSS/Sβ0 and HbSC showed an earlier and more pronounced loss of deformability than HC. Furthermore, correlations between T-POD and laboratory parameters in HbSS/Sβ0 patients compared with HbSC patients demonstrated different characteristics in terms of oxidative stress. The results of l-glutamine experiments showed the benefit of the RoxyScan to evaluate treatment response and could help to identify patients benefiting from treatment with l-glutamine. Future studies are needed to explore the clinical applicability of the RoxyScan.

1. MAE Rab et al. Rapid and reproducible characterization of sickling during automated deoxygenation in sickle cell disease patients. American Journal of Hematology, 2019; 94(5), 575–584.

2. L Da Costa et al. Diagnostic tool for red blood cell membrane disorders: assessment of a new generation ektacytometer. Blood Cells, Molecules and Diseases, 2016; 56(1), 9–22.

3. SK Larkin et al. The RoxyScan is a novel measurement of red blood cell deformability under oxidative and shear stress. Scientific Reports, 2024; 14(1), 6344.

Topic: 001–Basic and translational

P. Shutt¹, R. Simpson¹, S. Babiker², E. Young³, M. Besser³, J. James¹

Sickle Cell Society¹, Guys and St Thomas NHS Foundation Trust and Evelina London Children's Hospital², Cambridge University Hospitals NHS Foundation Trust³

Background: Sickle cell disorder (SCD) is a chronic and progressive inherited blood disorder affecting millions worldwide. Recent data demonstrates a significant increase in mortality in young adults with SCD in the 15–25 age category, resulting in increased acute care utilisation rates with age, which significantly impacts quality of life, work and study activities, sleep, and social relationships.¹ Transition is a long process, which spans the period from early adolescence to adulthood and continues beyond transfer to adult care until the person is fully established as an adult patient in adult services. It represents a significant developmental phase.^2–3 Transitioning may disrupt the established relationship between the child, their parents, and their pediatric healthcare team. This can lead to gaps in care and a more challenging transition. Building relationships with the new adult care team is crucial. To enhance these relationships and ensure the best care, it is necessary to develop new tools that facilitate patient communication, especially since young patients may require hospital care throughout their lives.

Aims: The aim of this educational podcast is to offer a new approach to delivering education and information on the transition from pediatric to adult care. Led by the Patient Society (The Sickle Cell Society) and health care professionals, the initiative aims to improve communication between patients and parents during this critical stage.

Methods: The podcast was designed to generate discussion between health care professionals (Pediatric and adult consultants and a clinical psychologist) and patients. The panel exchange experiences and share insights from their clinics and lived experience, and offer tips for young patients and parents to communicate effectively with their doctors. It is promoted by The Sickle Cell Society via social media.

Results: The panel discussion related to continuity of care, access to adult care, emotional impact, education and empowerment, parental challenges, and the young brain. Possible solutions were discussed to make the transition process smoother and there were suggestions to establish routines and schedules that young patients could rely upon to get the most out of their care.

Summary/Conclusion: Transition from pediatric to adult sickle cell care can be difficult for both parents and children. Consistent communication, along with a planned approach to support from health care professionals and parents, are fundamental to making a significant impact over the transition period. It is crucial to involve the young patient in any decision-making, and gradually introduce changes, slowly empowering them to take over responsibility for their own care. Healthcare Trusts and clinicians need to enable this process to reduce the anxiety and stress experienced by patients and families during this critical time.

1. A Boucher et al., Rethinking care models for young adult with sickle cell disease. Jama Health Forum, 2023; 4(5), e230877.

2. A Renedo et al., Not being heard–barriers to high quality unplanned hospital care during young people's transition to adult services–evidence from “this sickle cell life” research. BMC Health Services Research, 2019; 19, 876.

3. A Farre, JE McDonagh. Helping healthy services to meet the needs of young people with chronic conditions: towards a developmental model for Transition. Healthcare (Basel), 2017; 5(4), 77.

Topic: 001–Basic and translational

S.N. Siana Nkya¹, C.N. Collin Nzunda¹, E.J. Emmanuel Saukiwa¹, F.K. Frida Kaywanga¹, E.B. Eliud Buchard¹, H.C. Heaven Christopher¹, C.D. Collet Dandara², E.N. Enrico Novelli³, E.C. Emile Chimusa⁴, J.M. Julie Makani¹

Muhimbili University of Health and Allied Science¹, University of Cape Town², South African Medical Research Council³, Northumbria University⁴

Background: Hydroxyurea (HU) is the only FDA-approved drug for sickle cell disease (SCD) since 1998, known for increasing fetal hemoglobin (HbF) levels, a key modifier of SCD. It reduces vaso-occlusive crises (VOC) and the need for transfusions in responsive patients. Response to HU varies, with treatment typically requiring 6–12 months to determine effectiveness based on hematological changes. In many African countries, fixed doses are common due to limited access and monitoring capabilities. Genetic markers can predict HU response before treatment, unlike molecular and hematological profiles which are post-treatment. Most pharmacogenomics studies have been conducted outside Africa, with no genetic tests yet developed for HU response prediction. This study identified genetic variants in CYP2C9, KLF10, BCL11A, ARG2, HBG1, SAR1A, MYB, and NOS1 as potential predictors of HU response.

Aim: To investigate the genetic determinants of HU treatment response and their association with various genetic variants in CYP2C9, KLF10, BCL11A, ARG2, HBG1, SAR1A, MYB, and NOS1.

Methodology: This study involved 150 SCD patients from Muhimbili National Hospital, Amana, and Temeke hospitals, aged 5 years and above, meeting specific hematological criteria for hydroxyurea (HU) treatment, followed for 6 months. Exclusions included pregnancy, lactation, and chronic transfusion therapy. Patients received 20 mg/kg daily HU, with monthly follow-ups assessing HbF levels, total hemoglobin, MCV, and MCH. DNA was extracted from blood samples, quantified, and sequenced using a custom Ampliseq panel on a MiSeq sequencer. Quality control, variant calling, and annotation were performed using FastQC, GATK, BCFTOOLS, and ANNOVAR. Linear mixed models analyzed the impact of HU on hematological indices. SNPs were analyzed for pathogenicity and distribution across African descent populations, with PCA and MAF analyses elucidating genetic structure and diversity. Pathway enrichment analysis using GeneMania and Enrichr provided insights into the functional implications of HU-associated variants.

Results: This longitudinal study monitored 148 individuals with sickle cell disease (SCD) in Tanzania over six months, with monthly visits. HU treatment resulted in slight increases in RBC, HB, and MCV levels, while reticulocytes decreased. No significant changes were found in platelets, WBC, and HbF levels. Patients were classified as responders or non-responders based on HbF levels, with significant differences in hematological indices observed between the groups. Responders exhibited the highest mean increases in HbF and MCV, whereas poor responders had higher WBC and reticulocytes. Genetic analysis of 49 individuals identified 152,327 variants, with significant differences in non-synonymous, function-altering variants between responders and non-responders. Key pathogenic SNPs were identified in genes like HAO2, BCL11A, WAC, CYP2C9, CYP2E1, MYB, HBG1, NOS1, and ARG2, with different distribution patterns in good and poor responders. Principal Component Analysis (PCA) revealed distinct genetic variation patterns linked to HU response, with poor responders showing higher variation in rare variants and pathogenic SNPs. Pathway enrichment analysis highlighted associations with drug metabolism, arginine and proline metabolism, and the metabolism of xenobiotics by cytochrome P450, suggesting these genes may influence HU treatment response.

Conclusion: Our study investigated the genetic factors influencing the response to HU treatment in SCD in Tanzania. We analyzed genetic variants at 12 loci and identified distinct profiles associated with responders and nonresponders. Key findings include the influence of specific loci on HbF levels and HU metabolism, and the presence of pathogenic and rare genetic variants in non-responders. These insights suggest the genetic complexity of HU response and underscore the potential for developing a pharmacogenomics panel to guide treatment decisions. Our research enhances the understanding of genetic interactions in HU treatment, paving the way for personalized medicine and improved outcomes for individuals with SCD.

1. How I use hydroxyurea to treat young patients with sickle cell anemia. Blood American Society of Hematology [Internet]. https://ashpublications.org/blood/article/115/26/5300/130 853/How-I-use-hydroxyurea-to-treat-young-patients-with

2. L. Tshilolo et al. Hydroxyurea for children with sickle cell anemia in Sub-Saharan Africa. The New England Journal of Medicine, 2019 [cited 2023 Dec 12]; 380, 121–131. https://pubmed.ncbi.nlm.nih.gov/30 501 550/

3. CC John et al. Hydroxyurea dose escalation for sickle cell anemia in Sub-Saharan Africa. The New England Journal of Medicine [Internet], 2020 [cited 2023 Dec 12]; 382, 2524–2533. https://pubmed.ncbi.nlm.nih.gov/32 579 813/

4. PT McGann et al. Robust clinical and laboratory response to hydroxyurea using pharmacokinetically guided dosing for young children with sickle cell anemia. The American Journal of Hematology [Internet], 2019 [cited 2023 Dec 12]; 94, 871–879. https://onlinelibrary.wiley.com/doi/full/10.1002/ajh.25510

5. CC John et al. Hydroxyurea dose escalation for sickle cell anemia in Sub-Saharan Africa. The New England Journal of Medicine [Internet], 2020 [cited 2024 Jan 10]; 382, 2524–2533. https://europepmc.org/article/med/32 579 813

6. CC John et al. Hydroxyurea dose escalation for sickle cell anemia in Sub-Saharan Africa. The New England Journal of Medicine [Internet], 2020 [cited 2023 Dec 12]; 382, 2524–2533. https://europepmc.org/article/med/32 579 813

7. C Ginete et al. Are genetic modifiers the answer to different responses to hydroxyurea treatment?—A pharmacogenetic study in sickle cell anemia Angolan children. International Journal of Molecular Sciences [Internet], 2023; [cited 2023 Dec 12], 24. https://pubmed.ncbi.nlm.nih.gov/37240136/

8. AL Walker et al. Transcellular movement of hydroxyurea is mediated by specific solute carriertransporters. Experimental Hematology [Internet], 2011 [cited 2023 Dec 12]; 39, 446–4456. https://pubmed.ncbi.nlm.nih.gov/21256917/

9. NS Green, S Barral. Emerging science of hydroxyurea therapy for pediatric sickle cell disease. Pediatric Research [Internet], 2014 [cited 2023 Dec 12]; 75, 196–204. https://pubmed.ncbi.nlm.nih.gov/24252885/

10. SM Rappaport. Genetic factors are not the major causes of chronic diseases. PLoS One [Internet], 2016 [cited 2023 Dec 12], 11. https://pubmed.ncbi.nlm.nih.gov/27105432/

11. VA Sheehan et al. Whole exome sequencing identifies novel genes for fetal hemoglobin response to hydroxyurea in children with sickle cell anemia. PLoS One [Internet], 2014 [cited 2023 Dec 12], 9. https://pubmed.ncbi.nlm.nih.gov/25360671/

Topic: 002–Novel therapies, gene therapies, bone marrow transplant and emerging diagnostics

A.P. Patwardhan¹, A.P.P. Patel¹, S.O. Oshabaheebwa², C.A.D. Delianides², M.A.S. Suster², P.M. Mohseni², U.A.G. Gurkan², V.A.S. Sheehan¹

Emory University School of Medicine¹, Case Western Reserve University²

Background: Sickle cell disease (SCD) is a severe inherited blood disorder in which abnormal hemoglobin stacks and polymerizes, particularly under hypoxia, resulting in rigid red cells. The resulting red cell is rigid and poorly deformable; this contributes greatly to SCD clinical complications of pain and organ damage. Several SCD therapies aim to improve deformability, but we lack reliable, consistent across devices methods of measuring deformability under normoxia and hypoxia. In response to this need, we developed and analytically and clinically validated the novel Microfluidic Impedance Red Cell Assay (MIRCA) for use in SCD patient care.

Aims: We propose to assess the ability of MIRCA readouts to identify individuals at risk for complications despite hydroxyurea therapy, to guide initiation of second-line therapies proactively, before the individual suffers VOE or acute chest syndrome (ACS). Additionally, we propose to assess the impact of chronic transfusion therapy on red cell deformability, to determine if there is a role for adjunct drug therapy to normalize the remaining recipient cells.

Methods: MIRCA devices were fabricated using photolithography and polydimethylsiloxane (PDMS) micro-molding protocols. The microfluidic devices comprised six microcapillary arrays of widths 12, 10, 8, 6, 4, and 3 μm, with each array coupled with a pair of gold electrodes. Venous blood samples were collected in EDTA tubes under an IRB-approved protocol. To induce hypoxia, washed RBCs were suspended at 20% hematocrit in a 1.5% (w/v) sodium metabisulphite in 1× PBS buffer and incubated for 3 min at room temperature. For normoxia, RBCs from the same donors were suspended at 20% hematocrit in PBS and incubated with the same conditions. Samples were then perfused through the microfluidic device at a constant inlet pressure. After 10 min of perfusion, the change in electrical impedance across each array was used to calculate an occlusion index (OI), Hypoxia occlusion index (HOI), and normoxia occlusion index (NOI) was calculated for each sample. Complete blood count, absolute reticulocyte count and percent dense red blood cells (%DRBC) were obtained using an ADVIA hematology analyzer. Hemoglobin profiles were obtained via chart review, from clinical hemoglobin electrophoresis.

Results: Univariate correlation analysis using spearman's rho (rs) showed significant (p < 0.05) associations of OI with absolute reticulocyte count (rs = 0.42), RBC distribution width (rs = 0.76), hemoglobin (rs = −0.58), and percent fetal hemoglobin (rs = 0.72). In multiple linear regression, HbSS/SB0 genotypes (p < 0.01), adults (p = 0.01), and dense RBCs (cells with a density >1.11 mg/mL, p < 0.01) were associated with OI. Analysis of HOI and NOI of cross-sectional individuals by %HbS is shown in Figure 1. Patients with ≥1 vasoocclusive events (VOE+) or that received medical acute care in the past year had higher median NOIs than those without (p = 0.03).

Conclusions: We have established correlations between MIRCA readouts and the number of acute events requiring hospitalization in the prior year. We have demonstrated that the MIRCA captures a subpopulation of recipient cells unmodified by rigorous suppression of HbS through chronic transfusion therapy. We therefore conclude that MIRCA can be used to augment clinical decision-making in the care of individuals with SCD. We propose to use MIRCA to identify and monitor individuals with SCD in need of second line therapies by monitoring changes in their red cell deformability and to assess safety and efficacy of chronic transfusion therapy with and without the addition of a second line disease-modifying therapy, voxelotor. We envision the MIRCA in every sickle cell center, providing inexpensive, easy to use red cell function testing to complement and extend conventional laboratory testing in SCD patient care.

1. Y Man et al. Lab Chip, 2021, 21 (6), 1036–1048.

Topic: 002–Novel therapies, gene therapies, bone marrow transplant and emerging diagnostics

S. Chatzidavid¹, P. Flevari¹, V. Bartzi¹, A. Kopsaftopoulou¹, S. Syriopoulou¹, G. Anastasiadis¹, M. Dimopoulou¹

Thalassemia and Sickle Cell Disease Unit, Laikon General Hospital, Center of Expertise in Rare Hematological Diseases¹

Introduction: Many non-transfusion dependent (NTD) β-thalassemic patients (pts) with mild genotypes become TD (neo-TDT) late in adulthood. Entering a program of regular transfusions seriously affects quality of life. The frequency of alloimmunization is higher in adults. Especially in cases with multiple alloantibodies or history of delayed hemolytic transfusion reactions (DHTRs) it is almost impossible to transfuse regularly even if there are strong indications such as cardiac comorbidities. Treatments for correcting anemia without transfusion in alloimunized patients are very limited.

Aim: The aim of this study is to examine the impact of Luspatercept in thalassemic pts who become TD late in life, or pts with alloantibodies and DHTRs for whom it is impossible to sustain a regular transfusion program.

Methods: Clinical and laboratory characteristics were collected retrospectively from pts' medical files. Luspatercept was administered SC at a dose of 1.0 mg/kg every 21–28 days. Special approval for off-label use in one NTD pt was obtained according to local legislations.

Results: Eight pts with thalassemia intermedia treated with luspatercept are reported. Their genotype and clinical characteristics are shown in Table 1. Seven of them had become TD at a median age of 71 years (range 48–80) One patient pt with a δβ/β0 genotype had a history of multiple DHTRs with hyperhemolysis and had previously received treatment with steroids and intravenous immunoglobulins. She had several comorbidities and multiple indications to initiate a regular transfusion program but remained NTD with very low hemoglobin (Hb) levels as it was impossible to transfuse her with compatible blood. Another patient with IVSI-6/IVSI-6 genotype was also alloimunized and had a history of DHTRs and even though she started a regular transfusion program finding compatible blood to transfuse was challenging. Mean hemoglobin levels pre and post Luspatercept treatment are shown in Figure 1. All pts have higher mean Hb values post treatment, even if they have achieved TI.

Conclusions: NTD pts who become neo-TD late in life due to complications can achieve TI when treated with Luspatercept. Cardiac morbidities were usually exclusion criteria in clinical trials but even elderly frail pts can tolerate treatment well and benefit with sustained anemia amelioration. Especially for pts with alloimmunization and/or history of DHTRs including hyperhemolysis, in whom finding compatible blood and maintaining a regular transfusion program is very challenging, anemia can be improved without transfusions with luspatercept treatment.

Table 1. Genotypic and Clinical Characteristics.

1. KM Musallam et al. Revisiting the non-transfusion-dependent (NTDT) vs. transfusion-dependent (TDT) thalassemia classification 10 years later. The American Journal of Hematology, 2021; 96(2), E54–E56.

2. MD Cappellini et al. BELIEVE Investigators. A phase 3 trial of luspatercept in patients with transfusion-dependent β-thalassemia. The New England Journal of Medicine, 2020; 382(13), 1219–1231.

Topic: 002–Novel therapies, gene therapies, bone marrow transplant and emerging diagnostics

J. Okalova¹, J.S. Alexander¹, C. Chambliss¹, Z. Zhu², Y. Xie², M. Addington-Hall², O. Slessareva², T. Luo², B. Ferencz², I. Oparaocha², N. Uchida³, J.F. Tisdale³, H.T. Spencer¹, D. Archer¹, R.J. Orentas²

Emory University¹, Caring Cross², NHLBI, NIH³

Background: Sickle cell disease (SCD) is a monogenic hemoglobin (Hgb) disorder characterized by a single point mutation in the β-globin gene which causes Hgb polymerization under low oxygen tension and sickling of red blood cells (RBCs) which in turn drives severe systemic injury. Gene addition technologies like hematopoietic stem cell (HSC) targeted lentiviral (LV) gene therapy are among the most promising curative strategies for SCD. Although both LV and Crispr-based approaches have recently been approved for marketing by the US FDA, their pricing in the millions of dollars is significant barrier to widespread adoption.¹

Aims: To improve upon current gene-therapy approaches for sickle cell disease we sought to improve vector characteristics and to create low-cost workflows that will allow for wider availability of this potentially curative approach. Here we seek to improve LV titer, transduction efficiency, along with suppression of native sickle-globin, and to thereby generate successful therapeutic outcomes that will be used in point-of-care therapeutic centers.

Methods: One such improvement targets LV orientation: the relationship between the DNA encoding the β-globin gene in the LV and the promoter driving healthy β-globin gene expression. We created a forward-oriented β-globin-expression vector with an improved titer that results in more efficient transduction of human CD34+ cells in vitro, in human reconstituting CD34+ cells in xenografted mice, and in rhesus reconstituting CD34+ cells.² This construct was further modified to include one or two shRNAs that would suppress native globin expression in the transduced cell population. We report here on further optimization of LVs that in addition to forward orientation, also express shRNA that decreases native β-globin and sickle-globin, which could enhance the assembly of corrected Hgb tetramers.

Results: Seven unique constructs which varied in anti-β-globin shRNA sequences, packaging elements, and regulatory elements, were transduced into MEL-BB88 cells and expanded for 2 weeks. Genomic DNA (gDNA) was collected for vector copy number (VCN) analysis, and treated with 10 µM hemin to induce Hgb expression. Five days after hemin-induction, cells were harvested for benzidine staining and immunoblot analysis to validate globin expression. Sca-1+ HSC/progenitor (HSPC) BM cells were isolated from Towne's humanized SCD donor mice prior to stimulation for 48 h with cytokines, then transduced at an MOI of 24 twice, 24 h apart. To assess the in vivo engraftment potential of the transduced HSPCs, 2.5 × 10⁶ cells were transplanted into lethally irradiated CD45.1 recipient mice. Peripheral blood (PB) was sampled at 2-week intervals for PBMC chimerism and lineage engraftment, Hgb electrophoresis, Lorrca OxygenScan and OsmoScan assays, and PB VCN. Whole BM from engrafted recipients was collected at 30 weeks and used for secondary transplantation assays which were again analyzed over 24 weeks for PB engraftment, VCN, and donor Hgb expression.

LVs were produced at varying titers and all successfully transduced MEL-BB88 cells with VCNs between 1 and 5 that were maintained following hemin induction. Interestingly, variations in RRE elements dramatically affected human globin expression in vitro. Furthermore, the transplanted mice engrafted fully with HSPCs transduced with multiple vectors. Notably, mice transplanted with HSPCs transduced with vector CX0066p (LCR-Enhancer-P-HBB-shmiR-3g1.223 + 3g2.30a-R1) maintained a VCN of 0.2–0.4 in PB for the 30-week duration of the primary transplant. Cellulose acetate gels of RBCs from PB showed ~40% HbA in a background of HbS. The P50 right-shifted towards normal, RBC counts increased, WBC counts decreased, and OxygenScan parameters were all corrected towards controls and away from those values obtained from mice transplanted with mock transduced HSPCs. EI max and EI min increased while pO₂@95% decreased. Lastly, the RBC sickling was corrected in an in vitro sickling assay.

Conclusion: based on LV titer, MEL cell expression, transduction efficiency, engraftment of modified cells, in vivo globin expression, anti-sickling activity, and oxygen transport, these constructs provide outstanding Hgb expression and phenotype correction.

Consequently, these candidates serve as a solid foundation for future human gene therapy products in the treatment of SCD.

1. G Morgan et al. Scientific Reports, 2024, 14, 2739.

2. N Uchida et al. Nature Communications, 2019, 10, 4479.

Topic: 002–Novel therapies, gene therapies, bone marrow transplant and emerging diagnostics

C.P.M. Minniti¹, K.R. Rivlin², J.A. Ahn³, W.A.E. Engelman³, B.A.S. Stuart³

Albert Einstein College of Medicine¹, Jacobi Medical Center², Fulcrum Therapeutics³

Background: Pociredir, a potent and selective orally-administered small-molecule inhibitor of Embryonic Ectoderm Development, demonstrated robust induction of fetal hemoglobin (HbF) expression up to ~40% of total hemoglobin (Hb) in primary human cell and murine models of sickle cell disease (SCD). HbF (α2γ2) prevents the pathologic polymerization of HbS in the low oxygen milieu of the microcirculation. People with SCD who also possess hereditary persistence of HbF (HPFH) have attenuated pathology when HbF levels are > approximately 25%. Therefore, increasing HbF can potentially prevent or reduce disease-related pathophysiology, including hemolysis, vaso-occlusive crises (VOCs), end organ damage, and mortality. Multiple ascending doses from a Phase 1 study of pociredir in healthy volunteers demonstrated robust target engagement, with potent induction of HBG (Hb subunit γ) mRNA. It was generally well tolerated, with no serious drug related safety issues.

Aims: Assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of pociredir in adults living with SCD.

Methods: The Phase 1b open-label study investigating pociredir is a multi-dose, sequential cohort trial conducted in adults with SCD. Cohorts 1–3 included ± HU; subsequent cohorts will be pociredir monotherapy only. The first cohort enrolled ten adults who received pociredir, 6 mg once daily (oral) for 4 weeks, with the option to continue dosing for an additional 8 weeks at the same dose. Two adults enrolled in a 2-mg cohort for 12 weeks; a third cohort of 12 mg enrolled four adults. The 12 mg cohort is now enrolling for a 12 week dosing period. Additional cohorts may be added based on available safety and PK data from existing participants. Primary endpoints are safety, tolerability, and PK profile. Secondary and exploratory endpoints include HbF induction in peripheral blood and other SCD biomarkers and clinical endpoints. We report the results from the first three dose cohorts of 6 (n = 10), 2 (n = 2) and 12 mg (n = 4).

Results: Average age of combined cohorts (N = 16) is 30.25 years (range: 21–48), with 31.25% (n = 5) male. The mean HbF baseline is 9.26% (range: 3.2%–19.9%). Five were on HU, and all have the HbSS genotype. As of 29 September 2023 there were 23 TEAEs in 10/16 adults (63%) with 8/23 possibly related to study drug (headache [x²], lip numbness, diarrhea, tinnitus, fatigue, drowsiness, nausea); they were all mild in severity, non-serious, and resolved quickly; all patients remained on study drug. 4 (of 23) TEAEs were VOCs; one was reported as an SAE with acute chest syndrome and was deemed unrelated to study drug, and occurred in a patient who was non-adherent to pociredir. The other three VOCs were non-serious, mild or moderate in severity, and were treated in an outpatient setting. There were no lab-related AEs, deaths, or discontinuations due to TEAEs.

All participants adherent to therapy (based on PK measurements) had HbF induction, with absolute HbF increases up to 9.8% and 10.0% over baseline in the 6 and 12 mg cohorts respectively. Pociredir demonstrated dose dependent increases in HbF which were not affected by HU use. There was improvement in biomarkers of hemolysis (total bilirubin, absolute reticulocyte count, total hemoglobin) in the majority of patients.

Summary/Conclusion: Pociredir was generally well tolerated with eight mild and non-serious drug-related TEAEs and no TEAEs resulted in drug discontinuations. All adherent participants in the 2, 6, and 12 mg cohorts showed consistent increases in HbF. The study is currently enrolling in the 12 mg dose cohort. (ClinicalTrials.gov ID: NCT05169580) Updated study results to be presented.

Topic: 002–Novel therapies, gene therapies, bone marrow transplant and emerging diagnostics

J. de la Fuente¹, F. Locatelli², P. Lang³, R. Meisel⁴, S. Corbacioglu⁵, D. Wall⁶, A.M. Li⁷, A.J. Shah⁸, B. Carpenter⁹, J.L. Kwiatkowski¹⁰, M. Mapara¹¹, R.I. Liem¹², R. Handgreitinger¹³, M.D. Cappellini¹⁴, A. Kattamis¹⁵, S. Sheth¹⁶, M. Algeri², S. Grupp¹⁰, P. Kohli¹⁷, L. Ross¹⁷, Y. Bobruff¹⁷, C. Simard¹⁷, T. Liu¹⁷, P.K. Morrow¹⁸, W. Hobbs¹⁷, H. Frangoul¹⁹

Imperial College Healthcare NHS Trust, St Mary's Hospital¹, IRCCS, Ospedale Pediatrico Bambino Gesù Rome, Catholic University of the Sacred Heart², University of Tübingen³, Division of Pediatric Stem Cell Therapy, Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty,⁴, University of Regensburg⁵, The Hospital for Sick Children/University of Toronto⁶, 6BC Children's Hospital, University of British Columbia⁷, Stanford University⁸, University College London Hospitals NHS Foundation Trust⁹, Children's Hospital of Philadelphia and Perlman School of Medicine, University of Pennsylvania¹⁰, Division of Hematology and Oncology, Columbia University¹¹, Ann & Robert H. Lurie Children's Hospital of Chicago¹², Children's Hospital University¹³, University of Milan¹⁴, National and Kapodistrian University of Athens¹⁵, Joan and Sanford I Weill Medical College of Cornell University¹⁶, Vertex Pharmaceuticals Incorporated¹⁷, CRISPR Therapeutics¹⁸, Sarah Cannon Research Institute at The Children's Hospital at TriStar Centennial¹⁹

Background: Exagamglogene autotemcel (exa-cel) is a non-viral cell therapy that reactivates fetal hemoglobin (HbF) via ex vivo CRISPR-Cas9 gene-editing of autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) at the erythroid-specific enhancer region of BCL11A. Exa-cel is approved as a one-time treatment for patients (pts) with transfusion-dependent β-thalassemia (TDT) based on positive results from a pre-specified interim analysis of the CLIMB THAL-111 phase 3 trial.

Aims: To evaluate longer-term efficacy and safety of exa-cel in pts with TDT.

Methods: CLIMB THAL-111 is a 24-month (mo), phase 3 trial of exa-cel in pts age 12–35 y with TDT and a history of ≥100 mL/kg/y or ≥10 U/y packed red blood cell (RBC) transfusions in the 2 y before screening. Enrollment and dosing are complete; trial is ongoing. Primary endpoint is transfusion independence defined as proportion of pts maintaining a weighted average hemoglobin (Hb) ≥9 g/dL without RBC transfusion for ≥12 consecutive mos (TI12). Key secondary endpoint is proportion of pts maintaining a weighted average Hb ≥9 g/dL without RBC transfusion for ≥6 consecutive mos (TI6). Evaluable pts must have ≥16 mos of follow-up after exa-cel infusion. Evaluation of TI12 and TI6 started 60 days after last RBC transfusion for post-transplant support or TDT management. Pts completing trial enrolled in long-term follow-up Study 131. Mean (SD) values shown except where noted.

Results: As of 19 March 2024, 56 pts (mean age 21.2 [range 12–35] y; 20 [35.7%] age ≥12 to <18 y; 35 [62.5%] with severe genotypes [β0/β0 or β0/β0-like], median annualized transfusion volume 206.7 mL/kg) received exa-cel; median follow-up 33.3 (range 3.1–62.3) mos. Of these, 43 pts completed 2 y of follow-up in CLIMB-THAL-111 and enrolled in Study 131. Following infusion, all pts engrafted neutrophils and platelets (median 29 and 43.5 days, respectively). Of the 52 pts evaluable for primary and key secondary endpoints, 49 (94.2%) achieved TI12 and TI6 (95% CI: 84.1%, 98.9%). Pts achieving TI12 stopped transfusions 32.7 (SD, 17.3) days after exa-cel infusion and remained transfusion independent for 31.0 (range, 12.8, 59.4) mos. For the 3 pts not achieving TI12, two stopped transfusions and achieved TI12 in Study 131 and one had been transfusion free for 10.6 months before a transient episode of anemia related to viral gastroenteritis (since then has been transfusion free for 3.4 months). For all pts, mean total Hb was 11.6 g/dL at Month 3 (≥12 g/dL Month 6 onward) and HbF was 8.0 g/dL at Month 3 (≥11 g/dL Month 6 onward) with pancellular distribution (≥95% RBCs expressing HbF Month 6 onward). Proportion of edited BCL11A alleles was stable over time in bone marrow CD34+ and peripheral blood nucleated cells. Pts not yet evaluable and with sufficient follow-up were also transfusion-free. Quality-of-life (QOL) measures showed clinically significant improvements.

All pts had ≥1 adverse event (AE), most were Grade 1 or 2; 50 (89.3%) pts had AEs of Grade 3 or 4 severity. Most common AEs were febrile neutropenia (60.7%), headache (55.4%), and stomatitis (53.6%). Most AEs and serious AEs (SAEs) occurred within first 6 mos after infusion. As previously reported, 2 pts (3.7%) had SAEs considered related to exa-cel which all resolved. There were no deaths, discontinuations, or malignancies.

Conclusions: Exa-cel treatment resulted in early and sustained increases in Hb and HbF, leading to transfusion independence in >90% of pts with TDT and improved QOL which was maintained over the longer term for up to >5 years. Safety profile of exa-cel remains generally consistent with myeloablative busulfan conditioning and autologous transplantation. These results confirm the potential for exa-cel to provide a one-time functional cure to pts with TDT.

1. Locatelli et al. The New England Journal of Medicine, 2024; 390, 1663–1676.

Topic: 002–Novel therapies, gene therapies, bone marrow transplant and emerging diagnostics

J. de la Fuente¹, F. Locatelli², A.M. Li³, A. Sharma⁴, M. Mapara⁵, P. Lang⁶, S. Corbacioglu⁷, D. Wall⁸, M.J. Eckrich⁹, P. Kohli¹⁰, S. Zhang¹⁰, S. Imren¹⁰, N. Li¹⁰, T. Liu¹⁰, J. Rubin¹⁰, G. Xu¹⁰, W. Hobbs¹⁰, S. Grupp¹¹, H. Frangoul¹²

Imperial College Healthcare NHS Trust, St Mary's Hospital¹, IRCCS, Ospedale Pediatrico Bambino Gesù Rome, Catholic University of the Sacred Heart², BC Children's Hospital, University of British Columbia,³ Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital⁴, Department of Medicine, Division of Hematology/Oncology, Columbia University⁵, University of Tübingen⁶, University of Regensburg⁷, The Hospital for Sick Children/University of Toronto⁸, Sarah Cannon Pediatric Transplant and Cellular Therapy Program at Methodist Children's Hospital⁹, Vertex Pharmaceuticals Incorporated¹⁰, Division of Oncology, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania¹¹, Sarah Cannon Research Institute at The Children's Hospital at TriStar Centennial¹²

Background: Exagamglogene autotemcel (exa-cel) is a CRISPR/Cas9 gene-edited cell therapy shown to eliminate red blood cell (RBC) transfusions in patients (pts) with transfusion-dependent β-thalassemia (TDT) and VOCs in pts with severe sickle cell disease (SCD).

Methods: CLIMB THAL-111 and CLIMB SCD-121 are 24-mo, phase 3 trials of exa-cel in pts age 12–35 years (y) with TDT and SCD, respectively. Changes in patient-reported outcomes measures EQ-5D-5L (including descriptive system and visual analog scale [VAS]), Functional Assessment of Cancer Therapy Bone Marrow Transplant (FACT-BMT including FACT-General [FACT-G] and bone marrow transplant subscale [BMTS]), Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me; SCD), and 11-point pain Numerical Rating Scale (NRS; SCD) for adults and EQ-5D-Y, NRS, and Pediatric QoL Inventory (PedsQL) for adolescents were assessed as secondary endpoints.

Results: As of 19 March 2024, 34 adults (≥18–≤35 y) and 18 adolescents (≥12–<18 y) with TDT followed for ≥16 months were evaluated. At baseline, mean EQ-5D-5L health utility US index score (0.88 [SD,0.16]; n = 34) was near general population norm and in line with adults with TDT. Through month 36, improvements were seen in EQ-5D-5L health utility US index and EQ VAS (mean [SD] change 0.04 [0.18] and 10.5 [20.8]; MCID 0.078 and 7–10, respectively; n = 16), FACT-G Total (7.3 [16.9]; MCID 3 to 7; n = 16) and BMTS (4.5 [5.2]; MCID 2 to 3; n = 16). For adolescents, EQ VAS improved through month 24 (7.3 [16.4]; n = 14); PedsQL total score improved through month 24 (12.2 [11.8]; MCID 4.36; n = 13).

As of 19 March 2024, 28 adults and 11 adolescents with SCD followed for ≥16 months were evaluated. At baseline, mean EQ-5D-5L health utility US index (0.76 [SD, 0.26]; n = 27) and EQ VAS (69.4 [22.3]; n = 28) scores for adults were lower than UK general population norm. By month 36, improvements were seen in EQ-5D-5L health utility US index (mean [SD] change 0.15 [0.15]; MCID 0.078; n = 11), EQ VAS (23.5 [15.9]; MCID 7 to 10; n = 11), FACT-G Total Score (25.3 [25.5]; MCID 3–7; n = 11), BMTS (5.2 [6.7]; MCID 2–3; n = 11) and most ASCQ-Me subscales, including emotional (10.5 [5.5]), social (19.8 [7.7]), and pain (6.9 [8.4]; MCID 5 for all). For ASCQ-Me pain-related subscales, largest improvement was in pain episode frequency (−20.5 [7.2]; MCID −5; n = 11); pain NRS also improved (−1.8 [1.9]; MCID −1; n = 11). For adolescents, EQ-5D-Y VAS improved through month 24 (11.2 [26.6]; n = 6), PedsQL total score improved through month 24 (27.4 [16.8]; MCID 4.36; n = 5), and pain NRS improved (−0.9 [SD, 0.7]; MCID −1; n = 7).

Conclusion: Participants with TDT and SCD infused with exa-cel reported sustained and clinically meaningful improvements in HRQoL across multiple instruments and domains assessed.

1. Locatelli et al. The New England Journal of Medicine, 2024; 390, 1663–1676.

2. Frangoul et al. The New England Journal of Medicine, 2024; 390, 1649–1662.

Topic: 003–Clinical and epidemiological studies

A.N.F. Ayesha Farooqui¹, N.O. Naomi Oravitz², I.R. Insia Rizvi¹, M.F. Marwah Farooqui¹

University of Illinois Chicago¹, Midwestern University²

Cervical cancer is a prevalent malignancy among women globally, with 94% of deaths occurring in developing countries lacking screening guidelines. In the United States, the incidence and mortality significantly decreased over the past 30 years due to proper screening and HPV vaccinations. The American College of Obstetricians and Gynecologists (ACOG) and U.S. Preventive Services Task Force (USPSTF) recommend starting routine Papanicolaou (pap) smear screening at age 21. From ages 21 to 29, a Pap smear with cytology is recommended every 3 years. For women aged 30 to 65, screening options include cytology alone every 3 years, co-testing (cytology and HPV test) every 5 years, or primary HPV testing every 5 years. Screening is not needed after age 65 if no abnormalities were found in the previous 10 years. HPV, a common sexually transmitted infection, is associated with 95% of cervical cancers. Therefore, vaccinations against the high-risk HPV genotypes are recommended for individuals aged 9 to 26 years.

This study examined the prevalence of cervical cancer screening in females with sickle cell disease (SCD), a rare, hematologic disorder affecting about 100,000 people, predominantly Black individuals in the US. Despite advancements in care, the prevalence of HPV and cervical lesions in women with SCD in the US has not been extensively studied.

We conducted a single-institution retrospective chart analysis to determine cervical cancer screening prevalence at our comprehensive care center. Female patients over 21 with clinic visits between January and December 2022 were included, and those who had total hysterectomies were excluded. Data collected included age, HPV vaccination status, age at first Pap smear, pathology from all available Pap smears, intervals between screenings, and HPV test results.

A total of 116 patients met the inclusion criteria. Of these, 68 patients had undergone cervical cancer screening at least once in their lifetime. Only 6 of these 68 patients received the HPV vaccine, an 8.8% HPV vaccination rate. At our center, 58.6% of women with SCD were screened for cervical cancer compared to the national average of 72.4% (71.6% Black) based on CDC reports from 1987 to 2021. Screenings did not occur at recommended intervals. The mean age of individuals who were never screened was 36.3 years, compared to 45.9 years for those who were screened. Table 1 provides additional findings.

Our study indicates that women with SCD are not adequately screened for cervical cancer, with younger females especially less likely to receive routine screening. The Healthy People 2030 target aims to increase cervical cancer screening to 84.3% for women aged 21 to 65 who receive cervical cancer screening to 84.3%, according to the latest USPSTF guidelines, which align closely with ACOG guidelines. Our prevalence is significantly less. Therefore, it is crucial to implement cervical cancer screening and HPV vaccination in the SCD population, which faces numerous barriers to routine preventative care. The HPV vaccine, introduced in 2006, may not have been received by older individuals. Our study, limited to one institution and was conducted post COVID pandemic, may have impacted access to preventative care. Further large-scale studies are needed to determine the exact prevalence of screening, as individuals with SCD are immunocompromised, increasing their risk for cervical cancer due to a reduced ability to clear HPV infections.

1. Cervical cancer. World Health Organization. Published March 5, 2024. Accessed June 15, 2024. https://www.who.int/newsroom/fact-sheets/detail/cervical-cancer#:~:text=Globally%2C%20cervical%20cancer%20is%20the,%2D%20and%20middle%2Dincome%20countries

2. T Mansour, F Limaiem. Cervical Screening. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. https://www.ncbi.nlm.nih.gov/books/NBK537348/

3. American College of Obstetricians and Gynecologists. Updated Cervical Cancer Screening Guidelines. www.acog.org. Published 2021. https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2021/04/updated-cervical-cancerscreening-guidelines

4. MD Chen et al. (eds). Adjuvant Human Papillomavirus Vaccination for Patients Undergoing Treatment for Cervical Intraepithelial Neoplasia 2+. ACOG. Published July 2023. Accessed June 15, 2024. https://www.acog.org/clinical/clinicalguidance/practice-advisory/articles/2023/07/adjuvant-human-papillomavirus-vaccination-for-patients-undergoing-treatment-forcervical-intraepithelial-neoplasia

5. Centers for Disease Control and Prevention, National Center for Health Statistics, National Health Interview Survey, 1987–2021.

6. Office of Disease Prevention and Health Promotion. (n.d.). Increase the proportion of females who get screened for cervical cancer — C-09. Healthy People 2030. U.S. Department of Health and Human Services. https://health.gov/healthypeople/objectives-and-data/browse-objectives/cancer/increase-proportion-females-who-get-screenedcervical-cancer-c-09]

Topic: 003–Clinical and epidemiological studies

A.S.D. Dain¹, Y.L. Li¹, S.M. Master¹, L.R. Raffini¹, K.D.G. Getz¹, J.L.K. Kwiatkowski¹

Children's Hospital Philadelphia¹

Background: Cerebrovascular disease (CVD) is a common cause of morbidity in sickle cell disease (SCD). The impact of modern SCD care on CVD is unknown. The 2014 National Heart, Lung, and Blood Institute (NHLBI) guidelines recommend hydroxyurea (HU) for all patients with SCD-SS and SCD-Sb0 starting at age 9 months, a significant shift from prior. HU protects against CVD progression in those with abnormal or conditional transcranial Doppler ultrasound (TCD); however, the real-world impact of early HU on the initial development of CVD is not well defined. We hypothesize that the 2014 guidelines led to increased HU use and a reduction in incident CVD.

Methods: Subjects with SCD-SS and SCD-Sb0 followed at the Children's Hospital of Philadelphia between 2006–2022 were included in this retrospective cohort study. Exclusion criteria included history of CVD and/or chronic transfusion at study entry. Incident HU in 2011 or later was defined as the first HU prescription in subjects with a minimum of two prescriptions within 1 year. Pre-2011, HU use was manually extracted and coded as a binary (yes/no) variable as prescription dates were not available. The composite outcome of incident CVD includes: abnormal TCD, silent cerebral infarct (SCI), moderate or severe cerebral vasculopathy, or overt ischemic stroke. All MRI and TCD reports were manually reviewed. The proportion of subjects obtaining a brain MRI in each calendar year was calculated annually. Subjects were followed from first hematology visit after 9 months of age until the outcome of interest or censoring (loss to follow up, chronic transfusion, curative therapy, or 8 years of follow up. Ages at HU initiation pre- and post-guideline were compared using the Wilcoxon rank-sum test. Time to CVD was summarized using Kaplan–Meier estimators, with guideline publication incorporated as a time-varying exposure. Associations were calculated with Cox proportional hazard regression.

Results: Final analyses included 701 patients. The proportion of subjects ever prescribed HU increased from 25% in 2011 to 85% in 2022, with an older age at HU initiation before guideline publication (median 7.0 y, IQR 4.2–13.7) vs. after (median 4.5 y, IQR 1.2–8.3, p < 0.001).

Over 3450 person-years of follow-up, 110 incident CVD outcomes occurred, corresponding to a cumulative incidence of 15.7%. MRI screening rates decreased from 33% in 2011 to 13% in 2022 (Fig). In unadjusted analysis, CVD occurrence was significantly lower after guideline publication than before (HR 0.65, 95% CI: 0.44–0.98, p = 0.04). After adjusting for changes in MRI screening over time, the difference in CVD incidence post vs. pre-guideline was attenuated and no longer statistically significant (HR 0.76, 95% CI: 0.36–1.6, p = 0.47).

Summary/Conclusion: After the NHLBI guideline publication, HU prescriptions increased with a younger age at initiation and MRI screening decreased. The ~40% reduction in CVD post-guideline was explained in large part by changes in MRI screening practices, likely related to the concurrent 2014 NHLBI recommendation against MRI screening in asymptomatic children. Our study highlights the importance of rigorous methods to adjust for confounding in analyses of observational data. Determining the relationship between early HU and CVD is important to improve clinical care in patients with SCD. Analyses are ongoing to directly assess the impact of guidelineconcordant HU initiation on CVD.

1. National Heart, Lung, and Blood Institute. Evidence-Based Management of Sickle Cell Disease: Expert Panel, 2014.

2. Ware et al. The Lancet, 2016; 387, 661–670.

3. Hankins et al. The American Journal of Hematology. 2015; 90, 1099–1105.

Topic: 003–Clinical and epidemiological studies

J.M.S. José Manuel Marco Sánchez¹, E.B.C. Eduardo Jesús Bardón Cancho¹, D.B. David Benéitez², S.P.P. Salvador Payán-Pernía³, A.C. Anna Collado⁴, A.R.L. Anna Ruiz-Llobet⁵, J.A.S. José Antonio Salinas⁶, E.S. Elena Sebastián⁷, B.A. Bienvenida Argilés⁸, M.B. Mar Bermúdez⁹, M.A.V. María Ángeles Vázquez¹⁰, M.J.O. María José Ortega¹¹, M.M.P. María del Mar Mañú Pereira¹², P.G. Pablo González¹³, P.V. Perceval Vellosillo¹³, E.C. Elena Cela¹⁴

Hospital General Universitario Gregorio Marañón¹, Hospital Universitario Vall d'Hebrón², Hospital Virgen del Rocío³, Hospi tal Vall d'Hebrón⁴, Hospital Sant Joan de Déu⁵, Hospital Universitari Son Espases⁶, Hospital Niño Jesús⁷, Hospital La Fe⁸, Hospital Virgen de la Arrixaca⁹, Hospital Materno-Infantil Torrecárdenas¹⁰, Hospital Virgen de las Nieves¹¹, Vall d'Hebron Institut de Recerca & Hos pital Universitari Vall d'Hebrón¹², Unidad de Metodología y Bioestadística - Instituto de Investigación Sanitaria Gregorio Marañón (IiSG M)¹³, Hospital Gregorio Marañón¹⁴

Background: The work carried out by REHem-AR researchers continues year after year, providing epidemiological data at national level on hemoglobinopathies and minority anemias. The information collected in this registry promotes the implementation and development of new clinical trials and lines of research in our country. Thus, Spain has become an example of early detection of these diseases at European level, reducing the serious long-term complications of these patients. Furthermore, we have successfully carried out an initial batch transfer of the Spanish registry's baseline patient-level data into RADeep, within the European network Eurobloodnet.

Methods: Observational, descriptive, multicenter and ambispective study, including adult and pediatric patients with hemoglobinopathies and rare anemias registered in REHem-AR, initiated in January 2013 and with annual follow-up. These data correspond to the cross-sectional analysis of February 29, 2024.

Results: Total patients 1934, 80 hospitals. 62% patients <18 years.

− 1398 patients with sickle cell disease (SCD), 77% SS, 14% SC, Sβ0 4.6%. Most diagnosed from neonatal screening (36%) with a median age of 0.9 years (0.1–3.3).

81% (968) received antibiotic prophylaxis, of which 95% are patients under 5 years of age; mainly in SS (778, 80%), median age of onset 0.47 (0.17, 2.78) and with a median duration of 4.2 years (2.3–6.1). 63% (747) received hydroxyurea, median age at onset 5.2 years (2.5–9.8), increasing to 87% focusing on the subgroup of SS patients. 4.5% splenectomized, at a median age of 4.4 years (2.9–8.2).

13% (151) were or are on hypertransfusional regimen, median age at onset 8.0 years (4.0–12.0), of which up to 43% (65) have required chelation therapy, deferasirox as drug of choice and with a median duration of 1.07 (0.67–1.34), similar to the duration of the hypertransfusional regimen. 6.3% have received a hematopoietic stem cell transplantation, 95% of them were SS genotype; currently 66% are in complete chimerism and 28% in mixed chimerism.

204 patients with thalassemia; 129 transfusion-dependent thalassemia (TDT), patients with hemoglobinopathy H were not included inthe NTDT group. Most diagnosed because of anemia (71%) with a median age of 1.0 years (0.0–5.0). 8.8% have been diagnosed in recent years by neonatal screening.

89% of TDT patients have received chelation at some point versus 30% of NTDT patients, median age at onset 2 years (2.0–4.0) and median treatment duration 3.2 years (2.6–7.0). Deferasirox as the iron chelator of choice. 26.5% (54) underwent transplantation, all of them TDT, prevalence of chronic graft-versus-host disease (GvHD) 11% (5 patients) and graft rejection 18%.

The remaining 332 patients were diagnosed with other types of hemoglobinopathies, enzymopathies or other rare anemias; theirclinical and demographic characteristics were also analyzed.

Conclussion: Although the registry began with pediatric patients, the number of centers with registered adult patients is progressively increasing. The rate of loss to follow-up is mainly due to the transfer of patients to their country of origin or to a hospital that does not belong to the REHem-AR network.

1. JM Marco Sánchez et al. Haemoglobinopathies and other rare anemias in Spain: ten years of a nationwide registry (REHemAR). Annals of Hematology, 2024.

2. EJ Bardón-Cancho et al. Spanish registry of hemoglobinopathies and rare anemias (REHem-AR): demographics, complications, and management of patients with β-thalassemia. Annals of Hematology, 2024; 103(5), 1525–1539.

3. EJ Bardón Cancho et al. Update of the Spanish registry of haemoglobinopathies in children and adults. Medicina Clínica (Barc), 2020; 155(3), 95–103.

4. FB Piel et al. Sickle cell disease. The New England Journal of Medicine, 2017; 376(16), 1561–1573.

5. LG Weil et al. Sickle cell disease and thalassaemia antenatal screening programme in England over 10 years: a review from 2007/2008 to 2016/2017. The Journal of Clinical Pathology. 2020; 73(4), 183–190.

6. CC Hoppe. Prenatal and newborn screening for hemoglobinopathies. International Journal of Laboratory Hematology, 2013; 35(3), 297–305.

Topic: 003–Clinical and epidemiological studies

N.K.D. Devi¹

University of Delhi¹

Background: Beta thalassemia, is one of the most common monogenic blood disorders. Globally the prevalence of beta thalassemia carriers is 1.5%. India contributes to 10% of the incidence of beta thalassemia major, and 3.74% of the Indian population are carriers. However, pertaining to the heterogeneity in Indian population in terms of diverse gene pool with different socio-cultural practices, determination of a cost-effective screening strategy is essential. In India, majority of the studies conducted were community-specific, and most studies reported that 5 common mutations (IVS 1-1 (G>T), 619 bp deletion, IVS 1-5 (G>C), Cd 41/42, Cd 8/9) are primarily responsible for Beta thalassemia trait in India.

Aim: The present study aims to explore the mutation spectrum of beta thalassemia trait in a heterogenous population in Delhi NCR, India, and identify an accurate cost effective cut off based on blood parameters for the screening of beta thalassemia trait in India.

Methods: The study recruited 3600 individuals aged 18–35 years, who were residing in Delhi NCR, India. Blood samples were collected from the participants in EDTA vacutainers by trained phlebotomists. The samples were analysed for Beta thalassemia trait, using CBC analysis followed by HPLC and molecular characterization, which included ARMS PCR, and gene sequencing.

Results: The study revealed that the most ideal cut off to identify beta thalassemia carriers using blood parameters is 3.2% ≤ HbA2 ≥ 3.8% and MCV <80fl and MCH < 27 pg or 3.9% ≤ HbA2 ≥ 9%. This cut off adequately covers the border line HbA2 cases of beta thalassemia trait as well. Meanwhile, the most frequent mutation was IVS 1–5 among the studied population, followed by Cd 8/9, and Cd 41/42.

Conclusion: Though genetic analysis through HBB gene sequencing is the most efficient screening test for BTT, it is expensive and often not affordable in large scale screening programs, especially in developing countries with high burden of the disease. Hence accurate identification of carriers through cost effective techniques, and further promotion of awareness can be the most effective preventive strategy for control of beta thalassemia burden.

Topic: 003–Clinical and epidemiological studies

A.T. Taher¹, H. Al-Samkari², Y. Aydinok³, M. Besser⁴, J.L. Dahlin⁵, G. De Luna⁶, J.H. Estepp⁵, S. Gheuens⁵, K.S. Gilroy⁵, A. Glenthøj⁷, A.S. Goh⁸, V. Iyer⁵, A. Kattamis⁹, S.R. Loggetto¹⁰, S. Morris⁵, K.M. Musallam¹¹, K. Osman⁵, P. Ricchi¹², E. SalidoFiérrez¹³, S. Sheth¹⁴, F. Tai⁵, H. Tevich⁵, K. Uhlig⁵, R. Urbstonaitis⁵, V. Viprakasit¹⁵, M.D. Cappellini¹⁶, K.H.M. Kuo¹⁷

American University of Beirut Medical Center¹, Massachusetts General Hospital, Harvard Medical School², Ege University School of Medicine³, Cambridge University Hospitals NHS Foundation Trust⁴, Agios Pharmaceuticals, Inc.⁵, Hôpital Henri Mondor APHP⁶, Copenhagen University Hospital-Rigshospitalet⁷, Hospital Pulau Pinang⁸, National and Kapodistrian University of Athens⁹, Sao Paulo Blood Bank-GSH Group¹⁰, Burjeel Medical City¹¹, Azienda Ospedaliera di Rilievo, Nazionale, Cardarelli¹², Hospital Clínico Universitario Virgen de la Arrixaca-IMIB¹³, Weill Cornell Medicine¹⁴, Siriraj Hospital, Mahidol University¹⁵, University of Milan, Ca' Granda Foundation IRCCS Maggiore Policlinico Hospital¹⁶, University of Toronto¹⁷

Background: In thalassemia, ATP production in erythroid cells is insufficient to meet increased demand resulting from unpaired globin chain precipitation and oxidative damage, leading to ineffective erythropoiesis (IE) and chronic hemolytic anemia.^1–3 Guidelines for non–transfusion-dependent β-thalassemia (β-NTDT) recommend raising hemoglobin (Hb) by ≥1 g/dL to reduce morbidities linked to IE and anemia.⁴ No oral disease-modifying therapies are approved for β-thalassemia, and none are approved for α-thalassemia. Mitapivat is an oral activator of pyruvate kinase that increases ATP production.^5,6 Mitapivat may decrease metabolic stress, addressing the underlying pathophysiology across the full range of thalassemias, with potential to reduce complications and improve health-related quality of life (HRQoL).

Aims: To assess the efficacy and safety of mitapivat versus placebo (PBO) in adults with α- or β-NTDT in ENERGIZE (NCT04770753), a phase 3, double-blind, randomized, global trial.

Methods: After providing informed consent (IC), adults (≥18 years) with α- or β-NTDT and baseline (BL) Hb ≤10 g/dL were randomized 2:1 to mitapivat 100 mg twice daily or PBO for 24 weeks (wks). NTDT was defined as ≤5 red blood cell (RBC) units transfused 24 weeks before randomization and no RBC transfusions ≤8 weeks before IC or during screening. The primary endpoint was Hb response (defined as ≥1.0 g/dL increase in average Hb concentration over Wks 12–24 compared with BL). Key secondary endpoints were changes from BL in Functional Assessment of Chronic Illness Therapy–Fatigue Scale (FACIT-Fatigue) and average Hb concentration score over Weeks 12–24. Safety and markers of hemolysis and erythropoiesis were among the secondary endpoints.

Results: Of 194 patients (pts) randomized to mitapivat (N = 130) or PBO (N = 64), 94.8% completed the study. BL characteristics were balanced across treatment arms; mean age was 41.2 years, mean Hb was 8.3 g/dL, 86.6% received no transfusions in the 24 weeks before randomization, and 32.0% had α-NTDT.

Hb response was significantly improved with mitapivat versus PBO (42.3% vs. 1.6%, respectively; 2-sided p < 0.0001 [Figure]). Mitapivat also demonstrated significant changes from BL in Weeks 12–24 average FACIT-Fatigue score (least-squares mean [LSM] difference (95% CI): 3.40 (1.21, 5.59); 2-sided p = 0.0026) and Weeks 12–24 average Hb (LSM difference (95% CI): 0.96 g/dL (0.78, 1.15); 2-sided p < 0.0001). Results were favorable for mitapivat versus PBO across all prespecified subgroups. Improvements in several markers of hemolysis and erythropoiesis were observed, consistent with the proposed mechanism of mitapivat.

The incidence of any-grade treatment-emergent adverse events (TEAEs) was balanced between mitapivat (82.9%) and PBO (79.4%). The most common TEAEs (≥10% of pts) with mitapivat were headache, initial insomnia, nausea, and upper respiratory tract infection. Among mitapivat-treated pts, 6.2% had serious TEAEs (none considered treatment related) and 3.1% had TEAEs leading to treatment discontinuation; none occurred with PBO.

Summary/Conclusion: Mitapivat significantly improved Hb and fatigue versus PBO; improvements were observed across all prespecified subgroups. Mitapivat was well tolerated with few treatment discontinuations. This is the first proof-of-efficacy of a disease-modifying therapy across the full range of NTDT (α- and β-thalassemia). Mitapivat may represent a new oral treatment option addressing both pathophysiology and HRQoL in thalassemia.

1. Chakraborty et al. Archives of Medical Research, 2012; 43, 112.

2. Ting et al. British Journal of Haematology, 1994; 88, 547–554.

3. Sanchez-Villalobos et al. Frontiers Media (Lausanne) 2022; 9, 880752.

4. Taher et al. In: Nicosia (Cyprus): Thalassaemia International Federation 3rd ed.; 2023. www.ncbi.nlm.nih.gov/books/NBK599489/. Accessed 22 May 2024.

5. Kung et al. Blood, 2017; 130, 1347.

6. Yang et al. Clinical Pharmacology in Drug Development 2019; 8, 246.

Topic: 003–Clinical and epidemiological studies

D.R. Jigeesha Das¹, D.R. Pradyumna Kumar Dash¹, D.R. Sudha Sethy¹, D.R. Rabindra Kumar Jena¹, D.R. Manmohan Biswal¹

SCB Medical College and Hospital, Cuttack¹

Background: Thalassemia is a group of disorders, belonging to hemoglobinopathies, each resulting from an inherited abnormality in production of globin moiety of hemoglobin. Although the standard therapy is regular blood transfusion, hydroxyurea, folic acid along with other supportive therapy, the only curative treatment available is hematopoetic stem cell transplantation. Regular blood transfusion can sustain growth and development for upto a decade of life yet the resultant iron overload ultimately restricts children's physical and sexual growth and also negatively affects cardiovasular, gastrointestinal and endocrine systems. Chronic blood transfusions also increases risk of Transfusion Transmitted Infections. Because of difficulties in access to bone marrow transplant services,safe blood in developing nations research has led to discovery of alternate therapies. Thalidomide has shown promising results in reducing transfusion requirements with acceptable adverse events such studies are limited in pediatric age groups in India.

Aim: To estimate beneficial effects of addition of Thalidomide to standard therapy (non-transplant) in transfusion-dependent thalassemia (Beta thalassemia homozygous).

Methods: This is a prospective observational study which includes all the transfusion dependent beta thalassemia patients more than 4 to 18 years of age.These patients required frequent transfusions despite standard therapy. The study had been conducted in Department of Clinical Hematology, SCB Medical College and Hospital, Cuttack after taking ethical committee permission and written informed consent from parents/guardians in between January 2023 to January 2024. Inclusion Criteria: 1. Diagnosed case of transfusion dependant thalassemia (TDT) Beta Thalassemia Major (1–3 packed red blood cell transfusion/month) 2. More than 4 years of age 3. Participants in whom bone marrow transplant was not an option. Exclusion Criteria: 1. Cardiopulmonary, Cerebrovascular, seizure disorder, gastrointestinal and renal disorders, malignancy and any other severe diseases. 2. Thrombocytopenia, neutropenia. 3. Allergy to drugs.

Baseline characteristics, blood transfusion history, and complete blood count, hemoglobin electrophoresis (HPLC), urea, creatinine, and liver function tests along with liver and spleen size (clinically and by ultrasonography) were recorded at baseline, third month, and sixth month and 1 year of follow up of thalidomide therapy. All patients had recieved tab thalidomide 2–3 mg/kg along with iron chelation therapy- Tab Deferasirox (20–40 mg/kg) and all other supportive therapy.

Primary End point: Reduction of transfusion requirements by 25% at the end of 6 months of treatment. Secondary End point: Reduction of liver size, spleen size by 30%, serum ferritin level by 500 ng/mL, and increase in hemoglobin by 1 g/dL at the end of 6 months of therapy.

Response assesment: Good response: Hemoglobin maintained >10 g/dL without packed red blood cell transfusion. Partial response: Minimum 25% reduction in transfusion requirements. No response: No change in transfusion requirements or less than 25% reduction in transfusion.

Result: Analysis was done after 6 months and 1 year of thalidomide therapy and compared with baseline value. 19 patients showed non compliance to therapy hence excluded from the study and not analysed. Total patients enrolled: n = 116. Duration of thalidomide therapy for 6 months: n = 84 (72.4%), for 1 year n = 32 (27.6%). M:F ratio-20:9. Primary end point achieved: n = 96 (82.8%), Secondary end point achieved: Reduction in liver size by 30%: n = 74 (63.7%), Reduction in spleen size by 30%: n = 78 (67.2%), Reduction in ferritin level by 500 ng/mL: n = 88 (75.8%), Increase in hemoglobin by 1 gm/dL: n = 84 (72.4%). Response assessment: Good response: n = 28 (24.1%), partial response: n = 68 (58.6%), no response: 20 (17.2%). The median time response to thalidomide tharapy was 5 months. Duration between transfusion, fetal hemoglobin (HbF), hemoglobin increased significantly (p < 0.001), and transfusion volume, liver size, spleen size, serum ferritin reduced significantly (p < 0.001) at 6 months and 1 year of therapy. Out of 116 patients constipation, sedation, rashes, diarrhea were main adverse effects and were managed with standard protocol.

Conclusion: Addition of thalidomide to the standard therapy is beneficial by achieving primary end point (25% reduction in transfusion requirement) in 82.8% cases at the end of 6 months of treatment. Adverse reaction were seen in 40% cases which were mild to moderate in nature and managed with supportive tharapy.

1. SH Ansari et al. Evaluation of the combination therapy of hydroxyurea and thalidomide in beta thalassemia. Blood Advances, 2022; 6(24), 6162–6168.

2. P Mehta et al. Experience with low dose thalidomide in transfusion dependent beta thalassemia in resource limitited setting. Blood, 2019; 134, 963.

Topic: 003–Clinical and epidemiological studies

R. Muzambi¹, D. Dexter², G. Sathyamoorthy¹, A. Bottle¹, C. Reynolds³, F. Piel¹

Imperial College London¹, Princess Royal Univeristy Hospital, King's College Hospital NHS Foundation Trust,² NHS Race and Health Observatory³

Background: Recent reports, including a UK parliamentary inquiry, have identified insufficient funding for sickle cell disease (SCD) research. (1) While studies in the United States have reported research funding disparities between SCD and cystic fibrosis (CF), comparable evidence in the UK is lacking.

Aim: To compare SCD research funding, and funding related outputs such as registered clinical trials and research publications with those for other inherited conditions in the UK.

Method: We analysed publicly available data on indicators of inequality for SCD compared with CF and haemophilia. We selected indicators of inequality related to funding that included research grants from main UK funders and resources available to dedicated UK charities, registered clinical trials, and scientific publications. We searched a wide range of sources including the National Institute of Health Research (NIHR), UK research and Innovation (UKRI) and Wellcome Trust websites, the National Haemoglobinopathy Register, The CF Trust Registry, the National Haemophilia Database, the National Library of Medicine Clinical Trials, and Pubmed. We calculated the average annual funding per person using the number of patients reported in 2022 in the patient registries for the three conditions.

Results: Between 1st January 2010 and 31st December 2023, 73.6% of the total projects funded by NIHR, UKRI and Wellcome for SCD, CF and haemophilia were allocated to research related to CF, amounting to £107.3 million; funding for SCD totalled £40.8 million and for haemophilia £34.3 million. Accounting for the number of people with each condition, the average annual funding per person was lowest for SCD at £184, compared with £688 for CF and £224 for haemophilia. Research publications in PubMed over the same 14-year study period were also highest for CF (n = 34,594), which had almost double the number of research articles compared with SCD (n = 18,757) and haemophilia (n = 16,560). In terms of clinical trials, SCD had the lowest number of clinical trials with a UK centre between 2010 and 2023 at 14.3%, compared with 50.9% for CF and 34.8% for haemophilia. Disparities in resources available from dedicated UK charities in the financial year 2022–2023 were also striking, with the CF Trust receiving almost twenty times more income (£14.7 million) than the Sickle Cell Society (£773,597) or the Haemophilia Society (£795,226).

Conclusions: SCD attracts less research attention and funding than both haemophilia and particularly CF. This may contribute to the neglect, poor awareness and inadequacies in the care and management of SCD previously documented. Evidence-based policy recommendations are needed to reduce these inequalities and provide a better quality of life for all patients affected by severe chronic genetic conditions.

1. All Party Parliamentary Group on Sickle Cell and Thalassaemia, Sickle Cell Society. No one's listening: an inquiry into the avoidable deaths and failures of care for sickle cell patients in secondary care. 2021.

Topic: 003–Clinical and epidemiological studies

C. Ginete¹, M. Brito¹, M. Delgadinho¹, C. Cruz¹, M. Mendes², F. Simão², J.N. Vasconcelos³

Health and Technology Research Center, Escola Superior de Tecnologia da Saúde de Lisboa, Instituto Politécnico de Lisboa¹, Maternidade Lucrécia Paim², CISA–Centro de Investigação em Saúde de Angola³

Background: The prevalence of sickle cell disease (SCD) in Angola can reach 2%, and the number of pregnant women with SCD is very high. Pregnancy in SCD poses a risk of severe complications, including eclampsia, pre-eclampsia, strokes, and even mortality in mother an in the fetus. Therefore, it is of utmost importance to maintain continuous medical surveillance throughout pregnancy.

Aims: The study aimed to identify pregnancy complications in women with SCD between June 2021 and March 2024, with a particular focus on factors contributing to maternal mortality at Lucrecia Paim Maternity Hospital, Luanda, Angola., and associated with genetic variability.

Methods: Pregnancy monitoring included analysis of clinical history and incidents (number of hospitalizations, blood transfusions, occlusive painful crisis, and other clinical complications), hematological and biochemical analysis and genetic analysis. We genotyped four SNPs in the β-cluster to assess the haplotype, evaluated the presence of the 3.7 kb deletion of the α-globin gene, and analyzed SNPs in BCL11A, rs1427407 (G>T), and HIC2 gene, rs80230662 (C>T) and rs77362533 (C>T).

Results: A total of 203 women were followed, however so far, only for 125 the complete results were obtained. Ages ranged from 17 to 46 years old (with a median age of 25.0 ± 5.7). Among the patients, 76.5% have previously received blood transfusions (75 out of 98), 95.9% have been hospitalized (94 out of 98) due to complications from SCD, and 21.8% (22 out of 101) have experienced at least one miscarriage. Regarding the genetics, the most prevalent haplotype in this population is the CAR/CAR haplotype (67.2%), which is typically associated with a more severe prognosis. The CAR/Atypical haplotype follows in prevalence at 12.8%. Additionally, 8.8% of the population is homozygous for the 3.7 kb thalassemia deletion, while 46.4% are carriers. This deletion has an impact on the hematological and clinical characteristics of SCD patients, resulting in less severe phenotypes.

Preliminary results indicate significant impacts of co-inherited alpha-thalassemia haplotypes on hematological values. Homozygous individuals for the 3.7 kb deletion exhibited significantly lower mean corpuscular volume (MCV: 69.53 ± 18.66 fL vs. 86.60 ± 13.20 fL; p = 0.01), mean corpuscular hemoglobin (MCH: 25.05 ± 3.13 pg vs. 30.25 ± 4.50 pg; p = 0.01), and mean corpuscular hemoglobin concentration (33.50 ± 1.67 vs. 36.00 ± 1.20 g/dL; p = 0.01). This likely attenuated hemolysis/anemia, as evidenced by higher RBC count (3.17 ± 0.83 vs. 2.44 ± 0.57 × 10⁶/µL; p = 0.01) and hematocrit levels (HCT 23.67 ± 3.47 vs. 20.45 ± 4.21%; p = 0.01). Alphathalassemia homozygotes also had lower total bilirubin levels (0.62 ± 0.66 vs. 1.30 ± 1.31 mg/L; p = 0.10) and fewer transfusions (p = 0.03), with no individual requiring more than five transfusions. Pregnancy outcomes improved significantly, with perinatal survival rates at 83.3% for homozygotes, compared to 40.6% for heterozygotes and 57.7% for those without the deletion (p = 0.03).

Regarding haplotypes, the CAR/CAR group displayed worse hematological indices with lower HCT (20.20 ± 3.51 vs. 22.40 ± 4.84%), hemoglobin (HGB) (7.00 ± 1.08 vs. 8.00 ± 1.46 g/dL), and RBC counts (2.57 ± 0.57 vs. 2.81 ± 0.81 × 10⁶/µL) levels compared to other haplotypes. They also exhibited higher platelet counts (326.28 ± 164.34 vs. 243.50 ± 125.74 × 10³/µL; p = 0.03) and the highest leukocyte counts (11.97 ± 7.94 vs. 9.64 ± 4.53 × 10³/µL; p = 0.04), indicators of hemolysis and chronic inflammation, as well as a greater propensity for pain crises (p = 0.02). Despite these results, there was no significant worsening of pregnancy outcomes (p = 0.15), although the results suggested a trend towards a lower percentage of perinatal survival with the inheritance of this haplotype (50.0%) compared to the others (36.8%).

We also analyzed the SNP rs1427407 (G>T) located in the BCL11A gene, as well as the SNPs located in the HIC2 gene, rs80230662 (C>T) and rs77362533 (C>T). Despite a significant increase in MCV (102.9 ± 19.05 vs. 84.50 ± 1.33 fL; p = 0.03), MCH (31.86 ± 5.18 vs. 29.30 ± 4.61 pg; p = 0.03) in rs1427407 T homozygous individuals, no significant values were obtained concerning the severity of SCD or its impact on pregnancy outcomes. Similar results were observed for SNPs rs80230662 and rs77362533, which also did not show significant impacts.

Conclusion: These findings have the potential to positively impact medical care for this vulnerable population, reducing risks and improving obstetric outcomes in pregnant women with SCD, not only in Angola but also in other resource-limited settings.

1. Arkuszewski et al. American Journal of Neuroradiology, 2011, 32(8), 1444–1450.

2. Boafor et al. BJOG: An International Journal of Obstetrics & Gynaecology, 2016, 123(5), 691–698.

3. Borges et al. Hemoglobin, 2019, 43(3), 149–154.

4. Hussain et al. Pediatric Blood and Cancer, 2015, 62(2), 219–223.

5. Muganyizi and H Kidanto. PLoS ONE, 2013, 8(2).

6. Santos et al. Molecular Biology Reports, 2020, 47(7), 5397–5402.

Topic: 003–Clinical and epidemiological studies

F.B. Bernaudin¹, C.A. Arnaud², A.K. Kamdem², I.H. Hau³, C.D. Delestrain³, C.J. Jung⁴, R.E. Epaud³, S.V. Verlhac²

Clinical Research, Referral Center for SCD¹, Referral Center for SCD², Pediatrics³, Clinical Research Center⁴

Background: Randomized trials demonstrated the efficacy of hydroxyurea (HU) to reduce the rate of crises, and transfusion needs in patients with sickle cell anemia (SCA) in high/low income countries. However, the effect of HU on silent cerebral infarcts (SCI) prevention remains unclear

Aims: To describe/analyze the impact of HU, chronic-transfusion (CT), and allogeneic stem cell transplantation (alloSCT) on SCI-incidence in a SCA-cohort of patients all assessed for intra- and extracranial arteriopathy.

Methods: In SCA-children followed at referral center in Créteil, the extracranial part of internal carotid artery (eICA) was routinely added since June-2011 using color-Doppler ultrasound, and neck-MRA. CT was applied for intracranial or eICA time-averaged mean maximum velocity (TAMMV) ≥200 cm/s or frequent complications despite HU. AlloSCT was recommended for cerebral vasculopathy or complications despite HU to those with HLA-identical sibling HU, not systematically given in this cohort was prescribed for frequent crises, acute chest syndromes, baseline Hb <7 g/dL or abnormal TAMMV history (≥200 cm/s) after normalization and no stenosis and in patients with eICA-TAMMV 160–199 cm/s without stenosis when not already given.

Results: All 332 stroke-free SCA-children (1992–2014), longitudinally assessed for MRI/MRA/neck-MRA were included in the study, data were updated in July-2019.

HU was administered to 239 (72.0%) (Figure A). CT initiated in 231 (69.6%) patients and alloSCT performed in 60 (18.1%) SCA-patients.

Intracranial arteriopathy, defined by intra-TAMMV ≥ 200 cm/s or stenosis was present in 108 (32.5%); eICA arteriopathy, defined by eICA-TAMMV ≥ 160 cm/s or eICA stenosis in 52 (15.7%) while 172 (51.8%) had no arteriopathy. SCI was detected in 63 patients including 16/52 (30.8%) with eICA-arteriopathy, 22/108 (20.4%) with intracranial arteriopathy, and 25/172 (14.5%) with no arteriopathy (Khi2, p = 0.029). SCI incidence during MRI-follow-up (3853 patient-years) was 1.6 per 100 patient-years. KM-estimated (95% CI) cumulative risk of SCI was 25.0% (19.0%–31.0%), by age 14 (Figure B) significantly lower than reported in the previous cohort never eICAassessed: 37.4% (26.3-50.%) (Log-Rank, p = 0.003). eICA-arteriopathy was significantly associated with the highest SCI-risk (Figure C).

Logistic regression analysis showed that abnormal-TCD, intracranial stenosis, age at HU initiation were not associated with SCI-risk while age at first neck-MRA | OR = 1.1 per 1 year increase (95% CI: 1.0–1.2), p = 0.001] and isolated eICA-TAMMV ≥ 160 cm/s |OR = 3.6 (95% CI: 1.7–7.5), p = 0.001], were strongly significant, independent risk factors for SCI Initiation of HU before age 6 was significantly associated with a reduction in abnormal TCD-incidence (Log-Rank, p = 0.007) (Figure D) but the reduction of abnormally high eICA-TAMMV incidence was not significant (Figure E) and SCI incidence was not different (Figure F).

The incidence of silent strokes per 100 patient-years was 2.2 on HU compared to 0.3 on CT while after allogeneic SCT, no patient developed SCI.

In patients on hydroxyurea, high MCV, low hemoglobin, and high leukocyte count were independent significant risk factors for SCI.

Summary/Conclusion: In the present cohort-study, HU was associated with intracranial arteriopathy prevention but not with eICA-arteriopathy and SCI prevention rendering impact of HU on SCI still unclear. High MCV being risk factor for SCI on HU, drugs improving hemolytic anemia without increasing MCV could perhaps reduce SCI-risk.

1. MR DeBaun et al. Blood Advances. 2020; 4(8), 1554–1588.

2. RJ Adams et al. The New England Journal of Medicine, 1998; 339, 5–11.

3. F. Bernaudin et al. Blood, 2011; 117(4), 1130–1140; quiz 1436

4. PT Telfer et al. Blood, 2011, 118, 6192–6199.

5. S Verlhac et al. Pediatric Radiology, 2014; 44(5), 587–596.

6. F Bernaudin et al. Blood, 2015, 125, 1653–1661.

7. MR DeBaun et al. The New England Journal of Medicine, 2014; 371(8), 699–710.

8. WC Wang et al. Lancet, 2011; 377(9778), 1663–1672.

9. S Verlhac. Tutorial: Doppler ultrasound and sickle cell anemia, 2023. https://1drv.ms/f/s!ArjMYFO2uwGBpDRfEIh197cwamp7?e=vnwRJr

Topic: 003–Clinical and epidemiological studies

J.J. John James¹, B.A. Biree Andemariam², J.M. Johnny Mahlangu³, R.C. Raffaella Colombatti⁴, J.W. John Waller⁵, S.A. Samar Al-Behaisi⁵, A.W. Adam Wufsus⁶, G.M. Gareth Morrell⁷, C.T. Cassandra Trimnell⁸

Sickle Cell Society¹, University of Connecticut Health², University of the Witwatersrand³, University of Padova⁴, Novo Nord isk Health Care AG⁵, Novo Nordisk Inc.⁶, Madano⁷, Sickle Cell 101⁸

The LISTEN Survey was fully funded by Novo Nordisk. Novo Nordisk employees input into the survey design and content and are co-authors of this abstract.

Background: The success of clinical trials of new therapies for sickle cell disease (SCD) depends on recruiting and retaining a large and diverse group of people with SCD (PwSCD). The Learnings and Insights into Sickle Cell Trial Experiences (LISTEN) Survey was developed to understand the global barriers and motivators to participation in clinical trials for PwSCD.¹

Aims: To present findings from the LISTEN Survey regarding clinical trial experience of PwSCD, barriers and motivators to participation, and differences in perspectives between PwSCD and healthcare professionals (HCPs) treating PwSCD.

Methods: From 6 October 2022 to 22 August 2023, PwSCD (≥18 years) and HCPs involved in the treatment of PwSCD in 17 countries completed quantitative surveys. PwSCD were asked about prior participation in clinical trials and whether their experience met their expectations. PwSCD rated the importance of factors (grouped into five categories) that may affect their decision to participate in a clinical trial on a 7-point scale (from not at all to extremely important) and ranked them from most to least important. HCPs provided their perspectives on the importance of these factors to PwSCD.

Results: Overall, 1145 PwSCD (58% female) with a median age of 30 years, and 361 HCPs (67% haematologists or SCD specialists) completed the survey. One-third (n = 373) of PwSCD had been invited to participate in a clinical trial for SCD. Of the 22% who had taken part, most (71%; n = 181/256) described their experience as the same or better than expected. Extremely or very important factors that motivated PwSCD to participate in a clinical trial included the potential to better manage their symptoms (50%), the opportunity to try a new treatment that might work better (50%), and to increase their knowledge of SCD (50%; Figure). An important barrier to participation was the potential to experience different side effects (51%). Regarding trial information, PwSCD ranked (first or second of five) safety measures (56%) and how the treatment works (48%) as the most important factors. Regarding further considerations, PwSCD ranked (first or second of five) speaking to other PwSCD involved in the trial (49%) and experts running the trial (50%) as the most important factors. HCPs overstated the importance of potential practical barriers for PwSCD compared with responses from PwSCD, including missing school/work (50% vs. 41%; p = 0.003), additional effort or planning to start the trial treatment (45% vs. 33%; p < 0.001) and travel requirements (52% vs. 37%; p < 0.001). HCPs understated the importance of wider impact and outcomes of a trial for motivating PwSCD compared with responses from PwSCD, including supporting new treatment developments that may benefit them (41% vs. 49%; p = 0.008) or other PwSCD (38% vs. 48%; p < 0.001).

Summary/Conclusion: Improving access and recruitment into clinical trials in SCD will require potential benefits to individuals and the wider SCD community to be clearly communicated, as well the anticipated safety profile. Findings from the LISTEN Survey highlight that those directly involved in the trial, including other PwSCD, should communicate these messages. Accounting for the disconnect between PwSCD and HCPs, shared decision-making may also improve understanding and increase participation in clinical trials.

Data from this abstract were presented at the 65th ASH Annual Meeting, 9–12 December 2023, San Diego, USA; Poster 2498

Topic: 003–Clinical and epidemiological studies

U. Boccadifuoco¹, I. Lerner², G. Cheminet¹, J.B. Arlet¹

Internal Medicine, European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris¹, Public Health and Informatics Department, European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris²

Background: Recent in vitro studies have suggested a certain degree of dyserythropoiesis in sickle cell disease (SCD) and a significant role of haemoglobin F (HbF), which helps rescue the abortion of late erythroblasts in the bone marrow.¹ Circulating erythroblasts (cEB) in the peripheral blood of patients with SCD may be detected in acute situations (such as vaso-occlusive events (VOE)), or at steady state. In this latter context, the significance of their presence largely is unknown.

Aims: Our objective was to compare clinical and biological characteristics of adult patients with SCD depending on the presence or not of cEB at steady state.

Methods: We conducted a monocentric, retrospective, observational study involving patients ≥18 years with SCD (all genotypes) followed in a French National Referral Centre. Patients were included if they had at least two visits (with a minimum interval of 3 months) with a biological assessment comprising a complete blood count (CBC), at steady state (consultation or day hospital), between 01/01/2017 and 31/07/2023. Two groups of patients were defined: presence (cEB+) or absence (cEB−) of cEB (threshold: 1/100 leukocytes) at inclusion (defined as the time of the first blood test in the considered period). Patients who received a transfusion in the past 3 months, or a bone marrow transplantation, were excluded. Data were extracted from the hospital's clinical data warehouse using targeted structured query language (SQL) queries (2). The diagnosis of hospitalized vaso-occlusive crisis (HVOC) was determined based on the presence of the ICD-10 code D57.0. Clinical and biological characteristics at inclusion, and the incidence of new VOE were compared between groups using Kruskal–Wallis rank sum test for continuous variables, Pearson's Chi-squared test for categorical variables, and trend test for ordinal variables. Time to new VOE was analysed using Kaplan–Meier curves, difference between groups were tested using the log-rank test. Statistical analyses were made using R version 4.0.3.

Results: We included 384 patients with a median age of 26 [19.5;34.1] years: 201 (52.3%) women, 278 (76.8%) with HbSS, 60 (16.6%) with HbSC, 9 (2.5%) with HbS/β⁰-thalassemia, and 15 (4.1%) with HbS/β⁺-thalassemia genotype, respectively. No intergroup difference was observed concerning median age, sex ratio or rate of chronic complications. As compared to the cEB- group, at inclusion, patients in the cEB+ group (n = 212, 55.2%) more often had a history of ≥1 acute chest syndrome (ACS) (158/212 (74.5%) vs. 100/172 (58.1%), p < 0.001) and had more often the HbSS or HbS/β⁰-thalassemia genotype (184/212 (86.7%) vs. 103/172 (66.9%)). Patients with cEB had a lower haemoglobin (Hb) level (8.9 [7.9;10.1] vs. 9.9 [9.0;11.3] g/dL, p < 0.001), a higher mean corpuscular volume (MCV) (88.5 [79;98] vs. 79 [70;89] fL, p < 0.001), a higher reticulocyte count (224 [149;307.5] vs. 160.5 [112.5;242] G/L, p < 0.001) and a higher ferritin level (136 [55;287] vs. 58 [32;168], p < 0.001). Also, significantly higher lactate dehydrogenase level, total bilirubin level, and estimated glomerular filtration rate (eGFR) were observed in the cEB+ group: 378 [292;504] vs. 320 [250;425] UI/L, p < 0.001; 41 [25;67] vs. 29 [19.8;46.2] µmol/L, p < 0.001; 132.8 [118.6;143.5] vs. 126.1 [110.4;136.5] mL/min/1.73 m², p = 0.003, respectively. During follow-up, the time to new HVOC (median 0.89 (cEB+ group) vs. 1.61 (cEB− group) years), ACS, or priapism was significantly shorter in the cEB+ group (p = 0.0069; p = 0.0024; p = 0.000 72, respectively).

In the HbSS and HbS/β⁰-thalassemia population subset (n = 284), patients in the cEB+ group (n = 182, 64%) had no specific clinical features but a significantly lower Hb level (8.7 (7.7;9.8) vs. 9.3 [8.4;10] g/dL, p = 0.043), a higher MCV (90 [81;99] vs. 85 [78;92] fL, p = 0.014) and a higher ferritin level (150 [62;305.8] vs. 73 [36;254] µmol/L, p = 0.048). No significant differences concerning reticulocyte counts, markers of haemolysis, hydroxyurea use, β-globin haplotype distribution, or prevalence of alpha-thalassemia were observed.

During follow-up in this subset, only the time to a new priapism event was significantly shorter in the cEB+ group (p = 0.037).

Conclusion: The presence of circulating erythroblasts in adult patients with SCD appears as a frequent feature (more than half of patients), and is associated with lower Hb level, higher MCV, and more frequent priapism events. Other studies are needed to better characterize these circulating erythroblasts, and to investigate whether they are potentially associated with dyserythropoiesis in this population.

1. El Hoss et al. Haematologica, 2021; 106(10), 2707–2719.

2. Jannot et al. International Journal of Medical Informatics, 2017, 102, 21–28.

Topic: 003–Clinical and epidemiological studies

M. Bruinooge ¹, M.E. Houwing ¹, S.A.M. Teuben ¹, M.H. Cnossen ¹

Department of Paediatric Haematology and Oncology, Erasmus MC Sophia Children's Hospital, University Medical Centre Rotterdam¹

Background: The National Heart, Lung, and Blood Institute (NHLBI) guidelines recommend initiation of hydroxyurea in all children ≥9 months old diagnosed with HbSS and HbSβ0 sickle cell disease regardless of clinical severity. Despite these recommendations and conclusive evidence on its efficacy, safety, and cost-effectiveness in both children and adults, underutilisation of hydroxyurea in clinical practice persists.

Aims: The primary aim of this study was to support the prescription of hydroxyurea to paediatric patients with sickle cell disease using a health literacy-based decision-making tool, and to collect data on caregiver- and patient-related barriers for the use of hydroxyurea in children with sickle cell disease. The secondary aim was to provide an example of a health literacy-based decision-making tool for clinical practice.

Methods: A health literacy-based shared decision-making tool was created (Figure 1). This tool was used by healthcare professionals during shared decision-making consultations with patients ≥12 years old and caregivers of patients ≥9 months diagnosed with HbSS and HbSβ0 sickle cell disease, to discuss hydroxyurea initiation. Data were collected on patient and caregiver characteristics, reasons for not initiating hydroxyurea treatment, and satisfaction with the shared decision-making process measured using the effective decision-making subscale of the decisional conflict scale.¹

Results: This study enrolled 30 caregivers of 33 children. Among these children were two patients ≥12 years old who participated in the consultation and decision-making process. The mean age of children was 5.6 years old (±4.0 SD). All patients except one (97%) were diagnosed with homozygous HbSS sickle cell disease. The mean age of caregivers was 33.6 (±9.6 SD); most were female (80%). Twenty-five out of 30 caregivers (83%) and both children ≥12 years old participating in the decision-making process, decided to initiate treatment with hydroxyurea. The mean score on the effective decision-making subscale of the decisional conflict score in those deciding to initiate hydroxyurea treatment was 18.7 (±1.9 SD) versus a mean score of 15.8 (±3.0 SD) in those deciding not to initiate hydroxyurea. Reasons for not initiating treatment included fear of potential side effects, unsubstantiated doubts about the diagnosis, apprehension towards taking medication in general, and the absence of sickle cell disease-related symptoms in the patient.

Conclusion: Our study provides an example of a health literacy-based shared decision-making tool that can be applied to support the introduction of hydroxyurea treatment in children with sickle cell disease. Thereby supporting both caregivers and patients as well physicians in making an informed choice.

Topic: 003–Clinical and epidemiological studies

S. Babiker¹, A.O.D. Ofakunrin², S. Garg³, F.V. Ullam⁴, A. Oladejo⁵, E. Nwamu⁶, S. Ndoro¹, F. Nick¹, F. Afzal⁷, A. Sutcliffe⁷, B.P.D. Inusa⁸

Evelina London Guy's and St Thomas NHS Foundation Trust¹, Evelina London Guy's and St Thomas NHS Foundation Trust/Africa Research Innovative Initiative for Sickle Cell Education², University College London and Great Ormond Street Institute of Child Health London³, Crescent Kids⁴, Child and Adolescent Mental Health Services, South London and Maudsley NHS Foundation Trust⁵, Queen Elizabeth Hospital⁶, University College London and Great Ormond Street Institute of Child Health⁷, Kings College London⁸

Background: Pica is a disordered eating pattern marked by the persistent craving and consumption of non-nutritive substances for over a month, discordant with cultural practices, and occurring beyond normal childhood development. Symptoms vary depending on the ingested substances and can include poor weight gain, delayed development, iron deficiency, malnutrition, dental damage, gastrointestinal issues, and electrolyte imbalances. Pica also risks ingestion of toxic substances and pathogens. A notable but poorly understood link exists between pica and sickle cell disease (SCD), raising concerns particularly for children with SCD due to their already significant physical, mental, and social challenges. The aetiology of pica is unclear, but it is often associated with nutritional deficiencies and psychosocial factors, potentially serving as a coping mechanism for stress, anxiety, abuse or neglect. Understanding pica's behavioural dynamics is crucial for clinicians, psychologists, and parents to address the issue effectively.

Objectives: To determine the prevalence of pica and describe covariates such as age, sex, disease genotype, anaemia that may predict pica in children with SCD.

Methods: This cross-sectional study involved SCD children aged 3 to 18 years attending the paediatric haemoglobinopathy clinic at Evelina London Children's Hospital. Eligible patients were invited and given information leaflets and consent forms. A pre-tested anonymous questionnaire was used to collect data on socio-demographics and eating habits from each of the participants. Heights and weights were measured, and haematological parameters like haemoglobin concentration, serum ferritin, LDH, and reticulocytes were obtained from hospital records. Data were summarized using descriptive statistics.

Results: Of the 56 participants recruited, 30 (53.6%) were males, 42 (75.0%) were aged 5 to 14 years, and 44 (78.6%) had HbSS genotype. Twenty (35.7%) reported pica, with 55% being females and 55% aged 5–9 years. The mean age of children with pica was lower than those without pica (7.1 vs. 9.8 years) (Table 1). Ingested substances included paper, fabric, foam, wall paint chips, and sand (Figure 1). Complications reported by 15% of children with pica included constipation and abdominal pain. Only 25% of pica children had seen a psychologist, and only 50% of parents expressed concern about the pica behaviour. Compared to children without pica, those with pica had lower height (125.1 vs. 140.0 cm), weight (24.9 vs. 40.0 kg), and hemoglobin levels (88.9 vs. 98.3 g/L). Conversely, they had higher ferritin (159.7 vs. 107.0 µg/L), LDH (486.1 vs. 424.8), and reticulocyte counts (212.0 vs. 174.3).

Conclusion: This preliminary data show a high prevalence of pica among children with SCD. Pica poses a significant health risk for these children, necessitating vigilant monitoring and prompt intervention by healthcare workers and caregivers to prevent severe complications.

1. Lemanek et al. Clinical Pediatrics (Phila), 2002; 41(7), 493–500.

2. F Ahmed. Basic Research Journal of Medicine and Clinical Sciences, 2015; 4, 01–7.

3. Leung et al. Current Pediatric Reviews, 2019; 15, 164–169.

4. Ivascu et al. The Archives of Pediatrics & Adolescent Medicine, 2001; 155(11), 1243–1247.

5. Barker et al. British Dental Journal, 2005; 199, 271–273.

Topic: 003–Clinical and epidemiological studies

R.C. Raffaella Colombatti¹, J.J. John James², B.A. Biree Andemariam³, J.M. Johnny Mahlangu⁴, J.W. John Waller⁵, S.A. Samar Al-Behaisi⁵, G.M. Gareth Morrell⁶, C.T. Cassandra Trimnell⁷

University of Padova¹, Sickle Cell Society², University of Connecticut Health³, University of the Witwatersrand⁴, Novo Nord isk Health Care AG⁵, Madano⁶, Sickle Cell 101⁷

The LISTEN Survey was fully funded by Novo Nordisk. Novo Nordisk employees input into the survey design and content and are co-authors of this abstract.

Background: Clinical trial (CT) populations may under-represent some regions of the world where sickle cell disease (SCD) is prevalent, limiting the generalisability of findings. The Learnings and Insights into Sickle Cell Trial Experiences (LISTEN) Survey was a global survey that identified a need to communicate the potential benefits of CT participation for individuals and the wider SCD community, as well as the anticipated safety profile, to improve access and recruitment into CTs.¹

Aims: To explore potential geographic differences in the importance of factors affecting the ability and willingness of people with SCD (PwSCD) to participate in CTs, as identified in the LISTEN Survey.

Methods: From October 2022 to June 2023, PwSCD (≥18 years old) in 17 countries completed a quantitative survey assessing factors that affect the decision to participate in a CT across 5 categories. Respondents rated the importance of factors on a 7‑point scale (not at all to extremely important) or ranked them from most to least important. Responses are reported by region for Middle East and North Africa (MENA), Sub-Saharan Africa (SSA), South America (SA), North America (NA), Europe (EUR) and India (IN). Differences between the mean of each region and the mean of the other regions were assessed using two-proportion Z-tests.

Results: Overall, 1145 PwSCD (142 MENA, 307 SSA, 122 SA, 254 NA, 242 EUR, 78 IN) completed the survey; 58% were female and the median age was 30 years. The proportion of respondents not aware of CTs was large in IN (88%), MENA (39%) and SSA (39%), compared with 12% in SA, 5% in EUR and 5% in NA. Prior participation in an SCD CT was reported by 37% in NA, 33% in SA, 25% in EUR, 16% in SSA, 11% in MENA and 0% in IN. For questions about the potential impact of participation on daily life, responses were similar or had minor differences across regions. Regarding impact of receiving trial treatment, the potential to better manage symptoms was rated extremely/very important by a greater proportion of respondents in SA and by a smaller proportion in IN than in other regions (Figure 1A). Most respondents in SSA placed less importance on the potential for different side effects and the treatment not being as good as their current treatment than in other regions. When considering wider trial impact, more respondents in SA and fewer respondents in SSA and IN rated supporting new treatment developments for the benefit of other PwSCD extremely/very important than in other regions. Most respondents in SA rated increasing their knowledge about SCD as extremely/very important. Regarding CT information, understanding planned safety measures was most often ranked first or second in importance across regions, except in SA where how the trial treatment works, and in IN where who is leading the trial were ranked as one of the top two factors more than in the other regions (Figure 1B).

Summary/Conclusion: Awareness of and participation in CTs for SCD was low in IN, MENA, and SSA. Geographic differences in the importance of factors motivating or discouraging PwSCD to participate in CTs may reflect differences in education needs, local culture, or confidence in the healthcare system. These geographic differences should be considered when designing protocols to enhance recruitment and diversity in global CTs.

This abstract was accepted and presented at the EHA Annual Congress, 13–16 June 2024, Madrid, Spain; Abstract P1482

Topic: 003–Clinical and epidemiological studies

G. Reggiani¹, A. Fattorello Salimbeni², L. De Rosa², A. Volpato², F. Viaro², A. Pieroni², S. Mozzetta², F. Favruzzo², A. Pes ², M. Zaccagnino², M.P. Boaro¹, R. Manara³, R. Colombatti¹, C. Baracchini²

Pediatric Hematology Oncology Unit, Azienda Ospedale-Università Padova¹, Stroke Unit and Neurosonology Laboratory, Azienda Ospedale-Università Padova², Neuroradiology Unit, Azienda Ospedale-Università Padova³

Background: Cerebral vasculopathy is one of the complications of sickle cell disease (SCD) with more impact on survival, morbidity and quality of life. Most studies on children with SCD focus on the anterior brain circulation, not considering posterior circulation hemodynamics. In particular, the STOP trial evaluated exclusively distal internal carotid arteries and medium cerebral arteries to stratify patients according to their risk of stroke.

Aims: This study aimed to evaluate the parenchymal and vascular involvement of the posterior cerebral circulation and the role of transcranial ultrasound in detecting SCD children at a higher risk of developing ischemic lesions in that territory.

Methods: Posterior circulation involvement was evaluated by transcranial ultrasound and neuroimaging (MRI/MRA) in 92 children aged 2–18 affected by SCD (HbSS or HbSβ°), regularly monitored clinically over 18 years from March 1st 2005 to May 6th 2023. The following vessels were evaluated by Transcranial Color-Coded Doppler (TCCD) for each patient: right and left terminal internal carotid artery (TICA), middle cerebral artery (MCA), anterior cerebral artery (ACA), posterior cerebral artery (PCA) and top of the basilar artery (BA) via a transtemporal approach; vertebral arteries (VA) and BA via a transforaminal approach. Ultrasound findings were categorized according to the STOP trial protocol. The MRI/MRA protocol included 2D-FLAIR T2-weighted and 3D ToF sequences.

Results: Among the study population, 76.1% of patients were on treatment. The most frequently administered drug was Hydroxyurea (60.9%), while 15.2% had received chronic blood transfusions at the time of TCCD evaluation. The result of neurosonological evaluation was “Normal” in 48 patients (51.1%), while only one (1.1%) patient was categorized as “Abnormal”; 20 (21.7%) examinations were classified as “Inadequate”. Among 92 SCD children cerebral ischemic lesions were detected in 27 (29.3%). In particular, posterior circulation ischemic lesions were present in 17 (18.4%); this burden was not inferior to the one present in the anterior circulation [median volume 264 cc (IQR 66.0–753.5) versus 71.5 cc (IQR 38.5–665.5), p 0.44]. Posterior circulation stenoses were detected in 9 children (9.8%), always involving the posterior cerebral arteries (PCA). There was a significant association between vascular lesions in the posterior border zone and stenosis of the ipsilateral PCA (p < 0.0001). Values of time-averaged mean of the maximum velocity (TAMMV) in the posterior circulation vessels were higher in patients with ischemic lesions in that territory, while STOP criteria could not distinguish children with posterior cerebral infarcts from children without.

Summary/Conclusion: This study has shown a significant cerebral ischemic burden in the posterior border zones, with an increased rate of PCA stenosis and higher TAMMVs. Current STOP criteria do not seem to be an effective tool when applied to posterior brain circulation.

1. Adams et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. The New England Journal of Medicine, 1998; 339(1), 5–11.

2. Kwiatkowski et al. Post-STOP Study Group. Ischemic stroke in children and young adults with sickle cell disease in the postSTOP era. The American Journal of Hematology 2019; 94(12), 1335–1343.

3 Reggiani et al. Relationship between hemoglobin, hemolysis, and transcranial Doppler velocities in children with sickle cell disease: results from a long-term natural history study in Italy in the era of multimodal therapy. The European Journal of Haematology, 2023; 111(3), 414–422.

4. Bernaudin et al. Chronic and acute anemia and extracranial internal carotid stenosis are risk factors for silent cerebral infarcts in sickle cell anemia. Blood, 2015;125(10):1653–1661.

5. Ford et al. Silent infarcts in sickle cell disease occur in the border zone region and are associated with low cerebral blood flow. Blood, 2018; 132(16), 1714–1723.

6. Thangarajh et al. Magnetic resonance angiography-defined intracranial vasculopathy is associated with silent cerebral infarcts and glucose-6-phosphate dehydrogenase mutation in children with sickle cell anaemia. British Journal of Haematology, 2012; 159(3), 352–359.

7. Adegoke et al. Posterior circulation evaluation in patients with sickle cell anemia. Journal of Stroke & Cerebrovascular Diseases, 2016; 25(3), 717–721.

8. Peter et al. Transcranial Doppler ultrasound velocity, cerebral vasculopathy, and silent infarcts in sickle cell disease. Blood, 2010; 116 (21), 269.

9. Wang et al. Multicenter comparison of magnetic resonance imaging and transcranial Doppler ultrasonography in the evaluation of the central nervous system in children with sickle cell disease. Journal of the Pediatric Hematology Oncology, 2000; 22(4), 335–339.

Topic: 004–Infection, autoimmunity, nutritional deficiencies

M.A.I. Idris¹, L.R. Ruggieri², H.A.R. Rufai³, A.H. Hassan¹, I.N.I. Ibrahim¹, F.J.A. Abdullahi³, S.A. Awwalu¹, U.N. Nasiru¹, M.M. Muhammad⁴, S.A. Abdulkadir¹, F.B. Bonifazi², W.A. Atoyebi⁵

Department of Haematology & Blood Transfusion, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria,¹ Fondazione per la Ricerca Farmacologica Gianni Benzi Onlus, Bari, Italia,² Department of Paediatrics, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria,³ Antiretroviral Therapy Laboratory, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria,⁴ Oxford University Hospitals, NHS Trust, Oxford, UK⁵

Background: Sickle cell disease (SCD) patients have increased susceptibility to infections, especially bacterial pathogens. Infections are the most frequent complications in individuals with SCD. Hyposplenism as well as immune defects in SCD result in increased risks for infections with resultant morbidity and mortality. Encapsulated bacterial pathogens such as Streptococcus Pneumoniae,

Haemophilus influenzae type b (Hib) and pneumococcus are of special interests in SCD. This study was analysed during an African Research and Innovative initiative for Sickle cell Education (ARISE, EC GA No 824 021) secondment.

Aims: To determine the most prevalent infections among SCD patients reported at clinic visits at Ahmadu Bello University Teaching Hospital, Zaria, Nigeria from 1998 to 2023.

Methods: We reviewed records of SCD patients in our paediatric registry and extracted the patterns of infections reported at clinic visits using structural query searching.

Results: Data of 1961 SCD paediatric patients was retrieved from the registry. 1041 (53.1%) were male children, 906 (46.2%) female and 14 (0.7%) gender not recorded. There were 397 (50.3%) subjects with at least one infection and 392 (49.7%) with more than one infection. The most prevalent infections documented at clinic visits were Malaria 183 (9.3%), Osteomyelitis 132 (6.7%), acute diarrheal disease 45 (2.3%), acute respiratory infection 14 (0.7%), urinary tract infection 11 (0.6%) and pneumonia 7 (0.4%). Only 909 (46.4%) of the children had received routine immunization.

Conclusion: Infections are a significant presenting complication of SCD patients attending a tertiary clinic in northern Nigeria.

1. A Catherine Booth et al. Infection in sickle cell disease: A review. International Journal of Infectious Diseases, 2010.

2. B Brown et al. Prevalence and etiology of bacteremia in febrile children with sickle cell disease at a Nigeria tertiary hospital. Mediterranean Journal of Hematology and Infectious Diseases, 2017.

3. VP Dayana et al. Sickle cell disease, infection, penicillin, immunization. The Journal of Pediatrics, 2004.

Topic: 004–Infection, autoimmunity, nutritional deficiencies

T.A. Alshuaibi¹, W.A. Bajhmoum¹, A.M. Aljuhani¹, R.R. Alessawi¹

King Fahad Hospital Jeddah¹

Cholera is an acute diarrheal illness caused by toxigenic strains of the bacterium Vibrio cholerae (V. cholerae) serogroups O1 and O139. Although most cases are asymptomatic, symptomatic infections can result in copious watery diarrhea, leading to dehydration and even death if left untreated. Extraintestinal infections with V. cholerae, including bacteremia and meningitis, are rare but have been reported.^1–9 This report describes a highly unusual case of concurrent V. cholerae O1 meningitis and intracranial lesions in a 34-year-old male with sickle cell disease (SCD). The patient presented with a two-month history of persistent fever, watery diarrhea, and altered mental status. Cerebrospinal fluid (CSF) analysis yellow turbid fluid (Figure 1) with 5231 cells/µL (53.9% neutrophils and 43.4% monocytes), a protein level of 462 mg/dL, and glycorrhachia level of 26 mg/dL (serum glucose: 139 mg/dL). V. cholerae O1 was isolated from CSF and blood cultures. Despite appropriate antimicrobial therapy with ceftriaxone and doxycycline, the patient failed to improve. Brain MRI revealed bilateral ring-enhancing lesions in the basal ganglia (Figure 2). CSF testing was negative for Mycobacterium tuberculosis on smear, culture, and PCR. However, based on the neuroimaging findings, lack of response to antibiotics, and the patient's residence in a tuberculosis-endemic region, a presumptive diagnosis of CNS tuberculosis was made. Initiation of antituberculous therapy with isoniazid, rifampin, ethambutol, pyrazinamide, and adjunctive dexamethasone led to marked clinical and radiological improvement. The patient was discharged on a 12-month course of antituberculosis treatment, with oral dexamethasone tapered over four weeks. At follow-up, he remained asymptomatic with normal laboratory findings. This case highlights the increased susceptibility to unusual infections in patients with SCD and the importance of considering CNS tuberculosis in the differential diagnosis, even with negative CSF studies. Key aspects of management include prompt neuroimaging, appropriate antimicrobial therapy, and close monitoring of treatment response. The isolation of toxigenic V. cholerae O1 from CSF suggests enhanced virulence and invasiveness of this strain. In conclusion, clinicians should maintain a high index of suspicion for V. cholerae meningitis in SCD patients presenting with diarrhea and altered mental status. Rapid diagnosis, appropriate antibiotics, and consideration of alternative etiologies when patients fail to respond are crucial for optimal outcomes. Further research is needed to characterize the virulence factors and long-term sequelae of V. cholerae meningitis.

1. MZ Baig et al. Non O1, non O139 Vibrio cholerae bacteraemia in an infant; case report and literature review. The Journal of the Pakistan Medical Association, 2018; 68, 650–652. https://pubmed.ncbi.nlm.nih.gov/29808060/J

2. Y Hao et al. A case of non-O1/non-O139 Vibrio cholerae septicemia and meningitis in a neonate. The International Journal of Infectious Diseases, 2015; 35, 117–119.

3. EC Bustos et al. Vibrio cholerae O1 meningitis in an immunosuppressed child. The Pediatric Infectious Disease Journal, 1996; 15, 722–723.

4. LG Rubin et al. Vibrio cholerae meningitis in a neonate. The Journal of Pediatrics, 1981; 98, 940–942.

5. LS Naidu et al. Vibrio cholerae non-0:1 meningitis in an infant. The Pediatric Infectious Disease Journal, 1993; 12, 879–881.

6. EA Ismail et al. A case of non-O:1 Vibrio cholerae septicemia with meningitis, cerebral abscess and unilateral hydrocephalus in a preterm baby. European Journal of Clinical Microbiology & Infectious Diseases, 2001; 20, 598–600.

7. EL Fearrington et al. Letter: non-cholera vibrio septicemia and meningoencephalitis. Annals of Internal Medicine, 1974; 81, 401.

8. HL Chan et al. Cutaneous manifestations of non-01 Vibrio cholerae septicemia with gastroenteritis and meningitis. Journal of the American Academy of Dermatology, 1994; 30, 626–628.

9. C Suankratay et al. Non-serogroup O:1 Vibrio cholerae bacteremia and cerebritis. Clinical Infectious Diseases, 2001; 32, 0–9.

Topic: 004–Infection, autoimmunity, nutritional deficiencies

A.I.L. Ladu¹, A.M. Abba², F.M. Abulfathi², C. Jeffery³, I. Bates³

Department of hematology and Blood Transfusion¹, University of Maiduguri², Liverpool School of Tropical Medicine³

Background:

Table 1: Association of clinical and laboratory parameters with hepatitis B surface antigen (HBsAg).

Sickle cell disease (SCD) is an inheritable condition characterised by chronic haemolytic anaemia. Affected individuals often require repeated blood transfusion thereby placing them at risk of transfusion-transmitted infections such as hepatitis B virus (HBV).^1,2 Hepatitis B virus (HBV) infection is a hepatotropic virus capable of causing chronic liver disease including cirrhosis and cancer; it is a major cause of morbidity and mortality in Sub-Saharan Africa where the majority of individuals with SCD reside.^3,4 The current study sought to determine the seroprevalence of Hepatitis B surface antigen (HBsAg), a marker of acute HBV infection, among SCD patients and the association with some selected risk factors.

Methods: This cross-sectional hospital-based study was conducted at the University of Maiduguri Teaching Hospital, North-Eastern Nigeria from November 2020 to September 2021. Patients' information was obtained using a structured questionnaire. Venous blood was obtained for complete blood count, reticulocyte percentage, and liver enzymes. Patients were screened for HBsAg using an enzyme‑linked immunosorbent assay test. Abdominal ultrasound was used to assess liver size and echotexture.

Results: A total of 354 SCD patients consisting of 214 steady-state patients and 140 acutely ill patients were included in the study. Hepatitis B surface antigen (HBsAg) was available for 297 patients (83.9%). Eight patients were HBsAg positive giving a prevalence of 2.7%. Of note, the prevalence was higher among the steady state patients [n = 7/8 (87.5%)] than the acutely ill patients (Table 1). Five out of the eight patients with positive HBsAg results had previous history of blood transfusion whereas the remaining three patients had never been transfused. None of the under-five children were seropositive for the virus. Levels of bilirubin (total and direct) and reticulocyte percentage appeared high, and the liver size appeared low among patients with positive HBsAg results, however, this was not statistically significant. None of the SCD patients had an abnormal liver echotexture on an ultrasound scan.

Conclusion: Although the overall prevalence of HBsAg was low in this study, the high occurrence among asymptomatic patients calls for close screening of patients and identification of individuals who may benefit from early intervention before the development of chronic sequelae from infection with the virus. Also, consideration of other potential sources of infection other than blood transfusion among the patients should be given further consideration during risk assessment.

1. OO Akinyanju. Profile of sickle cell disease in Nigeria. Annals of the New York Academy of Sciences, 1989; 565, 126–136.

2. AS Wayne et al. Transfusion management of sickle cell disease. Blood, 1993; 81(5), 1109–1123.

3. M Chamberland et al. Emerging infectious disease in blood safety. Emerging Infectious Diseases, 2001; 7, 552–553.

4. BJ Bojuwoye. The burden of Viral Hepatitis in Africa. The West African Journal of Medicine, 1997; 16(4), 198–203.

Topic: 005–Ageing and end organ damage

I.C. Hawley¹, M. Lee², C.A. Clark¹, K. Shmueli², F.J. Kirkham³

UCL GOSH Institute of Child Heal¹, UCL Department of Medical Physics², UCL GOSH Institute of Child Health³

Introduction: Chronic hypoxia is hypothesised to be the cause of the long-term cognitive impairment seen in children with Sickle cell anaemia (SCA) with or without stroke. The complex mechanisms of injury display evidence of interdependence but are yet to be fully understood. Chronic hypoxia and subsequent tissue injury are thought to be caused by the inability of the cerebrovascular dilatory reserve (CVR) to maintain stable oxygen delivery to the tissue. Compensatory mechanisms include alteration of Oxygen extraction fraction (OEF), the proportion of oxygen taken up by the tissue compared to the overall oxygen supplied to the tissue. A change in OEF should therefore give evidence of progressive haemodynamic burden and subsequent cognitive decline. MRI estimation of OEF is a potential noninvasive measure of haemodynamic compromise in SCA.

Methods: QQ is a method of measuring cerebral OEF developed by Cho et al.¹⁻⁴ It is a combination of two MRI techniques, quantitative susceptibility mapping (QSM) and quantitative BOLD. In this work, a version of the QQ algorithm, QQ-CCTV (temporal clustering, tissue composition, and total variation) was used to estimate the cerebral OEF in a cohort of children with SCA and healthy paediatric controls recruited after informed consent. The standard algorithm as well as a haematocrit (HCT) corrected version of QQ-CCTV were evaluated. SCA patients had HCT concentrations measured as close to the MR imaging as possible, controls were not bled for ethical reasons.

Results: In 58 patients with SCA (age 8.0–19.6; median 13.7 years; 31 male) the OEF using the standard QQ-CCTV method was reduced in the grey matter and white matter compared to 17 healthy controls (age 8.4–17.1; median 13.7; 7 male). No difference was seen in the cerebrospinal fluid.

Using the HCT-corrected QQ-CCTV, 56 patients with SCA (age 8.02−18.00 years; median 13.7; 32 male) the OEF was higher in all brain regions compared to the 17 healthy controls and the standard QQ-CCTV method.

Summary/Conclusion: An increase in cerebral OEF was found in patients with SCA using a haematocrit-corrected version of the QQ-CCTV, suggesting that the amount of oxygen taken up by the tissue was higher than in the healthy controls. Limitations include the lack of HCT measurement in the controls. Further research will include comparison of OEF with cerebral blood flow measured with arterial spin labelling and investigation of any association with vasculopathy and cerebral infarction.

Figure 1: Output images of OEF (%) venous blood volume fraction (ν) for a subject under the age of 18 with SCD from, Top: QQ-CCTV algorithm with standard assumed venous HCT concentration of 47.0%.⁵ Bottom: QQ-CCTV algorithm with HCT correction, HCT concentration = 20.6%.

Table 1: The average percentage OEF values within different brain regions for patients versus healthy controls estimated via the use of QQ-CCTV and haematocrit-corrected QQ-CCTV.

1. J Cho et al. Magnetic Resonance in Medicine, 2021; 86, 2635–2646.

2. J Cho et al. Magnetic Resonance in Medicine, 2018; 80, 1595–1604.

3. J Cho et al. Magnetic Resonance in Medicine, 2020; 83, 844–857.

4. Z Liu et al. Magnetic Resonance in Medicine, 2018; 79, 2795–2803.

5. Sakai et al. Journal of Cerebral Blood Flow & Metabolism, 1985, 207–213.

Topic: 006–Health services and outcomes research including psychology

S.H. Hamdule¹, F.J.K. Kirkham¹

UCL Great Ormond Street Institute of Child Health¹

Background: Sickle cell anaemia (SCA) is an inherited disorder characterised by abnormal haemoglobin production, resulting in rigid, sticky, sickle-shaped red blood cells. These cells often undergo intravascular haemolysis, leading to complications such as stroke and silent cerebral infarcts.¹ Cerebral ischaemic events in SCA are associated with impaired cerebral haemodynamic mechanisms particularly affecting cerebral blood flow (CBF) due to blood vessel occlusion or stenosis, endothelial damage,² and exhaustion of cerebrovascular reserve,^3,4 even in those with normal MRI and TCD.^4,5 Studies use techniques like PET and CT,^6–9 and non-invasive methods such as ASL-MRI and DSC-MRI to measure CBF.^10,11 However, variability in measurements exists due to technical differences in CBF estimation.^12,13 Similarly, recent neuroimaging investigations have included other dynamic markers of cerebral haemodynamic compromise including oxygen extraction fraction (OEF),^14,15 cerebral metabolic rate (CMRO₂), cerebrovascular reserve (CVR), and oxygen saturation (rSO₂).^16–21 A comprehensive review of neuroimaging techniques as well as various parameters of cerebral haemodynamic mechanisms is needed to guide research as well as clinical practice. Hence, this systematic review was undertaken and included all neuroimaging studies on CBF, OEF, CVR, and rSO₂ in individuals with SCA. This review also included a meta-analysis of CBF and OEF studies.

Methods: We searched six databases (Embase, Medline, Scopus, Web of Science, PubMed, and PsycINFO) for terms like “cerebral haemodynamic” and “cerebral blood flow” paired with “sickle,” “neuroimaging,” and “cognition.” Eligible articles measured CBF, OEF, cerebral oxygen saturation, and cerebrovascular reserve using appropriate neuroimaging modalities. The Critical Appraisal Skills Programme (CASP) case-control checklist assessed the quality of cross-sectional studies. Studies comparing CBF and OEF between individuals with SCA and controls were included in the meta-analysis, with a random-effect model used to estimate the standardized mean difference.

Results: The database search yielded 943 references, with 69 studies included in the review: 27 reported CBF, 21 reported both CBF and OEF, 9 reported cerebrovascular reserve, and 8 reported oxygen saturation. Most studies were conducted in the USA and the UK. CBF values were higher in individuals with SCA compared to controls, as confirmed by the meta-analysis [SMD = 1.5006 (CI: 1.2218; 1.7793); p < 0.0001]. OEF studies showed mixed results, rendering the meta-analysis inconclusive [SMD = −0.32 (CI: −1.25; 0.60); p = 0.45]. Subgroup analysis of CBF based on ROI suggests increased blood flow to the grey matter compared to WM regions. Subgroup analysis based on methods of investigation (T-2 TRIR and TRUST) for OEF show variations in methodology causing differences in OEF estimation. Studies reporting both CBF and OEF indicated reduced CMRO2 and capillary transit times. CVR studies, using various MR techniques, consistently reported reduced CVR due to poor cerebral auto-regulation. Oxygen saturation (rSO₂) was lower in individuals with SCA compared to healthy controls.

Conclusion: Higher CBF in individuals with SCA compensates for increased cerebral oxygen demands. Sub-group analysis indicates that grey matter CBF is prioritised, leaving white matter CBF vulnerable to hypoxic damage, potentially linked to white matter hyperintensities.²² Dysregulated capillary transit times and reduced cerebrovascular reserve further compromise cerebral autoregulation, potentially elevating blood pressure in young SCA patients.^23,24 The systematic review and meta-analysis highlight cerebral hemodynamic compromise in SCA, suggesting the need for refined non-invasive imaging methods and personalised treatment strategies. Further research is recommended to optimize clinical management and improve outcomes for individuals with SCA.

Clinical Implications: The review highlights the need for regular monitoring of cerebral haemodynamic mechanisms in SCA patients. Elevated CBF and reduced cerebrovascular reserve indicate a risk for cerebrovascular complications, emphasising the use of advanced non-invasive imaging techniques like ASL-MRI in routine assessments. Early detection of cerebral issues and timely interventions can be achieved through these methods. Personalised treatments, including tailored hydroxyurea therapy and transfusion protocols, and managing blood pressure in young SCA patients are essential to mitigate risks. A comprehensive, multidisciplinary approach is crucial for improving outcomes in SCA patients.

Topic: 006–Health services and outcomes research including psychology

L.M.B. Carlos¹, D.M. Brunetta¹, N.C.M. Castro¹, F.L.N. Benevides¹, S.A.T. Barbosa¹, T.O. Reboucas¹, M.F. Nobre¹, A.M.V. Silva¹, C.M.L. Monteiro¹, A.K.S. Lucas¹, F.J.C. Santos¹, M.I.A. Oliveira¹, N.M. Beserra¹, L.E.M. Carvalho¹

HEMOCE¹

Background: Sickle cell disease (SCD) is a chronic and progressive inherited blood disorder caused by a single mutation in the hemoglobin β-chain, resulting in abnormal hemoglobin S (HbS). According to the World Health Organization, this often-overlooked genetic disease is a life-threatening condition affecting millions of people worldwide. The overall treatment goals in SCD are to relieve pain, prevent complications, and decrease mortality, utilizing treatments such as hydroxyurea, antibiotics, analgesics, vaccinations, iron chelators, and blood transfusions. Chronic transfusion is an effective option for treating or preventing multisystem complications of SCD.

Aims: This study aims to describe our center's experience with the implementation of automated red blood cell exchange (aRBCX) as a modified treatment modality for SCD patients in a chronic transfusion program.

Methods: The implementation of aRBCX at our center began in 2021, involving operational logistics improvements such as staff and equipment training, benchmarking, protocol definition, and initial patient selection. Eligible patients with SCD, including those with previous strokes, recurrent vaso-occlusive crises, and pregnant patients with a previous complicated pregnancy or those with complications in the current pregnancy, were included in the regular aRBCX program.

Results: From 2021 to the present, 18 patients have been enrolled in our aRBCX program. A total of 74 procedures have been performed, with 529 red blood cell units transfused. Only one patient presented alloimmunization (anti-D in a RhD-positive patient). There were no hemolytic transfusion reactions recorded. One patient presented a severe vasovagal episode, but after reducing the exchange volemia, the procedures occured without any new events. All sessions were conducted while maintaining isovolemic status and using peripheral access. The target HbS concentration was individualized based on each patient's condition. Our data show that aRBCX effectively reduced HbS levels, required fewer clinic visits, and improved patients' quality of life. This approach also addressed challenges such as venous access, the number of pRBCs transfused, and adverse reactions.

Conclusions: Our successful automated transfusion program can serve as a model for national implementation, resulting from improvements in local public health system infrastructure. Enhancing preventive care and clinical patient management are crucial factors in reducing the morbidity and mortality associated with sickle cell disease.

1. FB Piel et al. The Lancet Haematology, 2023; 10, 8.

2. S Kelly. Hematology American Society Hematology Education Program, 2023; 2023, 1.

Topic: 006–Health services and outcomes research including psychology

M.A.A. Ampomah¹, A.A. Anum², K.H.A. Amegan-Aho¹, A.H. Hood³, F.J.K. Kirkham⁴

University of Health and Allied Sciences, Ho, Volta Region Ghana¹, University of Ghana, Legon², University of Manchester, United Kingdom³, University College London, UK⁴

Background: Sickle cell disease (SCD) is recognized as the most prevalent hereditary hemoglobinopathy with significant public health impact.¹ Due to early detection through newborn screening, advancement in medicine and psychosocial care, and patient education, people with SCD are now living longer into adulthood.^2,3 However, in low- and middle-income countries, the absence of welfare, disability, and unemployment benefits forces many adult SCD patients to work for their survival even in the face of severe health challenges.⁴ While employment generally improves the financial stability of individuals, its effect on the Quality of Life (QoL) of adult SCD patients is poorly understood. Most of the QoL literature has focused on children,^5,6 and the few adult studies have employed non-disease-specific QoL.^7,8

Objective: This cross-sectional study was to investigate the predictors of QoL in adults living with SCD.

Methods: One hundred and twenty adult SCD patients aged 18–56 were administered the Sickle Cell Illness Impact Measurement Scale (SIMS) to assess five main domains of QoL: general health perception, physical functioning, social functioning, emotional well-being, and quality of care.⁹ First, a Univariate Linear Regression test was conducted to determine socio-demographic and clinical factors associated with the overall QoL outcomes and QoL domains. The significant predictors were simultaneously included as independent variables in a multivariate linear regression model to assess their ability to predict the QoL outcome and the specific QoL domains.

Results: In general, adult patients with SCD had a poor overall quality of life (QoL) [Mean (Standard Deviation) = 468.96 (56.05)]. Employment was a risk factor for overall quality of life in these patients [B = −22.48 (95% CI: −44.09, −0.88) p = 0.042]. General health perception was negatively influenced by employment [B = −4.58 (95% CI: −7.68, −1.47) p = 0.004] and frequency of crisis [B = −5.04 (95% CI: −8.06, −2.02) p = 0.001], but positively influenced by the use of Hydroxyurea medication [B = 6.55 (95% CI: 2.53, 10.56) p = 0.002]. Physical functioning declined with increasing age [B = −0.20 (95% CI: −0.40, −0.01) p = 0.043]. Emotional functioning was positively predicted by the age at SCD diagnosis [B = 0.84 (95% CI: 0.07, 1.60) p = 0.003]. Both age at SCD diagnosis [B = 0.25 (95% CI: 0.09, 0.40) p = 0.003] and Hydroxyurea medication use [B = 6.01 (95% CI: 1.24, 10.79) p = 0.014] were positive predictors of social functioning. Quality of care at the clinic was negatively impacted by employment [B = −6.15 (95% CI: −11.49, −0.80) p = 0.025] and age at SCD diagnosis [B = −0.33 (95% CI: −0.58, −0.09) p = 0.008], but positively influenced by participation in an SCD support group [B = 2.10 (95% CI: 0.16, 4.04) p = 0.034].

Conclusion: These findings have significant clinical and policy implications. Integrating targeted interventions into the clinical and psychosocial care of SCD patients, particularly employed adult patients, could help reduce complications and enhance quality of life. Furthermore, developing and implementing SCD policy aimed at recognizing SCD as a disability and allowing patients to benefit from social protection schemes, such as Livelihood Empowerment Against Poverty (LEAP) and disability support, should be considered in Ghana. This would help alleviate the financial burden and stress for those with severe forms of SCD who are unable to work. The SCD policy should also advocate for Worker's Individual Support Plans (WISP) to ensure non-discriminatory and supportive workplace environments, enabling adult SCD patients to thrive.

1. ME Swanson et al. Disability among individuals with sickle cell disease. AMEPRE, 2011; 41(6), S390–S397. https://doi.org/10.1016/j.amepre.2011.09.006

2. L Hsu et al. White paper: pathways to progress in newborn screening for sickle cell disease in sub-Saharan Africa. Journal of Tropical Diseases & Public Health, 2018; 6(2).

3. SK Ballas. Sickle cell disease: classification of clinical complications and approaches to preventive and therapeutic management. Clinical Hemorheology and Microcirculation, 2018; 68(2–3), 105–128. https://doi.org/10.3233/CH-189002

4. LM Banks et al. Disability and social protection programmes in low-and middle-income countries: a systematic review. Oxford Development Studies, 2017; 45(3), 223–239.

5. AM Hood et al. Biopsychosocial predictors of quality of life in paediatric patients with sickle cell disease. Frontiers in Psychology, 2021; 12, 681137.

6. M Stokoe et al. Health related quality of life in children with sickle cell disease: a systematic review and meta-analysis. Blood Reviews, 2022; 56, 100982.

7. D Bulgin et al. Stigma and quality of life in adults with sickle cell disease in Jamaica and the United States. Psychology, Health & Medicine, 2023; 28(5).

8. KS Esham et al. Assessment of health-related quality of life among adults hospitalized with sickle cell disease vaso-occlusive crisis. Blood Advances, 2020; 4(1), 19–27.

9. P Adams-Graves. Development and validation of SIMS: an instrument for measuring quality of life of adults with sickle cell disease. American Journal of Hematology, 2008; 83(7), 558–562. https://doi.org/10.1002/ajh.21146

Topic: 006–Health services and outcomes research including psychology

A. Haimed¹, R. Weiss², S. Kwon², R. Bhat³, S. Badawy³

Division of Hematology, Oncology and Stem Cell Transplantation, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago,¹ Department of Pediatrics, Northwestern University Feinberg School of Medicine², Divison of Hematology, Oncology and Stem Cell Transplantation, Ann and Robert H. Lurie Children's Hospital of Chicago³

Background: Vaso-occlusive event (VOE) is the most common reason for hospitalization in pediatric patients with sickle cell disease (SCD). While intravenous (IV) fluid therapy in patients with VOE can help reduce red blood cell sickling, clinical practices vary across providers and institutions, in part due to a lack of evidence on the optimal IV fluid regimen. Excessive IV fluid therapy in hospitalized patients can lead to volume overload and resultant complications. In this retrospective analysis, we examined the relationship between IV fluid rate and hospital length of stay (LOS). We assessed the relationship between IV fluid rate and risk for adverse events, such as acute chest syndrome (ACS), pediatric intensive care unit (ICU) transfer, and readmission within 4 weeks.

Aims: Primary Aim: Investigate the relationship between IV fluid therapy and hospital length of stay (HLOS) in pediatric patients with sickle cell disease admitted with VOE.

Secondary Aim: Evaluate the incidence of adverse events associated with IV fluid therapy. Adverse events defined as the development of acute chest syndrome (ACS) during admission, transfer to the pediatric intensive care unit, and re-admission within 28 days from previous admission.

Methods: This was a retrospective analysis from a single center between January 2015 and April 2020. Patients with SCD (HbSS, HbSC, HbS-β0 thalassemia, or HbS-β⁺ thalassemia), age 0–30, with consecutive admissions hospitalized for VOE were included after local IRB approval. Records were reviewed for demographic variables and clinical parameters such as IV fluids administered, medical history, pain medication use, and hospitalization outcomes. For the first 3 days of each admission, an “IV fluid ratio” was calculated by dividing actual IV fluid rate administered by estimated weight-based maintenance IV fluid (mIVF) rate. A multivariate linear regression analysis of average IV fluid ratio and LOS was performed.

Results: In this study, 617 hospital admissions in 162 patients were included. ACS occurred in 141 admissions (22.9%), 55 (9%) of which developed during the admission. ICU transfer occurred in 15 (2.4%) admissions (7 for exchange transfusion, 7 for respiratory failure, 1 for hypertension). Readmission within 4 weeks occurred in 121 (19.7%) admissions. One hundred twenty-one (19.7%) of the 617 hospitalizations required readmission within four weeks of their previous admission.

Our analysis showed a positive association between LOS and IV fluid ratio. For each additional 0.5 times the mIVF rate, the LOS increased by 0.53 days (p < 0.001; CI: 0.609–0.989). Multivariate logistic regression analysis showed that IV fluid therapy did not increase the odds of ACS, ICU transfer or readmission within 30 days.

Summary/Conclusion: We found that increased IV fluid therapy was associated with prolonged LOS, which places a burden on patients, families, and the health system. There was no association with adverse events during hospitalization. Further investigation is needed to determine the optimal IV fluid regimen to manage VOE, decrease complications, and reduce resource utilization.

1. Rees et al. British Journal of Haematology, 2003; 120(5), 744–752.

2. Okomo et al. Cochrane Database of Systematic Reviews, 2017; 7(7), CD005406.

3. Gaut et al. Annals of Hematology, 2020; 99(6), 1217–1223.

4. Gaartman et al. British Journal of Haematology, 2021; 194(5), 899–907.

5. Panepinto et al. Pediatric Blood & Cancer, 2005; 44(2), 182–186.

Topic: 006–Health services and outcomes research including psychology

S.C.C. Chatzimatthaiou¹, F.B. Bonifazi², R.F. Colombatti³, F.C. Cremonesi⁴, A.G. Glenthoej⁵, J.T.S. Synodinos⁶, A.C.G. Gimbert⁷, C.S.C. Stephanou¹, D.A. Antic⁸, B.D. Durmaz⁹, E.G. Gavriilaki¹⁰, B.I. Inusa¹¹, A.L. Landi², M.P. Pellegrini¹², M.M.P. Pereira⁷, P.K.C. Kountouris¹

Cyprus Institute of Neurology and Genetics¹, Fondazione per la Ricerca Farmacologica Gianni Benzi Onlus², University of Padova³, INRIA⁴, Copenhagen University Hospital⁵, National and Kapodistrian University of Athens⁶, Vall d'Hebrón Institut de Recerca⁷, University Clinical Center Serbia⁸, Ege University⁹, Papanicolaou Hospital¹⁰, King's College London¹¹, Assistance Publique Hopitaux De Paris¹²

Haemoglobinopathies are the commonest monogenic disorders with variable clinical manifestations. While they were once prevalent primarily in the malaria-endemic regions, haemoglobinopathies have spread globally, largely due to the increase in global migration. This widespread prevalence imposes a substantial economic and quality-of-life burden on affected individuals. However, in numerous countries, the true prevalence of haemoglobinopathies remains underestimated due to the absence of national registries, limited patient access to diagnosis and treatment, and a lack of international collaboration.

To bridge this gap, in 2023, the COST Action CA 22 119 “Haemoglobinopathies European Liaison of Medicine and Science” (HELIOS), a global network of experts in haemoglobinopathies, was formed. HELIOS aims to enhance patient care and the quality of life of individuals affected by these conditions by fostering collaboration to ultimately harmonise clinical and laboratory practices and management on a global scale. The network consists of experts from a vast variety of fields including clinical research, laboratory genetics and molecular diagnosis, computational biology, bioethics, data management, and sectors such as universities, research centres, healthcare centres, biobanks, patient liaison agencies, and the private sector.

HELIOS is structured into five distinct working groups, covering a spectrum from clinical and laboratory aspects to data management. Over the next four years, based on the efforts of these working groups, the network aims to comprehensively map diagnostic centres, review current practices, and map data availability across Europe and beyond. Subsequently, leveraging the expertise of the participants, a set of clinical and diagnostic guidelines will be published to harmonise disease management collectively and thereby optimise patient care. Moreover, by mapping the current availability of data among network participants, the network aims to stimulate innovative ideas and cultivate fresh collaborations to advance the development of novel therapies.

Finally, HELIOS hopes to cultivate a promising future by providing young researchers and innovators (YRIs) the unique opportunity to work closely with more experienced experts within the field through mentoring and exchange programmes. HELIOS extends grant support to YRIs for travelling to institutions across the world, enabling them to acquire knowledge, master new techniques, or refine their skills. Moreover, funding is also allocated for online mentorship to sustain collaborations or overcome travel challenges.

In conclusion, the formation of the HELIOS COST Action CA 22 119 marks a significant step forward in addressing the challenges posed by haemoglobinopathies on a global scale. By bringing together a diverse network of experts from various fields and sectors, HELIOS aims to harmonise clinical and laboratory practices, optimise disease management, and improve patient care and quality of life. Over the next four years, HELIOS will work diligently to map diagnostic centres, review current practices, and enhance data availability, all with the ultimate goal of fostering innovation and collaboration to advance the development of novel therapies.

Furthermore, by providing support and opportunities for young researchers and innovators through mentoring and exchange programmes, HELIOS are investing in the future of haemoglobinopathy research, ensuring that the fight against these disorders continues.

Topic: 006–Health services and outcomes research including psychology

G. Queiroz¹, T. Novais², K. Pimenta³, C. Lobo⁴, L. Andrade⁵, B. Santos⁶, C. Coelho⁷, F. Amad⁸, D. Carvalho⁹, P. Kjöllerström¹⁰, C. Bento¹, J. Hankins³

Universidade de Coimbra¹, Ministério da Saúde do Brasil², St Jude Children's Research Hospital³, Hemorio⁴, Hospital Universitário Agostinho Neto⁵, Hospital Pediátrico David Bernardino⁶, Centro Pediátrico Renato Grandi⁷, Hospital Central de Maputo⁸, Hospital Dr. Ayres de Menezes⁹, Hospital de Dona Estefânia - ULS de São José¹⁰

Background: Sickle cell disease (SCD) stands as Africa's most prevalent genetic disease, comprising a significant global burden and high under-5 mortality.¹ Despite this, it remains a neglected condition.² With a combined SCD population of approximately one million, this reality is even more acute in Portuguese-speaking countries, where language barriers foster isolation and institutional neglect. However, the hardship affecting SCD outcomes across Portuguese countries remains poorly characterised.

Aims: The primary objective is to obtain a comprehensive overview of the barriers and facilitators to SCD care delivery across Portuguese speaking countries. The study aims to identify existing policies and practices while highlighting areas where support is lacking. Ultimately, the goal is to foster national policies and improve capacity-building and research planning for SCD in the Lusophone community.

Methods: We employed a qualitative approach, utilising a structured online questionnaire distributed to healthcare professionals engaged with SCD care or research in Lusophone countries: Angola (AO), Brazil (BR), Cape Verde (CV), Guinea-Bissau (GW), Mozambique (MZ), Portugal (PT), and São Tomé and Príncipe (ST). The questionnaire had 92 items encompassing 10 domains. Healthcare institutions were selected through a snowball sampling technique, commencing with members of the recently formed ALUA - Alliance of Lusophone Specialists on Sickle Cell Disease. A descriptive analysis provides a comprehensive snapshot of each country's capacity, barriers, and resources for SCD care.

Results:

Institutions: We received 29 answers from seven Lusophone countries, spanning 22 public and one private institution, with a median of four participants per country. The total number of patients with SCD per institution ranged from 100 to >500, depending on the country's size. Most were under the age of 10 years. All of them estimated losing approximately one-quarter of patients' follow-up during the pediatric-to-adult care transition. Though only two-thirds could assess mortality data, most institutions reported a mean age of death >30 years old, but three Angolan institutions had mean ages of death under age 5.

Screening programmes: Only BR and PT had universal newborn screening programmes for SCD. AO reported a regional screening programme. Premarital or pregnancy screening was reported in BR, and PT, but only at regional or subpopulational levels.

Healthcare system capacity: There was a great disparity across countries. Importantly, hydroxyurea was not available in GW at all.

Packed Red blood cell transfusions were available in most countries but with severe safety constraints and were scarce in GW and ST.

Imaging studies, including magnetic resonance imaging and transcranial Doppler, were scarce to unavailable in all, but AO, BR, CV and PT institutions. There were no haematologists in GW and ST. There, patients with SCD are followed by general practitioners (GP) and paediatricians. In the remaining institutions, patients are cared for mainly by haematologists and paediatricians, with some GP involvement.

Summary/Conclusions: Our study found significant variation in SCD care capacity across Lusophone countries. African countries had the largest gaps in diagnostics and therapeutics, while Brazil and Portugal lacked care practice guidelines, workforce capacity, and better-quality data. This information will hopefully inform the development of priorities and initiatives in Lusophone countries and facilitate discussions with health ministries and funders.

1. Thomson et al. Lancet Haematology, 2023; 10, 8.

2. Osei et al. Lancet Haematology, 2023; 10, 8.

Topic: 006–Health services and outcomes research including psychology

Linda Paul Athman¹, Fatima Mussa², Honesta John Kipasika², Agnes Jonathan¹, Emmanuel Balandya¹, Julie Makani¹

SPARCO Tanzania¹, Muhimbili University of Health and Allied Sciences²

Background: Depression commonly arises among adolescents who have experienced long-standing psychosocial difficulties including chronic illnesses. Globally, 1 in every 7 (14%) adolescents experience mental health conditions. Tanzania is among the top 5 countries in Sub-Saharan with the highest prevalence of sickle cell anemia estimated at 8000–11,000 births per year. With improved care and advanced treatment modalities, children are surviving into adolescence and adulthood being faced with psychosocial and mental health burden.

Aim: This study aims to assess the magnitude of depression, associated factors, and lived experiences among adolescents with SCA.

Methodology: A sequential dominance mixed method research study was conducted on adolescents aged 11–19 years who attended sickle cell clinics from October 2023 to March 2024. Sociodemographic and clinical profile data were collected using structured questionnaires. A validated Patient Health Questionnaire (PHQ-9) tool was used to screen for depression. Experiences of adolescents with depression were obtained through in-depth interviews. Univariate and multivariable analysis were used for the associated factors. A p < 0.05 was considered statistically significant. Qualitative data was analyzed using NVivo 11 pro; codes, themes and subthemes were derived and final write-up was made.

Results: Among 326 adolescents enrolled, 216 (54%) had depression; of which, 167 (38.7%) mild, 48 (14.7%), moderate, and 1 (0.3%) severe depression. 15% of adolescents with SCA had clinical depression (moderate to severe depression). Painful episodes were significantly associated with depression (aOR 2.49) (95% CI: 1.17−5.29, p = 0.01). Majority of adolescents experienced loneliness and isolation and had not fully accepted the reality of living with SCA. Adaptive and maladaptive behaviors were observed as the coping mechanisms when depressed. Social challenges experienced included bullying, name-calling, and fears of betrayal. Their main sources of support were parents, friends, and teachers.

Conclusion: Depression is common among adolescents with SCA in our setting. Painful episodes experienced by these adolescents were significantly associated with depression. Depressed adolescents commonly experienced feelings of loneliness and isolation. Social support, coping mechanisms, and acceptance play pivotal roles in their well-being. Understanding these experiences can inform targeted interventions and support systems for this vulnerable population.

Recommendations: This study highlights the need for screening adolescents with SCA for depression and integration of mental health services in sickle cell clinics. Prevention and adequate management of frequent painful is crucial for these adolescents. Targeted interventions should focus on good coping strategies, acceptance and strengthening social support systems.

Topic: 006–Health services and outcomes research including psychology

F. Bernaudin¹, A. Al Zayed², K.A. Anie³, M.E. Fields⁴, E.S. Klings⁵, C. Lobo⁶, O. Mboma⁷, S. Saraf⁸, P. Connes⁹, C. Makowski¹⁰, R. Kesse-Adu¹¹, E. Riehm Meier¹², R. Wirz¹³, W. Smith¹⁴

Centre Hospitalier Intercommunal Créteil¹, Inherited Blood Disorders, Qatif Central Hospital, Qatif Health Network², Imperial College London; Brent Sickle Cell and Thalassaemia Centre, London North West University Healthcare NHS Trust³, Division of Hematology and Oncology, Department of Pediatrics, Washington University School of Medicine⁴, The Pulmonary Center, Boston University Chobanian & Avedisian School of Medicine⁵, Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti, SES/RJ⁶, Helios Universi tätsklinikum Wuppertal⁷, Comprehensive Sickle Cell Center, Section of Hematology–Oncology, University of Illinois Hospital⁸, Laboratory LIBM, Vascular Biology and Red Blood Cell Team, Université de Lyon⁹, Internal Medicine Department, Centre Hospitalier Universitaire Grenoble Alpes¹⁰, Guy's and St. Thomas' NHS Foundation Trust¹¹, Pfizer Inc¹², Pfizer AG¹³, Division of General Internal Medicine, Department of Medicine, Virginia Commonwealth University, Medical College of Virginia¹⁴

Background: Remittive therapies for SCD have increased over the past 7 years highlighting the need for standardized and quantifiable markers to monitor SCD activity, progression, and treatment response.¹ Unity on SCD treatment measures, outcomes, and goals could improve SCD management and patient outcomes.

Aims: To develop a SCD treatment-decision framework that is well-defined, quantifiable, adaptable, personalizable, and clinically relevant for every stage of the individual patient journey.

Methods: SCD experts, from Europe, the Gulf Cooperation Council, and North and South America, with extensive knowledge of specific organ systems commonly associated with SCD-related complications, participated in an iterative series of advisory boards to identify and prioritize how laboratory, clinical, and qualitative measures of SCD activity and progression should be used for treatment decision making. The objectives of the series were to (1) determine quantifiable goals for SCD treatment; (2) identify unmet needs and barriers to applying goal-oriented decision making in SCD clinical practice; and (3) introduce, refine, and validate a SCD treatment decision framework and populate the framework with specific treatment targets. To aid implementation of a SCD treatment-decision framework in clinical practice, parameters identified were prioritized through a virtual survey and differentiated for pediatric or adult implementation.

Results: Advisors highlighted the significance of shared decision making between patient and clinician. Advisors noted treatment goals should be inclusive of biological, social, and psychological dimensions and emphasized that treatment decisions are unique to the individual patient and their experiences. Advisors recommended that a SCD treatment-decision framework should invoke regular assessment, re-assessment, and shared decision making, and proposed the monitoring of three key areas: markers of hemolysis, markers of organ damage, and measures of health-related quality of life (HRQoL). Advisors agreed on the MMR framework (Figure): (1) Manage: Are key SCD parameters managed? (2) Monitor: Are key aspects of disease progression monitored to prevent further organ complications? (3) Realize: Is the patient in a position to fulfill their potential? The MMR framework requires clinicians to consider and reassess the three pillars in parallel in the clinic to assess patient treatment. Advisors identified key assessment criteria: SCD parameters (hematological parameters, markers of hemolysis, presence of vaso-occlusive episodes, presence of acute chest syndrome, transfusion burden, risk of infection); presence and severity of organ complications (renal, cardiovascular, pulmonary, neurological, retinal, osteonecrosis, hepatobiliary, endocrine [growth and development], leg ulcers), and shared decision making (patient treatment goals, HRQoL, pain, fatigue, depression, anxiety, transition of care, reproduction and fertility, professional development).

Summary/Conclusions: The finalized MMR framework should aim to achieve the best clinical standard of care and address worldwide regional limitations. The MMR framework could be used to guide the design of clinical trials. We plan to continuously refine the MMR framework, in partnership with global SCD experts, to allow for customization to worldwide healthcare systems, application to patients based on developmental stage and/or disease status, and to allow piloting in clinical practice.

Topic: 006–Health services and outcomes research including psychology

S. Day¹, Y. Carroll², B. Clemmons¹, K. Powell-Roach¹

University of Tennessee Health Science Center¹, St. Jude Research Hospital²

Background: Sickle cell disease (SCD) is the most common hemoglobinopathy with millions affected globally. However, sickle cell content taught in nursing schools and hospitals is, at best rare and most often nonexistent, resulting in people with SCD receiving care from providers without expertise needed for quality care. Nurses have an opportunity to improve health outcomes and quality of life for people with SCD. Nevertheless, this is not possible without specialized training. To address this critical need, we developed a 5-day Sickle Cell Boot Camp to Promote Nursing Excellence. This initiative provides a unique opportunity for nurses nationwide and globally to gain knowledge and skills in an academic setting taught by pediatric and adult expert instructors.

Methods: SCD nurse experts collaboratively developed a comprehensive curriculum focused on theory and clinical skills and integrated the cornerstones of nursing education, including evidence-based practice, clinical skills, attitudes, and values. All content was peer-reviewed by selected clinical and curriculum experts and revisions applied. After the first boot camp in 2022, the curriculum was expanded to a Train the Trainer Model. Utilizing a Train the Trainer Model, in addition to providing the knowledge and clinical skills, offered the skills and resources necessary to teach the material to other nurses within their institution thus expanding the boot camp's sphere of influence.

Results: Four boot camps have been implemented since 2022 with 110 national and international participants successfully completing the program. A pre/post-knowledge assessment demonstrated statistically significant knowledge improvement when using a paired ttest. Participants completed a comprehensive program evaluation at the end of each day. Results, organized by topic taught and learning objectives, showed participants either strongly agreed or agreed that the learning objectives were met, and open-ended participant comments were very positive. Follow up phone interviews with participants who completed boot camps using the Train the Trainer Model are underway to determine how participants provided SCD education within their institution. Results thus far, include the following initiatives: SCD presentations to staff, media interviews to increase awareness, policy updates, education team created to disseminate SCD information, SCD lunch and learn events, SCD education added to nursing orientation, referrals for children to receive TCD screening, new positions created focused on SCD, presentations at local and national conferences, SCD curriculum implemented in nursing schools, and SCD newsletter for nursing staff.

Conclusion: The boot camps provide critical education across the lifespan of people with SCD, whose lives often depend on nurses' ability to provide quality care and to detect early symptoms of life-threatening complications, and initiate appropriate interventions. Nurses completing the Sickle Cell Boot Camp to Promote Nursing Excellence: Train the Trainer Model have the ability to leverage the reach of the bootcamp and expand knowledge for maximum influence.

1. BW Dyal et al. Reflections of healthcare experiences of African Americans with sickle cell disease or cancer: a qualitative study. Cancer Nursing, 2021; 44(1), E53–E61. doi.org/10.1097/NCC.0000000000000750

2. VM Pinto et al. Vaso-occlusion, hemolytic anemia, and vasculopathy are the hallmarks of SCD pathophysiology. Sickle cell disease: a review for the internist. Internal and Emergency Medicine, 2019; 14(7), 1051–1064. doi.org/10.1007/s11739-019-02160-x

3. Reducing health care disparities in sickle cell disease: a review. Public Health Reports (Washington, D.C.: 1974), 2019; 134(6), 599–607. doi.org/10.1177/0033354919881438

Topic: 006–Health services and outcomes research including psychology

D.D. Dwomoh¹, D.N.Y. Abankwah¹, A.B.A. Benneh-Akwasi Kuma¹, J.M. Spector², J.Q. Quartey¹, O.A. Egbujo³, K.M. Marfo³, S.F.O. Fiifi Ofori-Acquah⁴, J.N. Nonvignon¹

University of Ghana¹, Novartis Biomedical Research², Novartis Pharmaceuticals Corporation³, Sickle Cell Foundation of Ghana⁴

Background: Sickle cell disease (SCD) is a major cause of morbidity and premature deaths in sub-Saharan Africa (SSA).¹ However, SCD management and care have largely been neglected in SSA. In 2019, the Sickle Cell Foundation of Ghana, Ghana Ministry of Health, Ghana Health Services, and Novartis initiated a partnership to establish a framework for tackling priority aspects of SCD management with health system strengthening initiatives to support newborn screening, capacity building to support systems of care and improving access to hydroxyurea (HU). Academic partnership with University of Ghana was commissioned to conduct the monitoring and evaluation (M&E) of the programme.

Aim: This analysis evaluated the effectiveness of HU and its impact on biomarkers, clinical outcomes, and health-related quality of life (HRQoL) among patients (pts) with SCD enrolled in the HU implementation study in Ghana (Ahodwo Programme).

Methods: The M&E study used a rigorous mixed-method process and outcome evaluation plan involving both quantitative and qualitative research designs.² Clinical data were obtained from a HU management mobile application (designed specifically for Ahodwo programme) and pt hospital records to evaluate for biomarkers and clinical outcomes. Additional data such as HRQoL, were obtained from pts and parents/caregiver interviews across 11 SCD centres. Institutional and local investigational review boards and ethics approvals were received before the conduct of the study. Statistical measures were used to describe quantitative and categorical indicators and standard regression models to quantify the impact of HU therapy on SCD biomarkers.

Results: The HU management app included data from 1549 pts who were enrolled in the programme from September 2019 to July 2023. The results from regression models showed that the HU therapy led to a significant increase in haemoglobin levels (Hb) by 0.55 g/dL (95% CI: 0.49–0.61; p < 0.001) among the pts, compared to pre-treatment Hb levels. The number of pts who achieved Hb of ≥10 g/dL also increased by 9.2 percentage points on HU therapy [95% CI: 7.58–10.83; p < 0.001]. The impact of HU on Hb was higher among pts aged >16 years versus <16 years, and among male versus female (Table 1A). HU therapy led to an increase in the mean corpuscular volume and reduction in the absolute neutrophil count, platelets, RBCs, and WBCs, vs pre-treatment period (Table 1A). HbF levels and reticulocyte counts were not measured.

Pts (N = 600; 186 were in Ahodwo) were interviewed from April to November 2023. The incidences of blood transfusion in adults and paediatric pts reduced by 77% and 66%, sickle cell crises by 37% and 65%, rates of hospitalisation by 63% and 64%, and the episodes of malaria by 42% and 59%, respectively (all, p < 0.001) (Table 1B). Also, data revealed positive impact of HU therapy on overall QoL effects among adult and paediatric pts (24% and 44% improvements, respectively), seen as improvements in physical, emotional, social, and school-related functioning, and pain episodes (all, p < 0.01).

Conclusion: To our knowledge, this is the first large-scale real-world implementation of HU outside of a controlled clinical study across SSA. The Ahodwo programme benefited both paediatric and adult pts with SCD, significantly improved their clinical outcomes compared to baseline and had a positive effect on HRQoL. In 2022, the Ghana government announced coverage of HU through its National Health Insurance Scheme.

1. GBD 2021 SCD collaborators. Lancet Haematology, 2023; 10, e585–e599.

2. Moore et al. BMJ, 2015; 350, h1258.

Topic: 006–Health services and outcomes research including psychology

M.W. Farooqui¹, G. Goba¹, L. Hsu¹

University of Illinois¹

Background: Sickle cell disease (SCD) is a genetic disorder affecting red blood cells' oxygen-carrying capacity, causing various health complications. Despite advancements in medical science for SCD patients, disparities persist in women's health issues such as menstrual health. The University of Illinois Hospital houses a prominent sickle cell center catering to over 600 adult patients, with approximately half being women. There are notable gaps in addressing specific women's health needs, as evidenced by chart reviews and patient surveys. A particular focus of concern is the transition through menopause among women with SCD. Similar to a Brazilian study, our site's data suggests that women with SCD may experience premature menopause (46.4 years in SCD vs. 52 years in general population) and that there may be overlapping symptoms between menopause and SCD-related complications. Moreover, clinical diagnosis and management of menopause transition in women with SCD are inadequate, leading to potential health complications and reduced quality of life.

Aims: The primary objective of the study is to implement a rapid menopause screening tool at our Center, ultimately aiming to enhance health outcomes for this population.

Methods: To address this gap in care, the research team is employing implementation science (IS), which aims to bridge the gap between established interventions and their practical application, ensuring widespread adoption and sustainability. This approach also helps identify and overcome barriers to the uptake of interventions.

Results: The project is utilizing the EPIS (Exploration, Preparation, Implementation, Sustainment) framework, which serves as both a process model and a determinants framework, initially focusing on formulating a plan and strategies for successful implementation. In the Exploration phase, needs assessments revealed that menstrual health issues were inconsistently recorded for SCD patients, and interviews with female patients indicated that none had their menstrual health issues addressed by their SCD specialist. Providers did not routinely screen for menopause transition. Although providers expressed interest in screening, they hesitated due to a lack of knowledge regarding the specific needs of women with SCD during menopause transition. Preliminary studies indicated overlapping symptoms between menopause and SCD-related complications, highlighting the need to distinguish between them to avoid misdiagnosis.

To address these challenges, the research team adapted the Menopause Questionnaire 6 (MQ6), a six-question scale commonly used in primary care settings, for use in the SCD population. The MQ6 was chosen for its efficiency and versatility. However, given that the MQ6 was not originally designed for chronic conditions and considering the overlap between menopause and SCD symptoms, the tool was adapted using the ADAPT-ITT model. The adapted questionnaire consists of 10 questions, including 3 additional questions to distinguish menopause transition from SCD symptoms. This adapted questionnaire was piloted at our center for four weeks (April 2024); it took patients about three minutes to complete it.

Screening tool implementation preperation involved stakeholder meetings, where physicians and nurses expressed interest but time constraints as a significant barrier. Stakeholders suggested pre-visit screening via electronic methods like MyChart to overcome barriers. Currently, the team is utilizing a step-up process and piloting the intervention to generate a comprehensive implementation blueprint for clinic-wide implementation prior to embedding for electronic use. Healthcare staff are periodically educated on the screening process. Monthly monitoring through chart reviews will track outcomes, specifically focusing on the completion of the questionnaire and provider actions regarding perimenopausal status.

Post-implementation, a thorough review process will be conducted to identify successes and areas needing improvement. Providers will be interviewed for feedback, and the next phase will focus on sustainment, with plans to expand the screening tool to other sickle cell centers nationwide.

Conclusion: This study is unique in its integration of a well-known sequential model within a process model for implementing menopause transition screening in a vulnerable population. If successful, this approach could serve as a model for implementing other evidence-based practices in low-resource settings, ultimately improving healthcare outcomes for underserved populations.

1. Harlow et al. Disparities in Reproductive Aging and Midlife Health between Black and White women: The Study of Women's Health Across the Nation (SWAN). Womens Midlife Health, 2022; 8, 3.

2. Queiroz et al. Menopause in Brazilian women with sickle cell anemia with and without hydroxyurea therapy. Hematology, Transfusion and Cell Therapy, 2021; 43(3), 386–388.

3. Farooqui et al. Menopause in sickle cell disease: unchartered territory. Blood, 2023; 142, 2509.

4. S Goldstein. An efficient tool for the primary care management of menopause. Canadian Family Physician, 2017; 63(4), 295-298.

5. EPIS Framework. (n.d.). https://episframework.com/

Topic: 006–Health services and outcomes research including psychology

L.M. Shook-Chiles¹, C.B. Farrell¹, L.E. Crosby¹, S.B. Nelson²

Cincinnati Children's Hospital Medical Center¹, Hackman Consulting Group²

Background: Sickle cell disease (SCD) is the most common genetic disorder in the US affecting nearly 100,000 Americans with the majority of patients identifying as Black. Studies have shown individuals with SCD face stigmatization and often receive low-quality care stemming from institutional racism and implicit bias by providers. Provider biases result from a lack of awareness of their own racial identity, failure to develop an anti-racist or social justice lens, and absence of skills to mitigate racist practices/policies.

Aim: The Sickle Treatment and Outcomes Research in the Midwest (STORM) network developed an innovative health equity learning series using the Project ECHO® virtual telementoring model, to educate healthcare providers about implicit bias, racial identity, racism, whiteness, a social justice framework, and strategies for dismantling individual and institutional racist practices.

Methods: Using the Project ECHO© framework,¹ three cohorts were completed with a curriculum that included foundations for racial justice; race; racism; whiteness/white supremacy and white privilege; white normativity; and actions, applications and implementations to dismantle structural racism. Virtual sessions were held via Zoom© and Canvas Learning Management System was used for supplemental learning materials.

Results: There were 32 participants in cohort 1 (81% female, 19% male) with approximately half reporting their racial identity as White (n = 15), Black (n = 11), multi-racial (n = 2) and the remaining (n = 3) not responding. There were 25 participants in cohort 2 (100% female, 0% male) with participants reporting their race as White (n = 18), Black (n = 2), American Indian/Pacific Islander (n = 1); multi-racial (n = 1) and the remaining (n = 3) preferring not to answer. Registrants included physicians, community health workers, nurse practitioners, pharmacists, psychologists, newborn screening coordinators, patient advocates and other multidisciplinary pediatric and adult providers from over 11 US states.

Participants from cohorts 1–2 (n = 23) completed a demographics form and a six-item survey using a five point Likert scale pre- and postlearning series to assess awareness of racism in the US, awareness of racism impacting patients with SCD in the United States, impact of racism on healthcare delivery; provider effectiveness for caring for white patients compared to patients of color; provider feeling equipped to care for patients of color and the impact of racism on provider ability to deliver quality care.

Participants provided qualitative feedback about how the series has impacted their work, changes in practice that will be made as a result of the series, and what they liked best about sessions. Participants noted liked the breakout sessions for deeper discussion; lessons were multifaceted with easily digestible content, there was vulnerability and it was a powerful series. Participants noted the series provided a new perspective and definition to race, racism, systemic racism and white privilege in a safe space to learn from each other.

Awareness of the impact of racism on health care in general as well as specific to SCD increased significantly in all (p = 0.04). There were significant differences in the baseline results between Black and White participants. White participants tended to show greater changes because of training.

Summary/Conclusion: Feasibility and acceptability data from the Health Equity ECHO cohorts suggest this is a promising innovative training platform for multidisciplinary healthcare providers and trainees to raise self-awareness about implicit bias and racism, engage in a safe community of practice for self-discovery, and build skills to address inequities within healthcare settings. It provides an educational platform that is easily accessible and applicable for multidisciplinary healthcare providers to engage in reflection for learning about their own biases.

Future directions include expanding the reach of the learning series.

1. S Arora et al. Academic health center management of chronic diseases through knowledge networks: Project ECHO. Academic Medicine, 2007; 82(2), 154–160.

Topic: 006–Health services and outcomes research including psychology

Mwashungi Ally¹, Deodatus Kakoko¹, Calvin Swai², Emmy Metta¹, Mbonea Yonaz³, Julie Makani¹, Elia Mmbaga⁴, Melkizedeck Leshabari¹, Kåre Moen⁴, Tone Kristen Omsland⁴, Emmanuel Balandya¹

Muhimbili University of Health and Allied Sciences¹, University of Dodoma², Muhimbili National Hospital³, University of Oslo⁴

Background: Sickle cell disease (SCD) is the most common life-threatening monogenic disorder globally.¹ Tanzania is the fifth country with the highest prevalence of SCD globally.² Without comprehensive care, SCD is associated with high morbidity and mortality.^1–3 SCD accounts for 7% of mortality among under-five children in Tanzania.² Hydroxyurea (HU) is a disease modifying drug that reduces the risk of progression to complications related to SCD.⁴ Although HU is available in Tanzania, only 25% of persons with SCD are reported to use it in Tanzania.⁵ Factors contributing to low usage of hydroxyurea include health system factors such as high cost of HU and unavailability of HU in the hospital facilities, and patients and caregivers' factors such as their perceptions of SCD and its medications.⁶ Perceived disease threat is associated with medication usage in patients with chronic diseases. Patients and caregivers with high perceived disease threat have been found to accept the use of medicines and adhere to preventative behaviors.^7–10

Aim: There are no data regarding the association between perceived threat of SCD complications and HU use in Tanzania. In this study, we assessed the factors associated with caregivers' perceived threat of SCD complications and its relationship with HU use among health-insured children with SCD who have access to HU in Dar-es-Salaam.

Methods: We conducted a cross-sectional hospital-based study from May to August 2023. We enrolled 374 caregivers of healthinsured children with SCD from 4 public SCD clinics where HU is available within the hospital facilities and covered by health insurance.

We adapted the modified original and revised Champion's Health Belief Model Scales to derive perceived threat scores. We used Mann–Whitney and Kruskal–Wallis tests for comparisons of the outcomes across sociodemographic characteristics and regression analysis for factors associated with perceived SCD threat.

Results: The median scores (Inter Quartile Range) for perceived threat of SCD complications was 559 (175, 598). Sixty-one percent of caregivers had high SCD perceived threat. The caregivers of under-five children had 141 lower median SCD threat scores compared to those of children aged 13–17 years, p < 0.001. Participants from Regional Referral Hospitals (RRH) had lower median threat scores compared to participants attending Muhimbili National Hospital (MNH), 177 for Amana RRH, 325 Temeke RRH, 585 MNH Mloganzila, and 557 MNH Upanga, p < 0.001. Children of caregivers with high perceived SCD threat were 3.4 times more likely to use HU compared to those with low SCD threat perception (incidence rate ratio 3.4, 95% CI: 2.7–4.5).

Conclusion: Perceived threat of SCD predicts the likelihood of SCD patients using HU in Dar-es-Salaam, Tanzania. A significant proportion of caregivers (40%) have low perceived threat of SCD complication, thus contributing to low usage of HU among their children with SCD in Tanzania. Health education interventions are effective in improving helath literacy, disease knowledge and awareness of SCD.^11,12 We recommend health education to caregivers aiming to improve their SCD threat perception and thus improve the use of HU among children with SCD in similar settings.

1. Inusa et al. International Journal of Neonatal Screening, 2019; 5.

2. Makani et al. PLoS One, 2011; 6(2).

3. Ally et al. Seminars in Hematology, 2023; 60(4), 192–199.

4. Tshilolo et al. The New England Journal of Medicine, 2019; 380(2), 121–131.

5. Ambrose et al. The Journal of Blood Medicine, 2023; (December 2022), 37–47.

6. Kilonzi et al. Hematology, 2021; 2(4), 713–726.

7. Abraham et al. Cambridge Handbook of Psychology, Health and Medicine, 2014; (June 2015), 97–102.

8. CJ Carpenter. Health Communication, 2010; 25(8), 661–669.

9. Asnani et al. The Cochrane Database of Systematic Reviews, 2016.

10. Chen et al. The Journal of Community Health Nursing, 2011; 28(1), 29–40.

11. Houwing et al. Blood, 2019; 134.

12. Ezenwosu et al. Sahel Medical Journal, 2021; 24(1).

Topic: 006–Health services and outcomes research including psychology

J. Chudleigh¹, P. Holder¹, A. Follett²

King's College London¹, Sickle Cell Society²

Background: People from minority ethnic groups,¹ and children and young people^2,3 have inequitable opportunity for involvement in research. The UN Convention on the Rights of the Child⁴ states that children have the right to be involved in matters affecting them, such as having a say in prioritising research questions. Public involvement must be diverse and inclusive to enable research that has the potential to reach those that stand to benefit from it the most, and thus to address issues of health equity¹ and accessibility.⁵ There is limited evidence on optimal models for partnerships in research with children, young people and their families.⁶

Aim: Co-produce resources for inclusive and equitable Patient and Public Involvement and Engagement with children and young people (CYP) with sickle cell disorder (SCD) and their families.

Methods: A sequential qualitative design involving two work packages (WPs):

WP1: Two online workshops; one with CYP with SCD and one with their parents to identify resources needed to facilitate meaningful involvement of CYP with SCD and their families to engage in research.

WP2: Three online workshops with CYP with SCD, their families and researchers to co-produce resources that enable meaningfully engagement in research. A final celebration event to celebrate successes and plan next steps.

Results: CYP and their families identified training and resources needed to facilitate engagement and meaningful involvement in research. An animation was developed, narrated by CYP with SCD, explaining how they would like researchers to engage with them (https://vimeo.com/933352388/aedd90f30a?share=copy). An alternative approach to designing Participant Information Sheets to engage CYP in research was proposed.

Conclusion: CYP with SCD were able to clearly articulate how they want researchers to work with them. Designing alternative resources to engage CYP in research may be beneficial especially for children with serious/life-limiting conditions.

Topic: 006–Health services and outcomes research including psychology

S. Medland¹, J. Bainbridge¹, I. Eastwood¹, S. Mealing¹, M. Cawson², A. Yudina², F. Ola-Adenekan³, O. Bellosanyaolu³

York Health Economics Consortium¹, Terumo BCT², Homerton Healthcare NHS Foundation Trust³

Background: There are approximately 12,500 to 15,000 people living with sickle cell disease (SCD) in England (NICE, 2021). In 2016, recurring automated red blood cell exchange (aRBCX) was routinely commissioned (NICE, 2016) as a treatment for SCD. aRBCX improves control and management of SCD compared to other disease-modifying transfusions (DMTs), namely, manual red blood cell exchange (mRBCX) and top-up transfusions (TUTs). The aim was to analyse the cost-effectiveness of aRBCX compared to other DMTs for adults with SCD at high risk of complications and are ineligible for, refractory to, or unwilling to take pharmacological treatments.

Methods: An individual patient-level simulation model was developed to estimate the cost-effectiveness of aRBCX compared to other DMTs. A heterogenous population of adults was simulated. In each model cycle, individuals received a DMT as per standard treatment schedules. Monte Carlo methods were employed to determine the presence of iron overload following a DMT and whether a chronic or acute complication occurred. Event complication rates, mortality rates and health related quality of life were all dependant on previous complications, in particular the rates of complications were linked to whether or not a vaso-occlusive crisis (VOC) event had occurred.

Iron overload incurred costs for chelation therapy.

Findings from a targeted review informed cost, efficacy, utility, and mortality parameters. Clinical experts were consulted to inform inputs and assumptions where data were sparse. Costs were sourced from national databases and published literature and inflated to 2022/23 where necessary. Costs and benefits were discounted by 3.5% as per NICE guidelines. The deterministic model was run for the total lifetime of 1000 adults to allow for convergence.

Results: Preliminary model results predicted that aRBCX would save the NHS £52,729 and £7653 compared to mRBCX and TUT over an adult's lifetime. Quality-adjusted life years increased by 0.23 in both comparisons. Therefore, aRBCX was cost effective and dominant compared to both mRBCX and TUT. aRBCX had a higher administration cost than TUT but this was offset by the cost of chelation therapy. Thus, presence of iron overload was a key driver of cost effectiveness.

In both comparisons, there was a predicted 21.5% reduction in the lifetime occurrence in VOC events and a 5% reduction in the number of strokes. The use of DMTs over a patient's lifetime was reduced by 49.1% in the aRBCx arm compared to the other two DMTs.

Conclusions: aRBCX allows for more success in achieving clinical targets, improved control of SCD, fewer DMTs, complications, and occurrences of iron overload. aRBCx is also likely to be cost-effective compared to other DMT options.

Future analysis will investigate the cost-effectiveness of aRBCX in the paediatric population and in other settings, including France and African countries.

1. National Institute for Health and Care Excellence (NICE). How common is sickle cell disease? July 2021. https://cks.nice.org.uk/topics/sickle-cell-disease/background-information/prevalence/

2. National Institute for Health and Care Excellence (NICE). Spectra Optia for automatic red blood cell exchange in people with sickle cell disease. Medical technologies guidance [MTG28]. March 2016. https://www.nice.org.uk/guidance/mtg28

Topic: 006–Health services and outcomes research including psychology

N.M. Archer¹, A. Power-Hays², E.A. Hendry³, M. Valentino³, M. Hall⁴, K.E. Kyler⁵, J.W. Antoon⁶, S. Tang Girdwood², J. Goldman⁵, A. Morel⁵, T.J. Savage⁷, L.E. Orth⁸, A.M. Jenkins³

Boston Children's Hospital¹, Cincinnati Children's Hospital Medical Center², University of Rochester Medical Center³, Children's Hospital Association⁴, Children's Mercy Kansas City⁵, Vanderbilt University Medical Center⁶, Brigham and Women's Hospital⁷, University of Colorado Skaggs School of Pharmacy⁸

Background: National societies including the American Society of Hematology recommend ketamine, an N-Methyl-D-Aspartate receptor antagonist, as an opioid-sparing adjunct for the treatment of refractory pain in sickle cell disease (SCD). Little is known regarding how it is being used nationally to treat hospitalized individuals with SCD.

Aims: To describe ketamine use over time and examine associations between ketamine use and healthcare utilization outcomes in patients with SCD admitted to children's hospitals.

Methods: We performed a multi-center cross-sectional study of individuals ≥6 months with SCD admitted to a Pediatric Health Information System (PHIS) contributing children's hospital (n = 43) from 2016 to 2022. We used ICD-10 diagnosis codes to identify SCD hospitalizations, excluding those with OR charges, direct admits, or transfers. Our outcome of interest was ketamine use during hospitalizations. To determine if ketamine use was associated with outcomes (i.e., length of stay (LOS), any cause 14-day readmission, parenteral opioid use during hospitalization), we used generalized estimating equations adjusting for patient demographics, hospital, hydroxyurea use and number of SCD related hospitalizations in the year prior as a proxy for SCD severity. We also tested whether early (≤72 h) versus late (>72 hours) ketamine use during admission was associated with hospital outcomes.

Results: 15,261 children and young adults with SCD had a total of 64,545 hospitalizations. Ketamine was used in 2809 (4.3%) (Table 1). Ketamine use increased from 2.3% of hospitalizations in 2016 to 5.9% in 2022 (p < 0.001). Factors most associated with ketamine use included older age and most recent years (Figure 1). Ketamine was associated with longer LOS, readmission, and parenteral opioid days, but also greater hydroxyurea use and number of hospitalizations in the year prior. Early versus late ketamine use was associated with shorter LOS (6 days [IQR 4,9] vs. 12 [IQR 9,16]) and less parental opioid days (4 [IQR 2,7] vs. 9 [IQR 6,13]).

Summary/Conclusion: While ketamine was used in less than 5% of hospitalized children and young adults with SCD, its use has more than doubled over 10 years. In those treated with ketamine, the association with decreased LOS and days on parenteral opioids with early compared to late ketamine use calls for randomized control studies to determine patients that would benefit most from ketamine use and if early initiation should be standard of care.

1. Schwenk et al. Regional Anesthesia & Pain Medicine, 2018; 43, 456.

2. Brandow et al. Blood Advances, 2020; 4, 2656.

Topic: 006–Health services and outcomes research including psychology

Spencer Mackie¹, Bridget Chivers¹, Teswaree Sewdin¹, Tung Le¹, Cynthia Lee¹, Sophie Newman¹, Asad Luqmani¹, Mamta Sohal¹, Mark Layton¹, Steven Okoli¹

Imperial College Healthcare NHS Trust¹

Background: Sickle cell disease (SCD) is an inherited anaemia caused by a point mutation in the β-globin gene. The disease is characterised by numerous acute and chronic complications and, due to limited treatment options, remains a life-limiting condition with significant morbidity.

The Non-Malignant Haematology Clinical Trials Unit (CTU) was set up in 2015 to facilitate the delivery of SCD clinical trials and research studies at Hammersmith Hospital, London, United Kingdom (UK). Embedded within the Imperial College Healthcare NHS Trust, a specialist haemoglobinopathies coordinating centre (HCC), the CTU is composed of 4 clinicians, 3 nurses, and 3 practitioners. To date, the team has now delivered 13 SCD clinical trials and 4 research studies, offering individuals with SCD the opportunity to try new disease-modifying agents and actively take part in research to advance the understanding of the disease. To facilitate this work, the team has looked to encourage engagement and participation in SCD clinical trials and research studies.

Aims: This study aims to describe and review the strategies implemented by the CTU to improve recruitment to SCD clinical trials and research studies.

Method: In 2022, the CTU introduced several strategies to drive engagement and participation in SCD clinical trials and research. These included: (i) embedding 2 practitioners in the SCD outpatient clinic to build rapport with patients, address queries, and introduce research, (ii) delivering presentations at SCD patient participation groups and patient days and (iii) presenting active SCD clinical trials in weekly, local SCD multi-disciplinary team meetings and monthly HCC multi-disciplinary team meetings.

Results: After implementing the above strategies, the Non-Malignant Haematology CTU has seen several successes. The team has become the first CTU in the UK to recruit to Purpose, Rise-Up and Crosswalk-C – 3 global, multi-centre SCD clinical trials. It has also achieved recent success in a national, multi-centre study, REDRESS, delivering the third adult haploidentical haematopoietic stem cell transplantation in the UK.

The above strategies have also improved recruitment to the CTU's SCD research studies. In 2021, 1-year pre-implementation, recruitment to the biobank project NIHR Rare Disease BioResource Haemoglobinopathies (NIHR-RD-BR HBP) and quality of life study RUDY were 0.42 and 0.16 patients per month, respectively. In 2023, 1-year post-implementation, recruitment to both studies increased significantly to 7.92 and 0.75 patients per month, respectively. As of 2024, 52.08% (238 patients) of the Hammersmith Hospital-SCD cohort are now participating in the NIHR-RD-BR HBP project, and 8.53% (39 patients) in RUDY.

Conclusion: The challenges associated with recruiting to SCD clinical trials and research are complex, but education and facilitation are key to improving patient participation. To this end, the Non-Malignant Haematology CTU will continue to prioritise its strategies to aid the development of better therapeutic options and outcomes for people with SCD.

1. DC Rees et al. Sickle-cell disease. Lancet, 2010; 376(9757), 2018–2031.

2. A Lal et al. S103: trial in progress: a phase 2, open-label study evaluating the safety and efficacy of the PKR activator etavopivat (FT-4202) in patients with thalassemia or sickle cell disease. Hemasphere, 2022; 6(Suppl), 2. doi:10.1097/01.HS9.0000821380.12178.0d

3. MJ van Dijk et al. One-year safety and efficacy of mitapivat in sickle cell disease: follow-up results of a phase 2, open-label study. Blood Advances. 2023; 7(24), 7539-7550. doi:10.1182/bloodadvances.2023011477

4. M Callaghan et al. P120: trial in progress: the randomized, double-blind, placebo-controlled phase 2 A crosswalk-c trial evaluating the efficacy of crovalimab as adjunct treatment in the prevention of vaso-occlusive episodes (VOES) in patients (PTS) with sickle cell disease (SCD). Hemasphere, 2022; 6(Suppl), 27-28. https://classic.clinicaltrials.gov/ct2/show/NCT05392894, https://bioresource.nihr.ac.uk/media/2bxdxuyn/web-summary-hbp-v1-2-18052022.pdf, https://www.rudystudy.org/

Topic: 006–Health services and outcomes research including psychology

C.N. Mosley¹, A.C. Lang¹, K. Smith-Whitley², A.A. Thompson², C.M. Barriteau³, L. Schwartz², L.M. Shook-Chiles¹, L.E. Crosby¹

Cincinnati Children's Hospital Medical Center¹, Children's Hospital of Philadelphia², Ann and Robert Lurie Children's Hospital³

Background: Children and adults with sickle cell disease (SCD) are at increased risk of hospitalization and death due to COVID-19 infection. Nevertheless, there is hesitancy among SCD patients and their families to receive a COVID-19 vaccine and a desire for tailored education from healthcare professionals. Recent research examining COVID-19 vaccine attitudes, beliefs, and intentions revealed rates of intention were low to moderate even though most patients perceived the COVID-19 vaccine as safe to get (Shook et al., 2024). Moreover, patients and their families reported that their primary source of trustworthy information about vaccines was their doctor/clinician, and preferred method for learning about COVID-19 vaccines was videos from sickle cell leaders and experts. The current project utilized a community-engaged research approach to examine adolescent patients with SCD and caregivers' educational needs and perspectives about COVID-19 vaccines and develop educational materials.

Methods: Participants were adolescents (12–17 years old) with SCD, adults (18 years old and older) with SCD, and parents/primary caregivers of a child (0–17 years old) with SCD. Phase 1 involved five focus groups and one interview (n = 17). A directed content analysis of the data was used to code transcripts and identify themes. Utilizing results from Phase 1, an educational website and clinician communication talking points were developed. Phase 2 involved 2 additional focus groups and one additional interview with patients and caregivers (n = 8) to give feedback on the website which was used to iteratively refine the website.

Results: Phase 1 interview and focus groups confirmed quantitative results suggesting that participants' primary trusted source of COVID-19 vaccine-related information was their hematology team. Participants' top concerns were side effects and limited research of the COVID19 vaccine(s) in the SCD population. Major influences for getting vaccinated included provider recommendation, to increase protection and decrease worry about COVID-19, and the ability to resume normal activities. This data was then used to create clinician communication talking points and a publicly available educational website. The following information can be found on the website: (1) COVID-19 and the development of vaccines/boosters, (2) COVID-19 and flu similarities and differences, (3) SCD-specific information (e.g., medication considerations, precautions, etc.), and (4) topics to consider when discussing COVID-19 vaccines/boosters with your clinician. The format included bullet points and tables, brief (5–7 min) educational videos from sickle cell specialists and an individual living with SCD, and links to reliable resources consistent with educational pReferences: noted in Phase 1.

The website and talking points were refined several times based on feedback from Phase 2 interview/focus groups. During the final group, participants reported that were highly likely to use the site when discussing vaccines with family, friends, and/or their healthcare team (100%). Participants also reported that the most important aspect of the website was that the information was SCD-specific and included the voice of an SCD Warrior.

Conclusions: Taking a community-engaged research approach to developing educational materials ensured that they were rigorous and relevant, aligned with the needs and preferences: of those in the SCD community. It is hoped that the educational materials will increase the exposure of the SCD community to reliable medical information about COVID-19 vaccines and SCD.

1. Shook et al. Journal of Pediatric Hematology/Oncology, 2024; 10-1097.

Topic: 006–Health services and outcomes research including psychology

Coralea Stephanou¹, Petros Kountouris¹, Celeste Bento², Cornelis L. Hartveld³, Jan Traeger-Synodinos⁴, John S. Waye⁵, Zhiyu Peng ⁶, Irene Fylaktou⁴, Hashim Halim-Fikri⁷, Tamara T. Koopmann³, Landry Nfonsam⁵, Jun Sun⁶, Kyriaki Michailidou¹, Marina Kleanthous¹, Thessalia Papasavva¹, Zilfalil Bin Alwi⁷, Carsten W. Lederer¹

The Cyprus Institute of Neurology & Genetics¹, Centro Hospitalar e Universitário de Coimbra², Leiden University Medical Center³, National and Kapodistrian University of Athens⁴, Hamilton Health Sciences, McMaster University⁵, BGI Genomics⁶, Universiti Sains Malaysia⁷

Background: Accurate and consistent interpretation of sequence variants is essential for delivering safe and reliable diagnostic genetic services. Determining variant pathogenicity depends on establishing the strength of the relationship between the gene in which it occurs and the associated disease. Until recently, there has been a lack of a formal and universally agreed-upon framework for defining the clinical relevance of genes and variants in precision medicine and research. This gap is now being addressed by the Clinical Genome Resource (ClinGen) Consortium. In its first pilot, the ClinGen Hemoglobinopathy Variant Curation Expert Panel (VCEP)¹ is evaluating the adaptation of the ClinGen framework for hemoglobinopathies. The VCEP is validating the role of genes in hemoglobinopathies, while also testing gene- and disease-specific modifications to the ACMG/AMP guidelines for variant interpretation.

Aim: To test the VCEP-specified ACMG/AMP guidelines for variants, determine disease entities and validate gene-disease associations in hemoglobinopathies.

Methods: Rule specifications were piloted on 48 globin variants in the genes HBB (β-globin locus, NG_000 007), HBA2, and HBA1 (αglobin locus, NG_000006), previously submitted to ClinVar. These variants covered different types and classifications. Disease selection followed recommendations by the Hemoglobinopathy VCEP, developed with guidance from the ClinGen Lumping and Splitting Working Group.² Throughout this process, the VCEP reviewed the molecular mechanism, mode of inheritance, and phenotypic variability across associated hemoglobinopathies to determine if existing assertions required revision (either lumped together or split apart). The ClinGen General Gene Curation Expert Panel (GCEP) conducted an evaluation of the gene-disease associations proposed by the VCEP, which considered genetic and experimental evidence, including case-level evidence for rare variants provided by the VCEP, aligned with the ClinGen clinical validity framework.

Results: The Hemoglobinopathy VCEP developed disease-specific rules for variant classification, resulting in 31 unique evidence codes, some with varying levels of strength based on available evidence. The pilot study tested 84% (26/31) of the rules and reclassified 46% of variants (22/48), with the remainder having the same annotations as ClinVar. Benign variants were often reclassified as uncertain significance (VUS) due to insufficient (14%, 3/22) or conflicting (18%, 4/22) evidence. Among discordant variants, 67% (6/9) were resolved as Likely Benign (17%, 1/6) or VUS with insufficient evidence (83%, 5/6). Three VUS with conflicting evidence were reclassified as Pathogenic using a Bayesian framework. The VCEP defined eight disease terms for HBB and six disease terms for HBA2 and HBA1. At the time of curation, eight, two, and three gene-disease pairs reached definitive, moderate, and limited clinical validity classifications, respectively.

Conclusions: The Hemoglobinopathy VCEP specifications received approval from ClinGen in April 2021 (Step 2 approval), initiating further validation and adaptation for additional known globin gene variants in a pilot study (towards Step 3 approval). This study highlights the importance of integrating established gene-disease associations into clinical genetic testing and emphasizes the essential role of standardized expert specifications of the ACMG/AMP guideline for interpreting globin gene variants as a crucial step towards achieving comprehensive globin variant classification.

1. P Kountouris et al. Human Mutation, 2021; 43(8), 1089–1096.

2. C Thaxton et al. Cell Genomics, 2022; 2(5), 100131.

1. I Okpala et al. The comprehensive care of sickle cell disease. The European Journal of Haematology, 2002; 68, 157–162.

2. M de Montalembert et al. Sickle cell disease: a comprehensive program of care from birth. Hematology American Society of Hematology Education Program, 2019; 2019 (1), 490–495.

3. LL Mulumba, L Wilson. Sickle cell disease among children in Africa: an integrative literature review and global recommendations. International Journal of Africa Nursing Sciences, 2015; 3, 56–64.

4. N Galadanci et al. Current sickle cell disease management practices in Nigeria. International Health, 2014; 6(1), 23–28.

5. C Hoppe, L Neumayr. Sickle cell disease: monitoring, current treatment, and therapeutics under development. Hematology/Oncology Clinics of North America, 2019; 33(3), 355–371.

6. C Oyedeji, JJ Strouse. Improving the quality of care for adolescents and adults with sickle cell disease—it's a long road. JAMA Network Open, 2020; 3(5), e206377.

7. G Arch et al. Attitudes toward management of sickle cell disease and its complications: a National Survey of Academic Family Physicians. Anemia, 2015; 2015(13), 1–6.

8. ME Houwing et al. Improving access to healthcare for paediatric sickle cell disease patients: a qualitative study on healthcare professionals' views. BMC Health Services Research, 2021; 21:229.

Topic: 001–Basic and translational

C.C. Efobi¹, C.A. Nri-Ezedi², H.C. Okoye³, B. Nwogoh⁴

Department of Haematology and Blood Transfusion, Faculty of Basic Clinical Sciences, Nnamdi Azikiwe University, Nnewi Campus¹, Department of Paediatrics, Faculty of Medicine, Nnamdi Azikiwe University, Nnewi Campus², Department of Haematology and Immunology, College of Medicine, University of Nigeria Teaching Hospital, Ituku Ozalla Campus³, Department of Haematology and Blood Transfusion, University of Benin, Edo State⁴

Background: Sickle cell disease (SCD) is a hereditary multisystemic disorder endemic to Sub-Saharan Africa, characterized by high morbidity and mortality rates. The ABO blood group system has been implicated in various diseases. Investigating the relationship between ABO blood groups and the clinical manifestations of SCD could facilitate risk stratification, particularly in resource-limited settings.

Aim: To determine the impact of ABO blood group on the clinical manifestation of SCD.

Methodology: This prospective cohort study was conducted among consenting SCD patients at the Department of Haematology, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Nigeria. Demographic data, ABO blood group information, frequency of crises, history of blood transfusions, complications, and laboratory results (including full blood count, kidney function tests, and liver function tests) were collected. Patients were stratified using a sickle cell severity score based on their ABO blood group. Descriptive statistics were used to summarize demographic characteristics. Categorical variables were analyzed using chi-square or Fisher's exact tests, and continuous variables were assessed using t-tests or Mann–Whitney U tests for non-normally distributed data. A p < 0.05 was considered statistically significant.

Result: The study cohort comprised 62 patients, with 38 (61.3%) males and an average age of 29.0 ± 8.0 years. Blood group distribution was as follows: O (46 patients, 74.2%), A (12 patients, 19.4%), and B (4 patients, 6.5%). The majority (50 patients, 80.6%) experienced 0-2 vaso-occlusive crises annually (p = 0.010). Patients with blood group B exhibited the highest severity scores (5.6 ± 1.1), while those with blood group A had the lowest (3.2 ± 2.7), although this difference was not statistically significant (p = 0.129). Notably, despite the small sample size of blood group B, the majority (3 out of 4, 75%) had severe disease compared to other groups, yet this observation was not statistically significant (p = 0.551). Furthermore, blood group B patients presented with the highest total white cell counts (15.8 ± 6.7), whereas blood group A patients had the lowest (8.7 ± 5.3) (p = 0.026). The platelet-to-neutrophil ratio was highest in blood group A (101.9 [46.9–141.4]) and lowest in blood group O (69.1 [48.2–118.9]), though this finding was not statistically significant (p = 0.361).

Summary: Patients with blood group B demonstrated worse clinical outcomes compared to those with other blood groups, while blood group A patients had the most favorable outcomes.

Conclusion: These findings underscore the necessity for larger, multicenter studies to validate these observations, which could enhance risk stratification and early detection of complications in SCD patients.

Topic: 001–Basic and translational

C. Njuguna¹, C. kilach¹, F. Njuguna², E. Ayaye¹, C. Wanjiku¹, R. Korir¹, C. Bor¹, N. Midiwo¹, E. Aliwa¹, E. Oburah¹, S. Mbunya¹, J. Kipkoech¹, M.A. Etling³, T.S. Saverance⁴, C.N. Nessle⁵, T. Vik⁶, M. Kumar⁷, C. Roberson⁷, A. Greist⁷

Academic Model Providing Access to Healthcare (AMPATH)¹, Moi University², Fogarty International Center, National Institute of Health, Bethesda, MD, USA³, University of Missouri, School of Medicine, USA⁴, University of Michigan, Department of Pediatrics, Division of Hematology/Oncology, Ann Arbor, MI, USA⁵, Indiana University, USA⁶, Indiana Hemophilia and Thrombosis Centre, USA⁷

Background: Globally, approximately 515,000 infants with sickle cell disease (SCD) are born every year. Approximately 80% of these cases occur in Sub-Saharan Africa (SSA) annually including 14,000 new-borns in Kenya. In SSA, 50%–80% of children will die before the age of 5 years due lack of comprehensive SCD care compared to 3% in better-resourced settings.

Aim: We aim to highlight the Academic Model Providing Access to Healthcare (AMPATH) SCD Program efforts to mitigate the morbidity and mortality of SCD in Western Kenya through its evolution in strengthening training, awareness, screening, advocacy and access to care.

Methods: The Academic Model Providing Access to Healthcare (AMPATH) SCD Program started in 2010 as a partnership between Moi University, Moi Teaching and Referral Hospital (MTRH), and Indiana Hemophilia and Thrombosis Center (IHTC) to improve access to comprehensive SCD care by increasing capacity through training, clinical care, research, and advocacy.

Results/Discussions: The program has trained over 5000 healthcare workers on different aspects of SCD through face-to-face instruction, virtual training, and one-on-one mentorship programs. Early infant screening for 14,700 under-fives and support for access to medications like hydroxyurea and antibiotics through a revolving funds pharmacy model has been key in improving clinical care and outcomes. The program has also participated in several research projects, for example, validation of point-of-care SCD screening tests and a clinical trial evaluating the effectiveness of daily proguanil (the standard of care), monthly sulfadoxine/pyrimethamine plus amodiaquine, or monthly dihydroartemisinin-piperaquine as malaria prophylaxis in individuals with SCD. It has been a strong advocate for the provision of comprehensive SCD care by the health facilities within the high SCD burden areas in Kenya and responsive policies by the Ministry of Health. In addition, the program has helped patients/caregivers to establish support groups for psycho-social support and sharing.

Conclusion/Recommendation: After more than a decade of collaboration, engagement, and research, there is an established Comprehensive SCD clinic in Moi Teaching and Referral Hospital (MTRH) with a network of clinics throughout Western Kenya. The AMPATH Hematology Program pillars of education and training, care and collaboration, and research and innovation have effectively empowered locals to continue improving care for individuals with SCD in Western Kenya. This model can serve as a replicable framework to disseminate across SSA and in other resource-limited settings around the world.

Topic: 001–Basic and translational

G. Ometto¹, G. Montesano², R. Awadzi¹, L. Mandalapu¹, M. Almusawy¹, D.P. Crabb², C. Dinah¹

London North West University Healthcare NHS Trust¹, City University of London²

Background: Sickle cell maculopathy, characterized by retinal thinning and nonperfusion, is detectable through advanced imaging techniques like optical coherence tomography (OCT) and OCT-angiography (OCT-A). Despite the high prevalence of these ocular manifestations, there are few studies investigating the functional impact of the retinal thinning seen on OCT in sickle maculopathy.

Aims: To delineate the relationship between retinal vascular density, retinal thinning, and functional sensitivity in patients with sickle cell disease (SCD).

Methods: A single-site, cross-sectional, observational study was conducted with 27 patients diagnosed with sickle cell maculopathy at the Brent Sickle Centre. Participants underwent swept source domain OCT and OCT-Angiography OCT-Angiography (Triton, Topcon Healthcare, Japan) to assess retinal structure and vessel density, coupled with microperimetry (Compass, iCare, Italy) to evaluate retinal sensitivity. A custom application¹ analysed OCT-A scans to locate the anatomical fovea, guiding perimetric test coordinates (Figure 1). Linear mixed-effect models predicted the impact of structural and vascular parameters on retinal sensitivity. Significant changes in the goodness of fit were determined with a likelihood-ratio test (LRT). R² were calculated using fixed effect predictions.

Results: There was a significant relationship between structural parameters (inner retinal thickness, IRT, and vessel density from OCT-A) and retinal sensitivity (p < 0.0001). Figure 2 shows that models incorporating both IRT and OCT-A data, provided better sensitivity prediction (R² = 0.48) than those using either IRT or OCT-A alone (R² = 0.39 or 0.22, respectively). All differences in R² between models were statistically significant (LRT p < 0.001).

Summary/Conclusions: This study highlights the use of a structurally aligned perimetric test to standardise performance of microperimetry and improve the spatial structure-function correspondence. We demonstrate the importance of including OCT-angiography in predicting functional impact in sickle cell maculopathy.

Topic: 001–Basic and translational

H.K. Khan¹, V.P. Panjwani¹, H.J. Al-Jahdami², M.R.B. Boulassel²

Sultan Qaboos University Hospital¹, Sultan Qaboos University²

Background: Continuous efforts are being made to identify new biomarkers in sickle cell disease (SCD) to foster a realistic expectation of clinical outcomes and to tailor therapeutic approaches. One of the biomarkers could be circulating microparticles (MPs), as they were involved in the pathogenesis of SCD. Herein, we characterized MPs in a well-defined cohort of SCD patients, by assessing their cellular origin and their usefulness as a tool to help improve the management of SCD patients.

Materials and Methods: This was a prospective longitudinal study, in which SCD patients in steady state attending the outpatient clinics were randomly enrolled. The absolute concentrations of circulating platelet MPs (PLT MPs) and red blood cell MPs (RBC MPs) were assessed by flow cytometry using an optimized protocol. Associations among levels of MPs, clinical severity, spleen status, hypercoagulability markers, transfusions, hydroxyurea use, hemoglobin F levels, glucose-6-phosphate dehydrogenase (G6PD) status and blood ABO types were investigated.

Results: A total of 140 SCD patients and 30 healthy age and sex matching controls were enrolled. The age of patients ranged from 2 to 63 years and 48.6% were females. Levels of MPs were higher in patients compared to controls (p < 0.0001). Levels of PLT MPs and RBC MPs were higher in splenectomized patients compared to not-splenectomized patients (p = 0.001). Levels of MPs remained elevated after several months of follow-up. Weak associations were evidenced among levels of MPs, age, gender, clinical severity score, hydroxyurea therapy, hemoglobin F, and co-existence of G6PD deficiency.

Conclusion: The concentrations of PLT and RBC MPs in SCD patients differ markedly from those in healthy subjects. MPs levels were significantly increased in splenectomized patients, but they were not related to sociodemographic data, treatment modifiers, and clinical severity scoring system. Collectively, these findings highlight the need for further characterization of MPs originating from other cell types in SCD patients to elucidate their role in disease pathogenesis.

1. AH Al-Salem. ISRN Hematology, 2011; 2011, 864257.

2. SM Camus et al. Blood, 2015; 125, 3805–3814.

3. RP Hebbel et al. British Journal of Haematology, 2016; 174, 16–29.

4. VA Ferraris. The Journal of Thoracic and Cardiovascular Surgery, 2015; 149, 312–313.

5. LJ van Tits et al. Biochemical and Biophysical Research Communications, 2009; 390, 161–164.

6. EJ Van Beers et al. Haematologica, 2009; 94, 1513–1519.

7. A Piccin et al. Journal of Extracellular Vesicles, 2015; 4, 28414.

8. Y Garnier et al. PLoS One, 2017; 12, e0177397.

9. MR Boulassel et al. Human Immunology, 2022; 83, 818–825.

10. W Kheansaard et al. Scientific Reports, 2018; 8, 13033.

11. VA Morikis et al. Frontiers in Immunology, 2021; 12, 663886.

Topic: 001–Basic and translational

R.D.A. Almabadi¹, L.D. Doi², C.C. Chandler²

University of Edinburgh/King Saud University¹, University of Edinburgh²

Background: In the Kingdom of Saudi Arabia (KSA), the burden of SCD is high, as evident by the high prevalence of more than 45,100 per 1,000,000 adults. SCD is more prevalent in the country's eastern and southern areas. However, SCD poses unique challenges for university students in KSA. Understanding their experiences and perceptions within the university environment is crucial for developing effective self-management strategies for this population.

Aim: As part of a project to develop a self-management toolbox for university students with SCD in KSA, this qualitative study aims to explore the experiences and perceptions of university students with SCD in the eastern and southern regions of KSA. Specifically, it seeks to elucidate the challenges faced, the self-management and coping strategies employed, and the impact of the disease on academic pursuits within the university context. For the purpose of this abstract, the focus is on the initial semi-structured interviews conducted with participants.

Methods: Eight semi-structured interviews were conducted so far with university students diagnosed with SCD in the eastern and southern regions of KSA (5 females, 3 males, 6 from the east, and 2 from the south). Participants were recruited from two universities in the south and east of KSA. Interviews were audio-recorded, transcribed verbatim, and analyzed thematically using NVivo software. Preliminary themes were identified iteratively through constant comparison between interviews.

Results: The study revealed several preliminary key findings; participants described striving for normalcy while navigating the challenges of SCD within the university environment. Several factors influencing the trajectory of pain crises were identified, including their unpredictability and associated complications, emphasizing the need for effective management strategies and early recognition of warning signs. Support from family, peers, and religious beliefs played vital roles in coping with SCD-related challenges. Significantly, several participants described the continued challenges youth with SCD face in terms of stigmatization and psychosocial impacts. Themes of acceptance, resilience, and self-management emerged prominently, with participants reflecting on their journey from shame to proactive disease management. Overall, participants demonstrated high awareness and acceptance of their condition, viewing their experiences as motivators for academic success. However, participants from the south and east reported varying disease experiences based on contextual factors.

Conclusion: This study provides valuable insights into the multifaceted challenges faced by university students with SCD in the eastern and southern regions of the KSA and the diverse self-management strategies and coping mechanisms employed to navigate these challenges. Findings underscore the importance of tailored interventions, increased awareness, and holistic approaches to care within educational settings to foster inclusivity and empower students with SCD. By understanding and addressing the unique needs of students with SCD, effective self-management interventions can be developed to support university students with SCD in living an efficient and normal life.

Topic: 001–Basic and translational

D.D.B. Dwuma-Badu¹, C.S. Segbefia², K.A.A. Amega-Aho³

Korle-Bu Teaching Hospital¹, University of Ghana Medical School, College of Health Sciences², School of Medicine, University of Health and Allied Sciences³

Background: Hydroxyurea (HU) is the primary medication for modifying sickle cell disease (SCD) due to its availability and cost-effectiveness compared to newer treatments. In Ghana, HU was initially available only as 500mg capsules, which had to be compounded into suspension for children needing lower doses or who had difficulty swallowing capsules. For many years, the suspension was available at only one centre in Ghana's capital city, Accra, posing accessibility and other challenges for caregivers. In July 2022, dispersible tablets (100 and 1000 mg) were introduced on the Ghanaian market. However, there is limited information about caregivers' experiences with these tablets since their introduction.

Aims: This study explores the experiences of caregivers of Ghanaian children with SCD regarding the use of dispersible HU tablets.

Methods: A mixed-methods approach was employed, combining quantitative and qualitative data. In May 2024, caregivers of children with SCD who had experience with both the suspension prepared from HU capsules and dispersible HU tablets were interviewed using a semi-structured questionnaire. Data collected included patients' demographics, haemoglobin phenotype, information on tablet use (duration, funding, and acquisition), and caregivers' experiences. Responses were analyzed using thematic analysis.

Results: Interviews were conducted with 30 caregivers. Table 1 summarizes patients' characteristics and experience with dispersible HU tablets. Key themes identified include accessibility, administration, convenience, compliance, storage, and cost. The suspension was challenging due to its limited availability, preparation difficulties, and refrigeration requirements, leading to missed doses and restricted travel. In contrast, dispersible tablets were easier to access and administer, improved compliance, and eliminated the need for refrigeration, simplifying storage and travel. Despite twice the cost of tablets to suspension, caregivers preferred the tablets for their overall ease of use and reliability.

Conclusion: Caregivers favour dispersible tablets over suspension despite the higher cost, primarily due to their convenience and reliability. Recommendations include increasing the availability of dispersible tablets.

Topic: 001–Basic and translational

I. Thomas¹, R. Maharaj², R.M. Maharaj³, M. Berghs⁴, K. Atkin⁵, A. Hogan⁶, C. Nicholls⁶, J.F.W. Willson-Pepper³

Sickle Cell Society¹, UK Thalassaemia Society, 19 The Broadway, London, UK², UK Thalassaemia Society³, De Montford University⁴, University of York⁵, NHS England Screening Programmes⁶

Background: Sickle cell and thalassaemia are severe, genetic blood conditions which disproportionately affect people of African, South Asian and Middle Eastern heritage. The NHS Sickle Cell and Thalassaemia screening programme offers screening antenatally to identify carriers, facilitate early specialist counselling and offer prenatal diagnosis. Newborn screening is offered for SCD only, but can usually identify beta thalassaemia major as a biproduct.

Aims - Learning from Service Users: A Sickle Cell Society and UK Thalassaemia Society joint project aimed to understand how health professionals communicate screening results and support service users, to help improve health access and outcomes.

Methods: The Societies organised, recorded and analysed focus group discussions and one-to-one interviews with 36 people service users falling into two categories: mothers and fathers of children aged three or under with SCD, thalassaemia or carrier status, and individuals considering having children.

Results and Conclusion: Implications for health practice.

The focus groups uncovered both poor and positive user experiences in relation to disclosure of results, timeliness, language, stigma, knowledge and understanding. Participants were impacted by a haemoglobinopathy screening diagnosis and needed clear, sensitive, informed communication, in the context of awareness about ethnic differences and inequalities, and religious and cultural beliefs.

The findings have been reported¹ and presented to midwives, health visitors, and nurse specialist counsellors, and are contributing to a revision of NHS screening training and guidance.²

1. R Maharaj, I Thomas. It's In Our Genes https://ukts.org/3d-flip-book/its-in-our-genes/ April 18, 2023. Accessed June 6, 2024.

2. NHS Sickle Cell and Thalassaemia Screening Programme (2012) Guidance–Sickle cell disease: report screening results to parents (https://www.gov.uk/government/publications/sickle-cell-disease-report-screening-results-to-parents)

Topic: 001–Basic and translational

W.R. Rozi¹, A.R. Rahhal², M.Y. Yassin³

Rochester Regional Health¹, Hamad Medical Corpotation², Hamad Medical Corporation³

Introduction: Venous thromboembolism (VTE) in sickle cell disease (SCD) is associated with a two to four times increase in mortality risk compared to SCD patients without VTE. Nevertheless, the evidence guiding the management of VTE in SCD is scarce. Therefore, we conducted a systematic review and meta-analysis to evaluate direct oral anticoagulants (DOACs) effectiveness and safety in SCD.

Methods: We performed a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the English literature for randomized controlled trials, observational studies, reviews, case series, and case reports for DOACs use in VTE treatment in SCD. The odds ratios (OR) were calculated for recurrent VTE and major bleeding. The Q test and I² were used to examine heterogeneity, with I² > 50% indicating marked heterogeneity.

Results: We identified a total of 7 articles: four observational studies, and three case series addressing this matter with a total of 236 patients. Three studies (n = 172) were included in the meta-analysis, with 88 SCD patients receiving DOACs and 84 receiving warfarin. The use of DOACs was associated with a similar reduction in VTE recurrence compared to warfarin (OR = 1.03, 95% CI: 0.5–2.10, I²= 0%). However, DOACs use significantly reduced major bleeding (OR = 0.16, 95% CI: 0.04–0.59, I²= 0%).

Conclusion: The results of this systematic review and meta-analysis are reassuring in showing a decreased major bleeding rate of DOACs compared to VKA in patients with SCD while maintaining equivalent effectiveness.

1. JB Herrick. Yale Journal of Biology and Medicine, 2001;74(3), 179.

2. CT Quinn. Experimental Biology and Medicine (Maywood), 2016; 241(7), 679–688.

3. M Nasimuzzaman et al. Blood Advances, 2019; 3(20), 3170–3180. doi:10.1182/BLOODADVANCES.2019000193

Topic: 001–Basic and translational

Authors: A.R. Rassouli¹, M.C. Castillo¹, M.F. Farooqui¹

Affiliations: University of Illinois-Chicago¹

Background/Aims: Sickle cell disease (SCD) is a chronic condition characterized by recurrent vaso-occlusive episodes (VOEs) that cause significant morbidity. While advancements have been made, treatment options remain limited. Crizanlizumab, approved by the FDA for reducing VOEs in individuals aged 16 and older, recently faced scrutiny following the Phase III STAND study, which failed to show a significant reduction in VOEs compared to placebo in the European Union. Consequently, there is growing concern among U.S. providers regarding crizanlizumab. This study aims to evaluate the impact of crizanlizumab discontinuation on VOEs requiring healthcare visits.

Methods: This study is a single institution retrospective chart review of all individuals who received crizanlizumab between October 2020 and March 2024. Dara collected included age, gender, sickle cell subtype, crizanlizumab initiation and discontinuation dates, reasons for discontinuation, and the number of emergency department, acute care, and hospital visits in the 24 months before initiation and up to 24 months after discontinuation.

Results: Fourteen patients met the study criteria; four with ongoing crizanlizumab treatment were excluded, leaving ten patients for analysis. Key findings include:

Overall VOE Visits: Patients experienced fewer VOE visits while on crizanlizumab, with a continued reduction in admissions post-discontinuation compared to the 24 months preceding initiation.

Subtype Analysis: Individuals with the HbSC subtype benefited most, exhibiting the longest duration of treatment and the greatest reduction in hospitalizations (Table 1).

Gender Analysis: Female patients demonstrated a more significant reduction in median visits while on treatment compared to males (Chart 1).

Statistical Analysis: There was no statistically significant difference in the monthly rate of hospitalizations between pre- and post-crizanlizumab periods. However, patients had the lowest median hospitalization rates during treatment.

Charts and Tables

Table 1: Analysis of hospitalizations dependent on sickle cell subtype.

Chart 1: Median Monthly Hospitalization by Gender.

Summary: The findings suggest crizanlizumab effectively reduces VOE-related hospital visits during treatment, with some continued benefits observed post-discontinuation. This effect was most pronounced in patients with the HbSC subtype and among females. The study underscores the importance of careful monitoring and management of treatment discontinuation, as patients may still experience reduced VOE frequency even after stopping crizanlizumab.

Conclusion: The treatment of SCD remains challenging with a pressing need for more effective and accessible therapies. This study highlights that while crizanlizumab discontinuation did not lead to an increase in VOEs, the medication did provide substantial benefits during its use in our cohort. Continued research and a nuanced understanding of treatment impacts are crucial for optimizing patient outcomes in SCD.

Implications for Practice

Patient Monitoring: SCD providers should carefully monitor patients discontinuing crizanlizumab to ensure continued management of VOEs.

Personalized Treatment: Consideration of subtype and gender may guide more personalized treatment plans.

Further Research: Ongoing studies are needed to explore the long-term impacts of discontinuation and to develop new therapies for SCD.

Topic: 001–Basic and translational

E. Cunha¹, I. Barreiros¹, L. Relvas¹, J. Pereira¹, J. Gomes¹, T. Maia¹, C. Bento¹

University Hospital Coimbra, Portugal¹

Background: Sickle cell disease is the most common structural hemoglobinopathy throughout the world and results from a point mutation with substitution of the 2nd nucleotide of the 7th codon of the HBB gene, which encodes the β globin chain, leading to replacement of the amino acid glutamic acid by valine. Consequently, valine induces a hydrophobic attraction in the hemoglobin molecule (Hb) between adjacent β chains leading, when in the homozygous state, to polymerization of Hb molecules and inducing a change in the shape of erythrocytes. This change leads to cellular dehydration, increased hemolysis and abnormal interactions with other cells of plasma. In addition to being homozygous for the variant (HbS/HbS), there are other forms of sickle cell disease, in which only one of the alleles produces HbS, with trans inheritance of other HBB mutations. Several additional changes may be present on the other allele, such as β-thalassemia or Hb variants. It has gradually emerged that are more than 15 different genotypes that can cause SCD.¹ The clinical manifestations of each of these sickle cell syndromes are distinct from each other, and the associated complications vary in severity.

Aims: Identify the different forms of chromatographic presentation of sickle cell disease, and, in association with the genetic study, evaluate the prevalence of compound heterozygosity, Hb S with another variant, in patients with sickle cell disease followed in our laboratory.

Methods: Retrospective analysis of patients who underwent a hemoglobin study by HPLC (Bio-Rad VARIANT II Beta-Thalassemia Short Program) with subsequent genetic study of β-globin variants by Sanger sequencing and/or MLPA, in cases clinically suspected of sickle cell disease.

Results: From January 2023 to April 2024, in a total of 2200 HPLC performed, 88 new patients with sickle cell disease were identified. Most of them only have HbS and Hb F in HPLC (79), the others are: HbS/HbC (6), HbS/HbD (1), HbS/Hb Lepore (1) and HbS/HbE (1). Molecular characterization of the HbS/HbS like samples revelead that 74 are Hb S homozygous, 3 are compound heterozygous HbS/β^{IVSI-110(G>A)} thal, 2 are compound heterozygous HbS/β^IVSI-1(G>A) thal and 1 is compound heterozygous HbS/β^Del thal.

Conclusion: Sickle cell disease is the most common monogenic disease worldwide, with a higher prevalence in Sub-Saharan African countries, Mediterranean Basin, Middle East and India. In Portugal there is no registry of patients with sickle cell disease and the estimated number is around 2000.² The most frequent compound heterozygous states found in this study are HbS /HbC and HbS/β thal. However, due to the increasing migratory flows, new genotypic associations have been observed and is very important to consider them. According to our results, where in 15 months we found 8 different genotypes, the number of different genotypes that can cause SCD will increase to much more than the 15 expected. Apart form hemoglobin studies (which can be carried out by HPLC or capillary electrophoresis) and their correlation with hematological parameters and clinical and family history, molecular studies are of extreme importance for a correct sickle cell disease diagnosis.

Topic: 001–Basic and translational

S.M. Spencer¹, M.P. Player¹

Nottingham University Hospitals Trust¹

Haemoglobin Sabine is an unstable haemoglobin characterised by substitution of leucine to proline at codon 91 of the beta globin gene.¹ Autosomal recessive inheritance leads to a form of chronic haemolytic anaemia where cases reported thus far have presented with varying degrees of clinical severity and managed with ad hoc and regular transfusions, folic acid and splenectomy. We present a case of a 30 year old patient managed currently on a regular transfusion programme alongside hydroxycarbamide.

Our patient was initially misdiagnosed as Hb Koln in childhood and underwent a splenectomy at age 10 due to massive splenectomy resulting in a mild subsequent compensated haemolysis. In 2013 he started to experience episodes of priapism which initially settled without treatment. In 2015 an unstable haemoglobin was detected on HPLC not in keeping with Hb Koln and subsequent DNA analysis revealed heterozygosity for Hb Sabine along with an xmn1 polymorphism and heterozygosity for the 3.7 kb single alpha globin deletion.

Due to increased episodes of priapism, he was started on 50 mg Sildenafil in 2019. Subsequently he developed gradually worsening symptomatic anaemia Hb 65 g/L in 2020 which was initially managed with an automated red cell exchange programme and switched to regular top-up transfusions in 2021 when hydroxycarbamide was commenced. He is also on deferasirox for iron chelation. His Hb F% has improved form 3.9% to 6% after 2 years, though he has not yet achieved maximum tolerated dose (MTD).

This case highlights the long term management of a patient with Hb Sabine using hydroxycarbamide which has not been reported before in literature. Hydroxycarbamide induces Hb F synthesis and higher levels may be indicative of a milder clinical picture in Hb Sabine, though there is a paucity of information regarding the long-term management of these patients. Kollia et al.² reported a patient with an HbF of 12.8% who had no typical symptoms of Hb Sabine. The patient with the highest Hb F % found on a search of literature (16.5%) was splenectomised at age 5 but significant transfusion requirement was not documented³. The index case had an F% of 12 and maintained an Hb of 85 to 106 g/L post splenectomy.⁴ The only case with an Hb F of 0% required monthly transfusions.⁵

Our case describes an effective method for the long-term management of persons with Haemoglobin Sabine.

Topic: 001–Basic and translational

N. Dieng¹, M. Diaw², S.B. Gning¹, S. Diop³, A. Samb²

Internal Medecine Departement Hopital Principal de Dakar¹, Laboratory of Human Physiology, Faculty of Medicine, Pharmacy and Odontology, Cheikh Anta Diop University², Clinical Hematology Service, National Center for Blood Transfusion (CNTS)³

Introduction: Recurrent vaso-occlusive crises (VOCs) and chronic hemolysis contribute to chronic arterial involvement in sickle cell disease. This study aimed to evaluate vascular stiffness by comparing SS and SC individuals during the inter-critical phase.

Methods: We conducted a cross-sectional study including 74 patients with sickle cell disease (37 SS; 37 SC) followed at the National Center for Blood Transfusion (CNTS). Vascular stiffness was assessed using pOpmetre to measure finger-toe Pulse Wave Velocity (ft-PWV) and Flow Mediated Dilation (FMD) using Doppler ultrasound. In both groups, we evaluated the annual frequency of vaso-occlusive crises (VOCs), the presence of chronic complications, and cardiovascular and biological parameters.

Results: Mean ft-PWV was respectively 6.2 m/s for SS and 5.9 m/s for SC (p = 0.36). Mean blood velocities before and after compression were 77.3 and 127.6 cm/s for SS, and 78.1 and 115.8 cm/s for SC, with respective p-values of 0.94 and 0.34. The kinetics curves of FMD were similar in both groups. Ft-PWV was positively correlated with age in both groups (SS: p = 0.02, r = 0.38; SC: p = 0.01, r = 0.43) and with chronic complications (p = 0.02, r = 0.39) in the SC phenotype.

Conclusion: Vascular stiffness impairment was similar in both patients with SS and SC sickle cell disease despite more common cardiovascular complications occurring in the SS phenotype.

1. Ranque et al. Circulation, 2016; 134(13), 923–933.

2. Dubert et al. La Revue de la Médecine Interne, 2015; 36(Suppl 2), SA95.

3. Lemogoum et al. Hypertension, 2004; 44, 924–929.

4. Raitakari et al. The British Journal of Clinical Pharmacology, 2000; 50(5), 397–404.

Topic: 002–Novel therapies, gene therapies, bone marrow transplant and emerging diagnostics

A.M. Hovhannisyan¹, L.S. Sahakyan², M.S. Badikyan², H.S. Khachatryan²

Genetic Forensic Center LLC¹, “Yeolyan” Hematology and Oncology Center Ministry of Health²

Aims: Thalassemia is a group of common hereditary anemias that cause significant morbidity and mortality worldwide, particularly in Southeast Asian, Middle Eastern, and Mediterranean populations (Taher et al. 2017). The precise diagnosis of thalassemia, especially rare variants, remains challenging. This abstract aims to present an overview of the thalassemia genetic diagnostics overall and the current state and future direction of genetic diagnostics of thalassemias in Armenia.

Methods: This study reviews European Molecular Genetics Quality Network (EMQN) Best Practice Guidelines, Thalassaemia International Federation (TIF) report and existing publications for thalassemias control policies and genetic testing approaches, with a focus on their application in Armenia, as well as review of existing a few publications from Armenia on thalassemias.

Results: According to the TIF report, there is an urgent need for pilot studies to promote control policies and develop appropriate services nationwide. Preventive services for hemoglobin (Hb) disorders, including thalassemia, rely primarily on population screening, counseling, and prenatal diagnosis. These pilot studies may require collaboration with international centers that possess the necessary technology and expertise, emphasizing the importance of international networking. Effective planning for thalassemia control must consider the genetic and clinical heterogeneity of the syndromes. This requires detailed micro-mapping, high-quality genetic screening data, prevalence and birth incidence of carriers, and comprehensive local clinical information, all of which are essential for directing services effectively.

According to the EMQN Best Practice Guidelines and existing publications, diagnosing thalassemias and abnormal hemoglobin variants involves a combination of first-line laboratory tests (Traeger-Synodinos et al. 2015). These include measuring red blood cell indices with automatic hematology analyzers, hemoglobin analysis, and quantification of Hb A2 and Hb F. High-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) systems are crucial for distinguishing thalassemic diseases from carriers. These systems offer both qualitative and quantitative analyses of Hb components with high precision and reproducibility, allowing for rapid prenatal and postnatal diagnoses of thalassemia (Farmakis et al. 2022).

Genotyping for specific thalassemia mutations is carried out using real-time polymerase chain reaction (PCR) followed by melting curve analysis (Munkongdee et al. 2020). If mutations cannot be identified using standard molecular techniques, DNA sequencing is performed. Additionally, next-generation sequencing (NGS) has been increasingly applied for thalassemia diagnosis in recent years (Peng et al. 2022).

In Armenia, the only available data regarding thalassemias come from a study assessing carrier frequencies in Armenia and Georgia, involving 202 unselected Georgian and 190 unselected Armenian subjects (C. Oberkanins et al., 2021). This study, utilizing PCR technology, concluded that carrier frequencies appear to be low, suggesting thalassemias may not be a major health concern in these countries. However, these conclusions are based on limited data and the lack of comprehensive first-line genetic testing capabilities.

Summary/Conclusion: Given the limited scope of carrier testing and the lack of comprehensive first-line genetic testing in Armenia, it is premature to definitively conclude that thalassemias are not a significant health concern. There is a need for pilot study and more extensive data and the implementation of more accurate technologies to substantiate this claim, especially considering evidence from local clinical reports and smaller-scale studies that suggest a higher prevalence of thalassemia cases than currently documented. Specifically, reports from local health professionals indicate that there are unreported cases and misdiagnoses due to inadequate diagnostic facilities, highlighting the need for improved genetic testing infrastructure and more comprehensive epidemiological studies.

In conclusion, to accurately assess and address the state of thalassemias in Armenia, it is imperative implementation of advanced genetic diagnostic technologies according to the international guidlines and broader data collection to provide a clearer picture of thalassemia's impact in Armenia, suggesting a more dynamic and ongoing approach to genetic health monitoring in the region.

Topic: 002–Novel therapies, gene therapies, bone marrow transplant and emerging diagnostics

H. Frangoul¹, F. Locatelli², A. Sharma³, M. Bhatia⁴, M. Mapara⁵, L. Molinari⁶, D. Wall⁷, L. Dedeken⁸, R.L. Liem⁹, A.J. Shah¹⁰, P. Telfer¹¹, S. Corbacioglu¹², D. Rondelli¹³, M. Cavazzana¹⁴, R. Meisel¹⁵, M. Eckrich⁶, S. Lobitz¹⁶, M. de Montalembert¹⁷, M. Steinberg¹⁸, M.C. Walters¹⁹, L. Bower²⁰, S. Imren²⁰, C. Simard²⁰, F. Xuan²⁰, W. Zhou²⁰, P.K. Morrow²¹, W. Hobbs²⁰, S.A. Grupp²²

Sarah Cannon Research Institute at The Children's Hospital at TriStar Centennial¹, IRCCS, Ospedale Pediatrico Bambino Gesù Rome, Catholic University of the Sacred Heart², Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital³, Department of Pediatrics, Columbia University Irving Medical Center⁴, Department of Medicine, Division of Hematology/Oncology, Columbia University⁵, Sarah Cannon Pediatric Transplant and Cellular Therapy Program at Methodist Children's Hospital⁶, The Hospital for Sick Children/University of Toronto⁷, Hopital Universitaire des Enfants Reine Fabiola⁸, Ann & Robert H. Lurie Children's Hospital of Chicago⁹, Stanford University¹⁰, Royal London Hospital, Barts Health NHS Trust¹¹, University of Regensburg¹², University of Illinois at Chicago¹³, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), University of Paris¹⁴, Division of Pediatric Stem Cell Therapy, Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty¹⁵, Gemeinschaftsklinikum Mittelrhein¹⁶, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), University of Paris-Cité¹⁷, Boston University Chobanian & Avedisian School of Medicine¹⁸, UCSF Benioff Children's Hospital¹⁹, Vertex Pharmaceuticals Incorporated²⁰, CRISPR Therapeutics²¹, Children's Hospital of Philadelphia and Perlman School of Medicine, University of Pennsylvania²²

Background: Exagamglogene autotemcel (exa-cel) is a non-viral cell therapy that reactivates fetal hemoglobin via ex vivo CRISPR-Cas9 gene-editing of autologous CD34+ hematopoietic stem and progenitor cells (HSPCs) at erythroid-specific enhancer region of BCL11A. Exa-cel is approved as a one-time treatment for patients (pts) with severe sickle cell disease (SCD) based on positive results from a pre-specified interim analysis of the CLIMB-THAL-111 phase 3 trial.

Aims: Evaluate longer-term efficacy and safety of exa-cel in pts with SCD.

Methods: CLIMB SCD-121 is a 24-month (mo), phase 3 trial of exa-cel in pts age 12–35 years with SCD and a history of ≥2 VOCs/y in 2 years prior to screening. Enrollment and dosing are complete; trial is ongoing. Primary efficacy endpoint is proportion of pts free of severe VOCs for ≥12 consecutive mos (VF12); key secondary efficacy endpoint is proportion of pts free from inpatient hospitalization for severe VOCs for ≥12 consecutive mos (HF12). Pts evaluable for VF12 and HF12 had ≥16 mos follow-up after exa-cel infusion. Evaluation of primary and key secondary endpoint began 60 days after last RBC transfusion for post-transplant support or SCD management. Pts completing trial enrolled in long-term follow-up Study 131. Mean (SD) shown except where noted.

Results: As of 19 March 2024, 46 pts with SCD (age 21.4 [range 12–34] y; 12 [26.1%] age ≥12 to <18 years; 4.2 VOCs/y at baseline) received exa-cel; median follow-up 28.4 (range 8.2–57.4) mos. 31 pts completed 2 years of follow-up in CLIMB SCD-121 and enrolled in Study 131. All pts engrafted neutrophils and platelets (median 27 and 34.5 days, respectively). 36/39 (92.3%) pts evaluable for primary endpoint were free of VOCs for ≥12 consecutive mos (VF12; 95% CI: 79%, 98%) and 38/39 (97.4%) were free from hospitalizations for VOCs for ≥12 consecutive mos (HF12; 95% CI: 87%, 100%). In pts achieving VF12, VOC free duration was 27.9 (range 12.5-54.8) mos. 33/36 pts remained VOC free; 1 pt had an adjudicated VOC after parvovirus infection ~22.8 mos after exa-cel (pt recovered and has been VOC-free [21.6 mos]) and 2 pts had VOCs assessed as due to psychosocial stressors after 30.5 mos and 29.9 mos of being VOC-free (pts have since been VOC-free for 7.1 and 3.3 mo). For all pts, mean total Hb was 11.9 g/dL at Month 3 and ≥11.0 g/dL from Month 6 onward; mean HbF was 37.4% at Month 3 and generally ≥40.0% from Month 6 onward with pancellular distribution (≥95% RBCs express HbF). Proportion of edited BCL11A alleles was stable in bone marrow CD34+ and peripheral blood nucleated cells. Quality-of-life (QOL) measures showed clinically significant improvements from baseline.

All pts had ≥1 adverse event (AE), most were Grade 1 or 2; 46 (100%) pts had AEs of Grade 3 or 4 severity. Most common AEs were nausea (69.6%), stomatitis (63.0%), vomiting (58.7%), febrile neutropenia (54.3%), headache (54.3%), and abdominal pain (52.2%). Most AEs and serious AEs (SAEs) occurred within first 6 mos. No pts had SAEs considered related to exa-cel. One pt died from respiratory failure due to COVID-19 pneumonia unrelated to exa-cel. There were no study discontinuations or malignancies.

Conclusions: Exa-cel treatment led to early and sustained Hb and HbF increases, eliminating VOCs in ~92% of pts, eliminating inpatient hospitalization for VOCs in ~97% of pts, and improving QOL, which was maintained over the longer term for up to 5 years. Safety profile remains generally consistent with myeloablative busulfan conditioning and autologous transplantation. These results confirm the potential for exa-cel to provide a one-time functional cure to pts with severe SCD.

1. Frangoul et al. The New England Journal of Medicine, 2024; 390, 1649–1662.

Topic: 002–Novel therapies, gene therapies, bone marrow transplant and emerging diagnostics

S.T. Tomashvili¹

High Technology Medical Centre¹

Background: Non-transfusion-dependent thalassemia (NTDT) encompasses a spectrum of thalassemia syndromes characterized by ineffective erythropoiesis, chronic anemia, and iron overload that does not necessitate regular blood transfusions. Patients with NTDT experience significant morbidity due to complications such as hepatosplenomegaly, skeletal abnormalities, and progressive iron overload, which can lead to liver and cardiac dysfunction. Current treatment options, primarily aimed at managing symptoms and iron overload, include occasional transfusions, iron chelation therapy, and splenectomy. However, these treatments have limitations and side effects, underscoring the need for novel therapeutic approaches that target the underlying pathophysiology of the disease.

Aims: This study aims to explore and evaluate emerging therapeutic strategies targeting erythropoiesis and iron metabolism in NTDT. These include JAK2 inhibitors, hepcidin modulation, apo-transferrin therapy, and targeted fetal hemoglobin induction, all of which have shown potential in preclinical models.

Methods: Preclinical studies using NTDT mouse models (th3/+ and th1/th1) were reviewed to assess the efficacy of JAK2 inhibitors, hepcidin modulators, apo-transferrin, and targeted fetal hemoglobin induction. These models exhibit characteristics akin to human NTDT, such as non-transfusion-dependent anemia, hepatosplenomegaly, and iron overload. The therapeutic effects were evaluated based on parameters including erythropoiesis, splenomegaly, iron levels, and overall hematologic improvement.

Results: JAK2 Inhibitors: In th3/+ mice, JAK2 inhibitors significantly reduced erythroid hyperplasia and splenomegaly by decreasing ineffective erythropoiesis. These effects were achieved with minimal impact on red blood cell synthesis, suggesting potential benefits in avoiding splenectomy and related complications in NTDT patients. Preliminary clinical studies with ruxolitinib, a JAK2 inhibitor, have shown promising results in reducing spleen size and improving hemoglobin levels with a tolerable safety profile.

Hepcidin Modulation: Hepcidin overexpression in th3/+ mice led to reduced iron content in the liver and spleen, higher hemoglobin levels, and decreased reticulocyte counts. Hepcidin therapy could manage iron loading and ameliorate erythroid pathologies in NTDT. Clinical trials with hepcidin mimetics and TMPRSS6 inhibitors have demonstrated efficacy in reducing iron overload and improving anemia in patients with iron loading anemias.

Apo-Transferrin: Daily injections of apo-transferrin in th1/th1 mice resulted in increased hemoglobin levels, normalized red blood cell survival, reduced splenomegaly, and improved erythroid maturation. Apo-transferrin also enhanced hepcidin expression, reducing circulating non-transferrin bound iron and iron overload. Early-phase clinical trials have indicated that apo-transferrin can improve erythropoiesis and reduce iron overload in patients with NTDT.

Targeted Fetal Hemoglobin Induction: Recent molecular investigations have identified promising targets for inducing fetal hemoglobin, such as BCL11A, MYB, and KLF1. Interfering with fetal hemoglobin silencing, particularly through BCL11A inactivation, has shown success in correcting sickle cell disease in adult mice. Small molecule inhibitors targeting the epigenetic partners of these factors are in development, potentially offering new therapeutic avenues for NTDT and other hemoglobinopathies. Preliminary data from gene editing studies targeting BCL11A in patients have shown increased fetal hemoglobin levels and clinical improvement.

Summary/Conclusion: The potential of JAK2 inhibitors, hepcidin modulation, apo-transferrin therapy, and targeted fetal hemoglobin induction represents a promising advancement in the treatment of NTDT. These novel therapeutic strategies target the underlying causes of ineffective erythropoiesis and iron overload, offering hope for more effective and safer management options. Preclinical studies have demonstrated significant improvements in key disease parameters, and early clinical data are encouraging. Ongoing and future clinical trials will be crucial in confirming these findings and establishing the safety and efficacy of these therapies in NTDT patients. If successful, the integration of these novel approaches could transform the therapeutic landscape for NTDT, providing patients with improved prognosis and quality of life.

Topic: 002–Novel therapies, gene therapies, bone marrow transplant and emerging diagnostics

C. Segbefia¹, Y. Dei-Adomakoh¹, E. Mensah², P. Thota³, A. Peprah⁴, D. Dwuma-Badu⁴, I. Odame⁵

Korle Bu Teaching Hospital/University of Ghana Medical School¹, University of Ghana Medical School², Hemex Health³, Korle Bu Teaching Hospital⁴, The Hospital for Sick Children/University of Toronto⁵

Introduction: Sickle cell disease (SCD) is a group of inherited disorders of haemoglobin (Hb) synthesis, first described in the medical literature by James Herrick in 1910. According to a Lancet study published in June 2023, 515,000 babies were born with sickle cell disease (SCD) in 2021, with more than three quarters of those births in sub-Saharan Africa. In Ghana, approximately 2% of newborns have SCD (corresponding to almost 16,000 infants with SCD born per year), 98% of whom are genotypes SS and SC. Epidemiological modeling indicates that broad implementation of sickle cell disease (SCD) screening could save the lives of up to 9.8 million newborns by 2050. The World Health Organization (WHO) estimates that 70% of SCD deaths are preventable with early diagnosis of SCD coupled with comprehensive care. In resource rich countries, SCD newborn screening (NBS) performed in centralized laboratories has led to substantial reduction in SCD mortality.

SCD NBS requires sensitive detection of low levels of certain hemoglobin (Hb) variants (i.e., sickle Hb, HbS) in presence of high levels of other Hb variants (i.e., fetal Hb, HbF). The current centralized tests used for NBS for SCD employ high performance liquid chromatography (HPLC) and isoelectric focusing. However, in sub-Saharan Africa and central India, where >90% of annual SCD births occur, implementation of NBS programs has been challeniging due to the cost as well as technical and logistical burden. Consequently, there remains a need for affordable, portable, user-friendly and accurate point-of-care (POC) diagnostic tests to facilitate decentralized Hb testing in limited-resource settings for enabling nationwide NBS.

Methods: A total of 379 newborn babies were enrolled in the study from the postnatal ward of the Department of Obstetrics and Gynecology at Korle Bu Hospital, Accra, Ghana which handles about 8000 deliveries a year. Blood samples were collected via heel prick and tested on Gazelle and compared to High-performance liquid chromatography (HPLC).

Results and Discussion: Gazelle yielded a high diagnostic accuracy for all Hb variants compared to standard laboratory tests (HPLC). Sensitivity was 100% for disease versus normal and disease versus trait and, 96.6% for trait versus normal. Specificity was 99.7% for disease versus normal, 100% for disease versus trait, and 95.3% for trait versus normal. Gazelle Hb Variant displayed an overall diagnostic accuracy of 98.4% in comparison to reference standard methods for all Hb variants.

Table: Summary of true positive, true negative, false positive, false negative, sensitivity, and specificity of the clinical testing among newborns conducted at Korle Bu Teaching Hospital, Accra, Ghana.

Conclusion: Gazelle enables cost-effective and rapid identification of common Hb variants in newborns at the point-of-need. Overall, Gazelle is a versatile point-of-care system that enables affordable, accurate, rapid, decentralized NBS for SCD in resource-limited settings where the prevalence for SCD is high. A simplified version of the cartridge is in development which has fewer number of steps of operation with a quick turnaround time and can further facilitate the screening process.

1. GBD 2021 Sickle Cell Disease Collaborators. The Lancet Haematology, 2023; 10, e585–e599.

2. B Aygun, I Odame. A global perspective on sickle cell disease. Pediatric Blood & Cancer, 2012; 59(2), 386–390.

3. K Ohene-Frempong et al. Screening newborns for sickle cell disease in Ghana. Pediatrics, 2008; 121(Supplement), S120–S121.

4. D Jain et al. Sickle cell disease: current challenges. Journal of Hematology & Thromboembolic Diseases, 2015; 3, 224. doi:10.4172/2329-8790.1000224

5. OS Olatunya et al. Perceptions and practice of early diagnosis of sickle cell disease by parents and physicians in a Southwestern State of Nigeria. Scientific World Journal, 2020; 2020, 4801087. doi:10.1155/2020/4801087

6. NS Green et al. The Consortium on Newborn Screening in Africa for sickle cell disease: study rationale and methodology. Blood Advances, 2022; 6(24), 6187–6197. doi:10.1182/bloodadvances.2022007698

7. DL Wethers. Sickle cell disease in childhood: part II. Diagnosis and treatment of major complications and recent advances in treatment. American Family Physician, 2000; 62(5), 1013–1020.

Topic: 002–Novel therapies, gene therapies, bone marrow transplant and emerging diagnostics

A. Lai¹, K.Z. Summers¹, O. Agrippa¹, M. Yusuf¹, T. Singh¹, K.A. Anie², P. Telfer³, S. Lugthart⁴

Sanius Health¹, London North West University Healthcare NHS Trust², Barts Health NHS Trust³, University Hospitals Bristol and Weston NHS Foundation Trust⁴

Background: Sickle cell disease is an inherited blood disorder characterised by sickle-shaped red blood cells due to a mutation in haemoglobin, resulting in severe pain and organ damage. Exagamglogene autotemcel (exa-cel) is the first approved CRISPR-Cas9 gene editing therapy for SCD. It has shown efficacy in reducing vaso-occlusive crises (VOCs) in 97% of patients and hospital admissions in 100% of patients.

Aims: To gain insights into patient awareness, knowledge and interest in gene therapy for SCD, and to identify challenges associated with treatment access.

Methods: An online survey was completed by 94 SCD patients aged 16 to 65 in November 2023, covering patient characteristics, therapy awareness, information sources, treatment decision-making factors, concerns and access barriers related to gene therapies. This data was then linked to patient-reported outcomes and medical record data (VOCs/complications) within a real-world SCD data ecosystem to examine potential eligibility for gene therapies.

Results: A summary of the patient cohort characteristics is given in Figure 1. The largest proportion of respondents were between 24 and 34 years old (27%), with the HbSS genotype being most prevalent (76%). Based on a high-level cohort assessment, with key Exa-cel criteria (aged >12 years, HbSS, with recurrent VOCs), it is estimated that 28% (26) would potentially be eligible for gene editing. Further complications-based data from medical records of 19 of these patients was used to assess transplant eligibility criteria, indicating a potential 17% (16) of patients might be eligible based on an absence of ICD-10 codes linked to major complications such as kidney dysfunction, liver dysfunction, or cardiovascular issues.

Despite nearly half of patients (49%) having limited/no awareness of gene editing and only 23% and 26% aware of exa-cel and ongoing gene therapy trials, respectively, 72% were very interested in learning more about gene editing for curative SCD treatment. While over 10% were uncertain about gene therapy outcomes, the most desired impacts were crisis reduction (24%), a complete cure (18%) and improved quality of life (14%).

Access to treatments like gene editing was rated as ‘very important’ by 54% of patients. However, critical barriers to access were identified (Figure 2), which included treatment costs and funding to ensure availability (53%).

Currently, most patients primarily receive information regarding medical advancements via healthcare professionals (66%), online resources (46%) and social media (45%). Moreover, they expressed a preference for learning about gene therapy through different approaches including patient forums/support groups (83%), clinically led workshops (83%).

Although 23% reported no concerns about gene editing, safety remained the greatest concern for many (26%), including side effects, complications, and adverse events. Over half (56%) felt insufficiently informed about the risks-benefits ratio. This sentiment was highlighted by identifying safety (46%) as the top factor in treatment decisions. In supporting their decision-making around gene therapy, patients emphasised the importance of beneficial evidence including first-hand experiences shared by past patients (22%), general statistics (16%), scientific evidence (13%) from studies demonstrating long-term safety, efficacy, and outcomes.

Summary/Conclusions: Challenges such as low awareness of gene therapy and critical barriers to access were identified in this work, highlighting the need for patient education and engagement to facilitate the delivery of novel therapies to SCD patients. Generating evidence on key topics such as safety and risk-benefit ratios can guide future engagement strategies and support treatment decision-making, and patient-to-patient experience sharing was flagged as particularly important in this process. This work therefore supports the curation of future routes to accelerate tackling of patient concerns and current barriers to access.

Topic: 002–Novel therapies, gene therapies, bone marrow transplant and emerging diagnostics

A. Lai¹, K.Z. Summers¹, O. Agrippa¹, M. Yusuf¹, K.A. Anie², P. Telfer³, S. Lugthart⁴

Sanius Health¹, London North West University Healthcare NHS Trust², Barts Health NHS Trust³, University Hospitals Bristol and Weston NHS Foundation Trust⁴

Background: Sickle cell disease (SCD) is an inherited blood disorder, characterised by acute and chronic complications such as vaso-occlusive crises (VOCs) that cause 95% of hospital admissions. Transfusion is a core standard of care for SCD complications but can lead to adverse side effects. Novel therapies, Crizanlizumab and Voxelotor, received approval in the US for SCD treatment in 2019; Crizanlizumab has demonstrated efficacy in reducing pain, frequency and time to VOCs, while Voxelotor has been shown to increase haemoglobin levels and decrease haemolysis.

Aims: To generate a better understanding of real-world patient experiences and health outcomes with Crizanlizumab and Voxelotor, by exploring clinical measures such as haemoglobin (Hb) levels, frequency of transfusions, VOCs and hospital admissions.

Methods: An online survey with questions regarding patients' characteristics, experiences with transfusion and novel therapies (Voxelotor/Crizanlizumab), VOC occurrences, and hospital admissions was conducted (February-April 2024). In total, 58 SCD patients in the US completed the survey.

Results: In the overall cohort (n = 58), HbSS was the most common genotype (62%), followed by HbSC (21%) and HbS Beta 0 Thalassemia (9%). The mean (SD) recent haemoglobin level was 8.9 (±2.4) g/dL. 13 (22%) patients were receiving Voxelotor, 9 (16%) Crizanlizumab, and 4 (7%) both treatments at the time of the survey. 24 patients (41%) had never received either treatment. 45 patients had received blood transfusions, with 19 (33%) patients reporting receiving regular transfusions (defined as every ≤6 weeks). 44/55 (80%) patients had received hydroxyurea (HU), with 17/54 (31%) being HU intolerant.

In the Voxelotor group, with a mean (SD) treatment duration of 379.7 (±512.3) days, the mean Hb level was 8.7 (±3.3) g/dL pre-treatment initiation and 9.6 (±2.7) g/dL post-treatment initiation (Figure 1A). For those treated for over 365 days, the mean rate of VOCs per year was 3.4 (±2.5) (Figure 1B). 85% of patients had been admitted to the hospital at least once since beginning treatment, primarily due to VOCs (38%) and general disease symptoms (23%) (Figure 1C). Blood transfusions were administered to 92% of patients and 85% had been receiving them regularly, with the most common transfusion intervals being every 2 months or less (42%) and every 3–6 weeks (33%). Post-Voxelotor initiation, the mean number of transfusions received over 12 months decreased from 5.3 to 3.0.

Mean (SD) treatment times for the Crizanlizumab-treated group was 442.7 (±414.2) days. The mean Hb level was 8.3 (±0.6) g/dL pre-treatment initiation and 8.1 (±0.7) g/dL post-treatment initiation (Figure 2A). For those treated for over 365 days, the mean rate of VOCs per year was 2.2 (±2.7) (Figure 2B). 56% of patients had been admitted to the hospital at least once since starting treatment, primarily due to VOCs (56%) (Figure 2C). 78% of patients received blood transfusions, 11% of whom received regular transfusions. The most common transfusion interval was every 6–8 weeks (33%). Following Crizanlizumab treatment, the mean number of transfusions received over 12 months decreased from 4.7 to 2.8.

Summary/Conclusions: This work identified insights into the real-world impact of novel therapies, demonstrating their potential to enhance disease management and patient experience. Our analysis showed several improvements following post-treatment initiation: increased haemoglobin levels with Voxelotor treatment, reduced VOC frequency and hospital admission rates with Crizanlizumab treatment, in addition to lower transfusion rates for patients receiving both therapies. This highlights the significance of patient-reported experiences in helping healthcare providers tailor targeted treatment strategies, address the unmet needs of SCD patients, and better understand the patient perspective with novel therapeutic options for better overall health outcomes. Future research will focus on expanding the patient cohort to validate these findings and ensure translatable, representative findings.

1. Darbari et al. The European Journal of Haematology, 2020; 105, 237–246.

2. Migotsky et al. Pharmacy (Basel, Switzerland), 2022; 10(5), 123.

3. Chou et al. Blood Advances, 2020; 4(2), 327–355.

Topic: 002–Novel therapies, gene therapies, bone marrow transplant and emerging diagnostics

A. Rifai¹, D. Bukini¹, C. Kanza¹, J. Mashaka¹, E.P. Kisali¹, D. Maingu¹, F. Luoga¹, S. Karim¹, M.Z. Alimohamed¹, A.S. Said², H. Chuwa³, S. Konteh³, W. Lema³, M. Mohamed³, F. Konteh³, B. Temba³, A. Mongi ³, I.K. Minja¹, E. Balandya¹, F. Urio¹, G. Moshi⁴, J. Makani¹

Muhimbili University of Health and Allied Sciences¹, Sickle Cell Patients Community of Tanzania², Aga Khan Hospital³, KK Women's and Children's Hospital⁴

There has been considerable progress made to improve healthcare for sickle cell disease (SCD) in Africa. However, there are gaps in activities to provide advanced healthcare for SCD. Tanzania is the 4th country globally with the highest burden of SCD (birth prevalence of 8 per 1000 live births) with birth estimates of 15,000 annually, and a population prevalence of 200,000 people with SCD. Tanzania established one of the largest single-centre SCD programmes in the world and has developed an advanced therapy program for SCD (SickleARx) that includes Exchange Blood Transfusion (ExBT), Haematopoietic stem cell transplantation (HSCT) and Gene Therapy (GT) for SCD. This is a report on progress to establish the SickleARx program prioritizing five areas: Healthcare, Research, Advocacy including Patient Engagement, Training, Coordination including Partnership. PROGRESS: Advocacy (Patient Engagement): (i) SickleARx patient engagement camps were conducted (March–June 2021), for 50 patients and caregivers. (ii) Patient focused workshop was done on 11 June 2022 and 29th of April 2023, with 103 patients, caregivers and healthcare providers. Clinical Preparedness (i) A SickleARx registry was established by screening 1500 patients (September 2021 to May 2024) and identifying 157 patients (11%). (ii) 22 patients received ExBT (March 2021 - December 2023) with three cycles per patient; every four to six weeks. (iii) HLA Typing was done to establish a registry of SCD patients (recipients) and their families as potential HSCT donors: 33% out of 15 families had matched sibling donors. Gene therapy Research exploration: (i) the establishment of procedures for umbilical cord blood collection and registry for HSCT. (ii) The development of Target Product Profile (TPP) for both in vivo and ex vivo GT products to guide researchers, clinicians, and patients to agree on acceptable target endpoints that will define GT pathways at minimal and optimal conditions (iii) Potential factors that would influence in vivo GT was investigated by expert review and qualitative research with specific attention to the ethical, legal, and social issues. Training: Training and Education was provided through workshops, seminars, short courses, and the establishment of medium to long-term courses leading to postgraduate degrees. Partnerships: Networks and collaborations were established at different levels at National, Regional and Global levels to facilitation implementation of the program. Conclusion: Tanzania has made progress in establishing ARx for SCD, identifying areas to leverage and opportunities that require strengthening and development in order to find suitable, appropriate and cost-effective treatment and curative options for SCD in Africa.

Topic: 002–Novel therapies, gene therapies, bone marrow transplant and emerging diagnostics

K.G. Goldsborough¹, I.A. Almeida¹, J.P. Paderi², V.A.S. Sheehan¹

Emory University School of Medicine¹, IHP Therapeutics²

Background: Sickle cell disease (SCD) is a red cell disorder that affects more than 100,000 people in the US; over 200 children in Atlanta are affected. An abnormal hemoglobin, HbS, polymerizes under hypoxia, causing vaso-occlusion, ischemia, and acute severe pain events. The trigger for these pain events is often white blood cell adhesion via P-selectin to the blood vessel lining. The sickle red cell then adheres to the white cell; oxygen then dissociates from HbS, potentiating polymerization. With polymerization, the red cell becomes more rigid, and obstructs the microvasculature, blocking blood flow and oxygen. Without oxygen, tisue ischemia ensues, resulting in pain.

Aims: We propose to prevent painful vaso-occlusive events (VOE) by reducing the inciting event of white cell adhesion via P-selectin to the blood vessel via IHP-102, a novel glycan-based therapeutic that blocks P-selectin.

Methods: Acute dose-response studies of IHP-102 were conducted in Townes SS (SCD) and AA (control) mice. Both male and female mice (8 weeks old) were used to explore potential sex-related effects. Acute VOE was induced by hypoxia exposure (3 h at 10% O₂, 1 h reoxygenation, 2% O₂), and IHP-102 (0, 3, 10, 30 mg/kg, subcutaneous, SC) was administered 30 minutes before hypoxia. Behavioral (pain) testing for mechanical and thermal (hot & cold) hypersensitivity, as well as grip strength was performed 2–3 h post-injection/exposure.

Results: HbSS mice given saline and subjected to hypoxia had significantly increased sensitivity to cold compared to HbSS mice treated with IHP-102 and then subjected to hypoxia.

Discussion: Since we found a significant reduction in pain behaviors with administration of IHP prior to triggering VOE with hypoxia in the sickle mouse model, the analogous strategy in individuals with SCD would be administration of IHP-102 prior to onset of VOE. This requires awareness of impending or likely VOE, either through recognition of prodromal symptoms, of situations that typically trigger VOE in the individual, or wearbels that detect vital sign changes consistent with a VOE prodrome. Further modeling of IHP-102 in the SCD mouse model will determine if IHP-102 can impact pain behaviors if administered after the hypoxia insult. Conceptually, IHP is a game changing medication. Current home treatment for VOE are non-specific anti-inflammatory medication and opioids. IHP-102 could be administered SC by individuals with SCD in their home, preventing adhesion and vaso-occlusion in a targeted manner, reducing pain, opioid exposure, and need for hospitalization.

1. SK Ballas et al. Blood, 2012, 3647–3656.

2. MF Bennewitz et al. Blood Advances, 2020; 4.2, 266–273.

Topic: 002–Novel therapies, gene therapies, bone marrow transplant and emerging diagnostics

S.M.R. Felemban¹, A.S. Abdulhamid¹, A. Alghamdi¹, S.H. Nagro¹, R. Alessawi¹, N. Alamri¹, T.A. Alshuaibi¹

MOH-KING FAHD Hospital¹

Background: Beta Thalassemia is a congenital blood disease resulted from a defect in beta globin gene leading to alpha/beta globin chain imbalance which manifested with a wide range of hemolytic anemia, erythroid hyperplasia, transfusion requirement and iron overload. In TDT, the treatment includes red blood transfusion every 3–4 weeks, iron chelation and management of complications. Luspatercept (Reblozyle) is a recently approved medication which is a recombinant protein that binds to TGF-beta superfamily ligands and inhibits Smad2/3 signaling that is abnormally high in thalassemia patients resulting in erythroid maturation through differentiation of late-stage erythroid precursors in the bone marrow. this will promote erythroid precursor differentiation and improves ineffective erythropoiesis and anemia in thalassemia patients.⁸ The medication was approved by the European Medicines Agency (EMA) and and United States Food and Drug Administration (FDA) the approval was based on BELIEVE trial (NCT02604433), which concluded that luspatercept was associated with an improved of overall quality of life and a reduction in the regular blood transfusion required in patients with thalassemia with acceptable safety profile.^9,10 However, there was a recent multiple reported cases of patient on luspatercept who developed paravertebral region extramedullary hematopoiesis resulting in bilateral lower limbs weakness and in extreme cases Cauda equina syndrome.^11,12

Extramedullary hematopoiesis is one of the complications of thalassemia defined as the production of two or more hematopoietic lineages (myeloid, erythroid, and megakaryocytic cells) outside the bone marrow.¹³ It is commonly seen in the liver, spleen, lymph nodes, paraspinal/paravertebral region, and other areas of the body.¹³ It is more common in non-transfusion dependent thalassemia, in paraspinal extramedullary hematopoiesis patients may experience back pain, bilateral lower weakness, urinary and fecal incontinence, and saddle paresthesia due to spine compression.¹⁴ The management Often include intense blood transfusions program every two week with a goal of hemoglobin of 11.5, surgical approach (ect.laminectomy), radiotherapy, and medical approach which include steroids and hydroxyurea.^15–17

Case Summary: We reported a 36-year-old female patient a case of debilitating cauda equina syndrome whose suspected cause was the action of the recently approved agent Luspatercept. She started on Luspatercept 7 months prior to her symptoms, at 1 mg/kg which was increased by the third dose to 1.25 mg/kg due to poor initial response in Hb and SF levels. She presents with progressive constipation, intermittent urinary retention, and inability to walk. On examination, she was conscious alert and oriented. neurologically she exhibited intact bilateral upper limb power, but her lower limb power was measured at 3 out of 5 on both sides with decreased sensation un the para-anal area was observed. However, no other sensory deficit was noted. Her Hb was 8–10 mg/dL and SF 7316. Her MRI showed a large, well-defined-presacral multiloculated soft tissue mass arising from the anterior aspect of upper sacrum bone, measuring about 5 × 3.4 × 4.7 cm in transverse, anteroposterior and cranio-caudad dimension respectively. A smaller lobulated mass was also observed anterior to the lower sacrum, measuring 3.6 × 3.2 × 1.2 cm. Additionally, an oval-shaped lesion was seen posterior to S3 and S4, extending to the left side, measuring 0.8 × 1.5 × 2.5 cm. The MRI findings are most likely in keeping with extramedullary hematopoiesis with extension to the sacral foramen. Patient had her Luspatercept discontinued at the 7th dose, and she responded slowly to the hyper-transfusion program every 1–2 weeks to keep Hb above 11.5. Her symptoms progressively improved over a period of 8–16 weeks as she was able to walk normally and resuming a better control to her bowel movement and urine excretion.

Topic: 002–Novel therapies, gene therapies, bone marrow transplant and emerging diagnostics

M. Yassin¹, M. Cappellini², N. Shah³, C. Minniti⁴, S. AlKindi⁵, A. Al Zayed⁶, J. Altooq⁷, M. Qari⁸, M. Al-Rasheed⁹, N. Steitieh¹⁰, N. Sabra¹⁰

National Center for Cancer Care and Research¹, University of Milan², Duke University Medical Center³, Montefiore Medical Center, Albert Einstein College of Medicine⁴, Sultan Qaboos University Hospital⁵, Prince Mohammed Bin Fahad Hospital⁶, Hereditary Blood Disorder Center⁷, King Abdulaziz University Hospital⁸, Adan Hospital⁹, Pfizer¹⁰

Background: Sickle cell disease (SCD) is a genetic hemoglobin (Hb) disorder characterized by hemolytic anemia, painful vaso-occlusive (VOC) events, end-organ damage, and reduced life expectancy. For almost two decades, hydroxyurea remained the only disease-modifying drug prescribed in the management of SCD. However, currently, there is a dawn of new era of novel therapies with FDA approval of drugs such as L-glutamine (2017), crizanlizumab (2019), and voxelotor (2019) each targeting key elements of contributors to SCD pathophysiology. However, the European Medicines Agency, withdrew the marketing authorization for crizanlizumab in the European Union, in August 2023.

Aim: The objective of the current paper is to summarize the clinical outcomes of novel agents (L-glutamine, crizanlizumab and voxelotor) in the treatment of SCD, from clinical trials and real-world data, through a systematic literature review approach, to identify any gaps in the observations between the clinical trials and real-world studies and to highlight unmet needs requiring further research.

Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The study included all clinical trials, observational studies, case series and case reports published in English exploring the clinical outcomes of L-glutamine, crizanlizumab, and voxeletor, up to May 31, 2024. Studies published in non-English languages and study types such as trial protocols, ongoing trials without interim results, trials without results, narrative reviews, news, comments, notes, and animal studies were excluded. For quality and risk of bias assessment, the Cochrane Collaboration tool was used for the randomized controlled trials (RCT), the New Castle Ottawa (NOS) scale for observational studies, and the JBI (Joanna Briggs Institute) critical appraisal checklist for case reports.

Results: Of the total 812 articles, 97 articles met the inclusion criteria; 9 studies had L-glutamine as an intervention (3 were clinical trials, and 6 were real-world studies), 31 had crizanlizumab as an intervention (7 were case reports, 11 were real-world studies, and 13 were clinical trials), and 57 had voxelotor as an intervention (20 were clinical trials, 31 were real-world studies, and 6 were case reports).

A pivotal phase III study of L-glutamine (n = 230; 5–58 years of age) showed that patients treated with L-glutamine had a 25% reduction in pain crisis, 33% fewer hospital days compared to placebo and was generally well-tolerated with minimal side effects. However, real-world studies highlighted barrier to accessibility to the drug and patient adherence as major issues observed in clinical practice with the prescription of L-glutamine. In the SUSTAIN study (n = 198; 16–65 years of age), 5mg/kg dose of crizanlizumab reduced the occurrence of VOCs and hospitalizations by 45% and 41%, respectively, as well as reduced incidence of uncomplicated crisis (defined as crises other than the acute chest syndrome [ACS], hepatic sequestration, splenic sequestration, or priapism) by 62%. Furthermore, it extended the median duration before the first and second VOC. However, in the Phase III STAND study (n = 252, aged ≥12 years), no statistically significant differences in annualized rates of VOC and hospitalization, were observed between crizanlizumab (5 and 7.5 mg/kg) and placebo. Besides the clinical outcomes reported in the trials, real-world studies of crizanlizumab also showed a reduction in complicated VOC events, including ACS and priapism. Post-marketing reports of crizanlizumab have reported infusion-related reactions presenting as pain events in patients (n = 28) during and after crizanlizumab infusion. The HOPE (n = 274; 12–65 years) trial demonstrated a 51% improvement in hemoglobin response and a marked reduction in hemolysis markers in patients treated with voxelotor. However, real-world studies demonstrated additional clinical benefits not initially observed in pivotal clinical trials, which included reduction in VOC episodes, fewer hospital days, reduced need for blood transfusion, and improvement in renal function in patients treated with voxelotor. Profiles of the novel therapies for complications of SCD, based on the findings from this systemic review, has been delineated in Table below. In the table, impact of novel therapies on complications is provided based on evidence (Yes: data available from studies; No: Data not available from studies; Possible: scanty data).

Conclusion: According to the systematic review, the three novel therapies have substantial clinical benefits with tolerable safety profiles. However, currently, there is a lack of data on the effect of these novel therapies on end-organ specific complications of SCD and patient characteristics that influence selection of appropriate medication. Consequently, additional research is imperative to address these and further unresolved queries.

1. E Vichinsky et al. The New England Journal of Medicine, 2019; 381(6), 509–519.

2. KI Ataga et al. The New England Journal of Medicine, 2017; 376(5), 429–439.

3. MR Abboud et al. Blood, 2023; 142(1), 272.

4. E Vichinsky et al. The New England Journal of Medicine, 2019; 381(6), 509–519.

Topic: 002–Novel therapies, gene therapies, bone marrow transplant and emerging diagnostics

R. Mashingaidze-Mano¹, P. Kuona², J.M. Misihairabgwi³

University of Namibia Faculty of Health Sciences & Veterinary Medicine, School of Medicine, Department of Maternal & Child He¹, University of Zimbabwe, Faculty of Medicine and Health Sciences, Department of Child, Adolescent and Women's Health, Harare,² University of Namibia Faculty of Health Sciences & Veterinary Medicine, School of Medicine, Department of Human, Biological a³

Background: Sickle cell disease (SCD), a noncommunicable disease, has the greatest burden in sub-Saharan Africa. The majority of children (50%–90%) with SCD die before their 5th birthday, with approximately 150,000–300,000 annual SCD child deaths in Africa. In developed countries, newborn screening (NBS) has been shown to improve the survival of children with sickle cell disease, with under-5 childhood mortality reduced 10-fold due to interventions performed before the development of complications. Point-of-care tests have been developed for resource-limited settings to expand NBS. This study aimed to determine the birth prevalence of sickle cell disease in Namibia using the HemoTypeSCTM point-of-care test.

Methods: A cross-sectional descriptive study was carried out at four sites in three regions of Namibia. Four hundred and seventy-nine well newborns within 72 h of birth were recruited for the study from 21 February to the 16th July 2023. Descriptive statistics were used to compute the haemoglobin types of the study participants.

Results: The majority of the participants (n = 253; 52.8%) were females, and (n = 226; 47.2%) were males. The median age of the participants was 23 h (Q1, Q3; 13; 34),) with an age range of 2–98 h. Sickle cell trait was present in 5.2% of the screened newborns, no homozygous disease was detected, and 94.8% had Hb AA.

Conclusions: This study is the first to measure of HbS gene carriage at birth using HemotypeSC point-of-care testing in Namibia. There was a moderate prevalence of sickle cell traits but no SCD. This baseline study may provide the foundation for larger epidemiological surveys to map HbS gene carriage in Namibia to provide evidence for policymakers to fashion appropriate SCD newborn screening services.

Topic: 002–Novel therapies, gene therapies, bone marrow transplant and emerging diagnostics

J.S.K. Shakilu¹, D.M.M. Mashala¹, L.W.K. Lyodd¹, U.C.R. Uderzo², F.G.R. Gilgio², A.P.M. Patrick¹, Z.K.Z. Zimbwe¹, S.W.M. Malangahe¹

Benjamin Mkapa Hospital¹, Help3 Onlus²

Background: At present, hematopoietic stem cell transplant is the only cost effective and feasible curative intervention for most of hematological diseases like sickle cell disease. There is an obvious gap in terms of accessibility of this service to African countries, considering huge burden of this disease, where almost 75% of global SCD births are found. Tanzania, with almost 14,000 annual SCD births, has made efforts to establish the first center in East African region which offers the service to SCD, with ongoing future plans of expanding the service to other hematological conditions.

Methods: From 2018, Benjamin Mkapa Hospital in collaboration with an Italian NGO (Help3), set a common goal to establish the 1st HSCT for SCD in the region. With the support of the Association HELP3-ODV (Monza, Italy, www.help3.it), starting from 2019 a series of videoconference lectures were done by international HSCT experts to train Tanzanian health professionals. Four nurses, two doctors and two laboratory scientists took part in an observational internship in Italy at different HSCT Centers. Renovation of the preexisting normal ward to meet the ward standards of HSCT ward was done simultaneously with upgrading of the pharmacy, laboratory services and blood bank which are crucial components for HSCT services. In January 2023 HSCT program started at BMH with the presence of experienced Italian staff in Tanzania for the first 4 months. Weekly online clinical and logistical round started in March 2023 and are ongoing. Conditioning regimen consisted of Busulfan, Rabbit Antithymocyte Globulin (ATG) and Cyclophosphamide. Prophylaxis of graft versus host disease (GVHD) consisted of methotrexate and cyclosporine. Standard Levetiracetam and antimicrobial prophylaxis were used. Early in 2023, all patients with symptomatic SCD, received bone marrow stem cells harvested from HLA-identical siblings.

Results: From January to May 2024 9 HSCT were performed, two females and 7 males. The median age was 7 (range 4–11). Median TNC infused was 5.7 × 10⁸/kg of patient BW (range 4.7–8.9).

Conditioning regimen was well tolerated without grade III–IV adverse events. All patients engrafted with a median ANC and PLT engraftment at day + 27 (range 19–41) and at day + 25 (range 15–35), respectively.

All patients experienced febrile neutropenia, responding to broad-spectrum antibiotics. Microbiological findings on blood cultures were P. Falciparum, Coagulase-negative Staphylococci, and Gram positive rods, all resolved.

Grade II Skin aGVHD was diagnosed on day +21 in one patient, treated with Prednisolone alone obtaining complete resolution. At a median follow-up of +309 (range 196–315) from HSCT, no other GVHD were diagnosed. One patient was diagnosed with oral HPV lesions, now receiving treatment. No other long-term complications were diagnosed.

All patients remain transfusion free, without SCD events after HSCT with blood counts and HbS levels compatible with complete engraftment and complete chimerism.

Conclusion: First 9 allogeneic HSCT performed in Tanzania.

HSCT is feasible in LMICs without major adjustments on infrastructures and human resources.

• The first 8 patients are now asymptomatic with full chimerism.

• The first 4 patients stopped IS.

• The first 3 patients are back to school.

4 Patients have been transplanted without the Italian staff at BMH.

Weekly online clinical-logistical round started in March 2023 and are ongoing.

Supply chain of drugs and consumables remain a major issue.

Future Plans

• Tanzanian government has promised to support BMT at BMH Hospital.

• It is fundamental to ensure sustainability of the service considering the immense need of HSCT.

• Maintaining the cost affordable and creating a reliable supply chain of drugs and consumables will be crucial.

• An ad hoc analysis in ongoing to evaluate the cost-effectiveness of HSCT at BMH, comparing HSCT cost to standard of care of SCD patients (considering direct/indirect costs).

• Continuous training for health professionals is ongoing and needs to be implemented.

• Expand HSCT to ABO mismatch host/donor.

• Expand HSCT to other disordes.

• Collaborate with other Tanzanian Hospital to create a BMT Network.

Topic: 002–Novel therapies, gene therapies, bone marrow transplant and emerging diagnostics

M.N. Nurudeen¹, I.F. Oyelade², B.S. Bolarinwa²

Kwara State University Malete¹, Haima Health Initiative²

Background: The burden of sickle cell disease (SCD) in Nigeria is the largest in the world, with limited treatment options over the last few decades despite significant medical advancements for other diseases. The introduction of hydroxyurea for the management of SCD remained the only new treatment available for several years, given the significant limitations of bone marrow transplants in Nigeria. Fortunately, advancement in research has resulted in new management and treatment options such as oxbryta/voxelotor, crizanlizumab and gene therapy. Despite the excitement for these developments, knowledge and perception about these treatment modalities remain poorly understood amongst patients and their families, especially outside of the US and Europe where most patients live.

Aims: This study aims to understand the awareness and attitudes of SCD patients and their carers of emerging and novel SCD therapies in Nigeria, identify their perceived barriers to access, and collate useful recommendations for researchers and practitioners to improve communication, research and adoption of new therapies.

Method: A cross-sectional study was performed through the use of electronically transmitted surveys to 183 respondents in Nigeria. The survey respondents were individuals aged 18 years and above with SCD or a family member with SCD. Quantitative data such as demographics, (age group, sex, genotype), knowledge about treatments, interest in acquiring knowledge about the therapies and using them if recommended, barriers to accessing the therapies, concerns about the disease-modifying therapies, and patients' expectations were collated and analysed.

Results: About 75% of the respondents were females and 25% were males. Approximately 80% have HbSS or live with someone who has the HbSS genotype while the remaining 20% are HbSC. 77% and 67% of the respondents are familiar with bone marrow transplant and hydroxyurea respectively; 30% are familiar with gene therapy while only 17% of the respondents have heard of oxbryta/voxelotor and crizanlizumab. Most respondents depend on healthcare professionals and patient advocacy groups to stay current on the available treatment options. The lack of adequate knowledge about these new therapies has limited their hopes for effective treatment, improved quality of life and survival. In addition, the high cost of the therapies, limited access, inadequate medical infrastructure and concerns about adverse effects will limit the adoption of effective new therapeutic interventions including the use of hydroxyurea and bone marrow transplants. For most respondents, there was a larger interest in improving SCD complications such as pain, leg ulcers and organ damage over curative therapies. Despite these barriers, 96% of respondents want to stay up-to-date on the latest breakthroughs in SCD treatment or management even if they are unavailable in Nigeria, as these advances offer a beacon of hope for people living with SCD and their families.

Conclusion: From the responses obtained, Nigerian SCD patients and carers feel like their hopes for better clinical treatments are limited by a lack of information and uncertainties in the aftermath of some of the known therapy options. Our study shows that the majority of respondents are unaware of the recent advances in SCD therapy but would love to be informed. Hence, it is important to strengthen the dissemination of information about new therapies to promote awareness and improve the accessibility of Nigerians to these novel therapeutic options. This should be done by the media, community support groups and healthcare providers, where most patients get their information from.

1. Lugthart et al. Expert Opinion on Pharmacotherapy, 2024; 25(2), 157–170.

2. Matte et al. Mediterranean Journal of Hematology and Infectious Diseases, 2019; 11, 1.

3. Nnagha et al. Annals of Medicine and Surgery, 2023; 85(5), 2282–2286.

Topic: 002–Novel therapies, gene therapies, bone marrow transplant and emerging diagnostics

A.G. Guindo¹, B.A.T. Toure¹, A.I. Koya¹, I.K. Keita¹, M.C. Coulibaly¹, O.T. Tessougue¹, I.C. Cisse¹

Center de Recherche et de Lutte contre la Drepanocytose¹

Background: SCD primarily affects people in sub-Saharan Africa, caused by a point mutation in the beta globin gene that leads to the formation of banana-shaped red blood cells in low-oxygen environments. It is inherited from both AS trait parents. Inadequate diagnostic resources, such as high-tech devices and financial constraints, contribute to the majority of children with SCD in Africa dying before their 5th birthday. We propose that dried blood spot (DBS) and point-of-care test (POCT) can improve early diagnosis and accuracy in low-resource settings.

Objective: Comparing DBS and POCT in diagnosing SCD in a low-resource context.

Methods: Six individuals from a rural healthcare center comprising 2 midwives, 2 nurses, a laboratory technician, and a laboratory scientist were trained on how to take a heal prick test for DBS (HemoTypeSC trademark)and POCT. The results of 100 babies were sent by post to the CRLD, where they were analyzed.

Results: DBS shows high specificity in detecting SS, AS, and AC (100%, 100%, and 99% respectively). DBS was highly sensitive (100%) in detecting hemoglobin AA phenotype. POCT was found to have 100% sensitivity and specificity for sickle cell trait (AS), with variable results for other phenotypes.

Conclusion: Our study shows that DBS can be used as a confirmatory test in a low-resource setting for SCD. It also shows that POCT can be used to screen SCT which can be very helpful in educating people early in life on SCD inheritance patterns.

1. Ma et al. Gene, 2023, 147480.

Topic: 002–Novel therapies, gene therapies, bone marrow transplant and emerging diagnostics

M. Mhozya¹, S. Malangahe¹, A. Orsini², B. Mbuba¹, D. Lyimo¹, P.E. Ronchi², S. Temba¹, H. Sumari¹, F. Francis¹, C. Tassi³, G.B. Ceccherelli⁴, J. Shakilu¹, M.M. Katura⁵, A. Chandika¹, C. Uderzo⁶

BMH¹, IRCCS San Raffaele², Help3 OVD³, Azienda Ospedaliera Policlinico di Modena⁴, Central zone blood Transfusion CenteR⁵, Help3 ODV⁶

Background: The SCD prevalence in Sub Saharan region is the highest in the world; high under-5 mortality rate (50%–90%) and poor quality of life require highly effective diagnostic and therapeutic programmes. Currently, allogeneic BMT is the only feasible curative treatment in LMICs, but affordable and sustainable only in few centres so far. In 2019, the BMH in Dodoma, as first hospital in Tanzania, launched a paediatric BMT project in partnership with two Italian University Hospitals (San Gerardo in Monza and San Raffaele in Milan) with the support of the Help3 NGO. Since then, the BMH Haematology Unit and the Damu Salama Transfusion Centre have been cooperating to the successful course of transplantation. Since 2020, the Transfusion Centre started a global upgrade to support the project.

Aims: First, to describe the improvement of BMH's Transfusion Centre necessary to support the development of the BMT programme, by taking into account the stringent requirements of feasibility and sustainability; second, to present a few preliminary data concerning the first 10 consecutive allotransplanted SCD patients.

Methods: Damu Salama: In 2020, the Transfusion Centre relocated in a new building, where blood collection, separation and processing are performed, except blood units' validation. From 2023 irradiated PRCs and platelet units are distributed and automated Erythro-Exchange (EEX) procedures are performed. Moreover, in selected cases of a-GVHD, off-line ECP can be carried out. A Quality Management system is being implemented according to National Blood Transfusion Service's standards. Two laboratory technicians have been trained in an Italian centre (Azienda Ospedaliera Universitaria, Policlinico di Modena) and other educational activities have been performed onsite by Italian specialists.

Haematology Laboratory: At present, ABO-Rh blood grouping, pre-transfusion tests, crossmatches and pathological haemoglobin detection are performed in the Haematology Laboratory, while second level immuno-haematological tests are managed in outsourcing.

Donors and Patients: Since January 2023, SCD patients submitted to BMT have received the Bone Marrow from HLA identical sibling. 1 or 2 EEXs and /or a top-up transfusion are carried out before the conditioning regimen, in BM recipients. The transfusion centre has in charge overall transfusion support, as well pre-explant auto donations and donation eligibility exams in BM donors.

Results: Until May 2024, 9 BMTs have been carried out without major adverse events or reactions with a mean follow up of 231 days and in absence of significant GVHD, relapse or major complications. Figure 1 summarises donor and patient data according the donor's haemoglobin profile, namely AS carrier or AA normal.

Summary and conclusion: Preliminary results seem to confirm that allogeneic BMT is feasible in Tanzania, as all patients recovered their bone marrow functions and well tolerated any SCD related treatment. However, unexpected delays in the supply of reagents and devices have significantly impaired the activities, thus logistic improvements are mandatory to guarantee a continuous optimal treatment for patients and obtain national and international accreditations. In spite of these and other difficulties, thanks to the Hospital General Management, the personnel commitment, the consistent support from the Central Zone Blood Bank and the partnership with Italian experts, the prospects of success of the BMT programme are encouraging.

1. Brandow et al. Journal of Hematology & Oncology, 2022; 15, 20.

2. Mtenga et al. British Journal of Haematology, 2021;192(1):17:20.

3. Makani et al. Hematology/Oncology and Stem Cell Therapy, 2020; 66, 70.

Topic: 002–Novel therapies, gene therapies, bone marrow transplant and emerging diagnostics

J.C. Fan-Hsu¹, L.L.H. Hsu²

Judy Fan-Hsu, D.D.S.¹, University of Illinois at Chicago²

Introduction: Oral mucositis and salivary dryness are expected when high-dose chemotherapy is used for cell and gene therapy, and pre-existing infections of teeth or gums can make oral mucositis more severe and costly, even if mortality might be only 0.2% higher (Uutela, 2019). New waves of individuals with sickle cell disease (SCD) will enter the complex journeys of gene therapies because of the 2023 approval of Lygenia and Casgevy in several countries. A landmark international consensus (Elad, 2015) and National Institutes of Dental Craniofacial Research guidelines entitled “Dental management of the organ or stem cell transplant patient” are applied to other high-dose chemotherapy such as gene therapy procedures for SCD. Recently, several publications examined oral health in SCD. Dental problems in SCD include aseptic pulpal necrosis (sterile inflammation), low bone density in the jaws, and malocclusion. Evidence is mixed about whether SCD affects enamel mineralization. Earlier studies speculated that caries prevalence might be higher in SCD, but subsequent studies suggest low dental utilization is a major contributor. Antibiotic prophylaxis against Streptococcus pneumoniae might protect against dental decay. This study sought to gather evidence to inform dental care for individuals with SCD in the process of gene therapy.

Methods: A scoping review of literature from January 2016 to May 2024 in PubMed, Cochrane Review, EMBASE, CINAHL, SCOPUS, Trip Pro, and SCIELO used keywords [sickle cell disease, oral management, dental management, oral health, mucositis, caries, hematopoietic stem cell transplant, gene therapy]. SCIELO was selected because it is known to be rich in Brazilian dental research publications. Oral graft-versus-host disease was excluded as not relevant to gene therapy.

Results: The scoping review found 48 papers, with no clinical trials that specifically examined dental care for individuals with SCD in the process of cell and gene therapies or afterwards, other than oral manifestations of Graft-versus-Host disease. The NIDCR 2016 guideline has been updated with a 3-part expert consensus (Correa, 2023; Gobbi, 2023; Santos, 2023). Clinical trials on oral management in hematopoietic stem cell transplantation (HSCT) did not report on SCD (Skallsjo 2023, Guberti 2022). Benzinelli and colleagues (2021) showed that a laser protocol to remove oral infection before chemotherapy resulted in less severe oral mucositis, shorter hospital stays, and lower costs, but did not report on SCD.

Conclusion: Only indirect evidence guides dental care for individuals with SCD in the process of gene therapies or afterwards. However, oral health management for SCD will probably be adapted from other bone marrow transplants and from high-dose chemotherapy until there is disease-specific data.

SUGGESTED REGIMEN FOR SCD GENE THERAPY: (baseline) I maintain good oral health with brushing, flossing, and regular visits to the dentist, (1) see a dentist early before the gene therapy process to allow enough time for dental preparation. (2) get oral infections treated at least 10 days prior to high-dose chemotherapy for SCD gene therapy. (3) if there is no time for healing before high-dose chemotherapy, consider using laser therapy to reduce the risk of infectious foci causing complications during gene therapy. (4) use chlorhexidine rinse and other measures to reduce oral mucositis. (5) if salivary dryness occurs, add fluoride therapy.

Topic: 003–Clinical and epidemiological studies

A. Anushka¹, K.N. Saraswathy¹

University of Delhi¹

Background: India's resident population is multi-regional and multi-cultural. This ethnically diverse population is perfect for researching heritable diseases like hemoglobinopathy. Hemoglobinopathies are an array of disorders that affect hemoglobin (Hb) function. They are caused by either thalassemia or aberrant Hb. Thalassemia is induced by reduced globin chain synthesis, whereas a qualitative structural anomaly of the Hb molecule causes aberrant Hb. The structural hemoglobin variant known as hemoglobin E (HbE) is prevalent and is seen at high frequencies in several Asian countries. HbE is a common structural β-haemoglobin variant. Although HbE alone does not cause significant clinical problems, its interactions with other thalassemia produce syndromes of varying severity. While its coinheritance with β thalassemia, a condition known as hemoglobin E β thalassemia, is by far the most prevalent severe type of β thalassemia in Asia, its interactions with various forms of α thalassemia result in a wide variety of clinical problems. Many studies have been conducted to determine the prevalence of different hemoglobinopathies in the Indian population. The data on the prevalence of HbE traits with different socio-demographic variables is scarce.

Aim: to determine the prevalence and distribution of HbE trait among young adults in Delhi NCR, India.

Methods: The present study is a cross-sectional study in which total of 3481 young adults aged 18–35 years were recruited. In our study, participants from different states of India were undertaken for screening along with varied socio-demographic variables. Participants were divided according to six zonal councils of India from where they belong. 5 mL of blood was taken in EDTA-coated vacutainers. RBC indices were measured on an automated hematology analyzer while the percentage of HbA2 and HbF were estimated by Variant II High-Performance Liquid Chromatography machine.

Results: The overall prevalence of the HbE trait was 0.5%. As an expected pattern of distribution from previous studies, the distribution of HbE was found to be significantly higher among individuals from North-Eastern regions (10.3%) compared to other zonal councils of India (p < 0.001).

Conclusion: There are few facilities available in many nations to control significant clinical disorders like thalassemia and aberrant hemoglobin conditions. Understanding and identifying, the uncommon Hb variations in different regions of India could aid in prenatal diagnosis, genetic counseling, clinical diagnosis, and treatment of affected individuals.

1. Sharma et al. Indian Journal of Hematology and Blood Transfusion, 2012; 21, 5.

2. Fucharoen et al. Cold Spring Harbor Perspectives in Medicine, 2012; 2(8)

3. Mohanty et al. Journal of Community Genetics, 2012; 4, 33.

4. Iyer et al. Clinica Chimica Acta, 2015; 444, 229.

5. Kishore et al. Hematology, 2007; 12(4), 343–347.

Topic: 003–Clinical and epidemiological studies

S. Suokhrie¹, N.K. Devi¹, K.N. Saraswathy¹

University of Delhi¹

Background: β-thalassemia is an inherited hemoglobin disorder characterized by impaired synthesis of the beta-globin chain, resulting in chronic hemolytic anemia. The carrier state of the beta-thalassemia trait, also known as heterozygous β-thalassemia or β-thalassemia minor (Tm), is a clinically silent condition typically asymptomatic with mild anemia. Previous studies suggest that β-thalassemia trait may be protective against cardiovascular adversities. Dyslipidemia and obesity are well-established risk factors for cardiovascular diseases, however, the presence of β-thalassemia trait could potentially have a protective effect. The heterozygous advantage of β-thalassemia trait in terms of dyslipidemia and obesity has not been extensively explored, particularly within the Indian population. The study aims to understand the possible protective effect of heterozygosity for β-thalassemia on the incidence of dyslipidemia and obesity in the study population.

Method: The present study is a cross-sectional study wherein 3500 college-going young adults between the age group of 18–35 years residing in Delhi and NCR region, India were screened. Anthropometric measurements were undertaken following a standardized protocol. After taking informed consent, 3 ml of blood was drawn and serum was separated for measuring serum TC, LDL, HDL, and TG. For determination of thalassemia carrier status complete blood count (CBC) and high-performance liquid chromatography (HPLC) were performed. The screening for beta-thalassemia carriers (HbA2 4–8, MCV ≤80, MCH ≤27) followed the guidelines of the Department of Health and Family Welfare, Govt of India. And 69 β-thalassemia carriers and 138 age-sex-matched controls were shortlisted for the study.

Result: Statistical analysis of serum lipid variables and obesity variables in β-thalassemia trait and control group revealed a significant difference in the distribution of serum HDL-C, wherein the prevalence of low HDL was higher among the cases. The prevalence of individuals with general obesity was significantly lower among those with β-thalassemia trait compared to the control group. However, other lipid and obesity variables did not show any significant difference. Further, odds ratio analysis revealed a 1.8-fold increased risk (OR 1.881, CI 1.022–3.463, p 0.041) for low HDL-C among the carriers. It was also observed that the β-thalassemia trait significantly played a protective role for obesity (OR 0.251, CI 0.095–0.665, p 0.005).

Conclusion: The study revealed that individuals with the β-thalassemia trait have an increased risk for low HDL-C, this underscores the importance of this index for the prognosis of future cardiac events among individuals with β-thalassemia trait. Interestingly, β-thalassemia trait also showed a protective effect against general obesity. However, the cause-and-effect relationship could not be ascertained due to the limited design of the study. Further research is necessary to investigate and understand the underlying mechanism of this association.

Topic: 003–Clinical and epidemiological studies

R.D. Deb¹

Amity University, Uttar Pradesh¹

Thalassemia is the most common monogenic disorder in the world with an autosomal recessive pattern of inheritance (Basu 2015; Shaikh et al., 2022), imposing a heavy economic burden on families and the nation. In severe forms, it is associated with chronic, life-impairing, and life-threatening diseases that can lead to disability or death. Unfortunately, many children worldwide continue to be born with and suffer from Beta Thalassemia due to a lack of awareness and comprehensive prevention programs. The incidence rate on the Southern Mediterranean coast is the highest, at 36.8 per 100,000 newborns (Bellis et al., 2021). Around 3%–10% of the Indonesian population carries beta-thalassemia (Wahidiyat et al., 2022). Thailand has a population of 66.2 million with 30.0%–40.0% of them carrying thalassemia genes (Paiboonsukwong et al., 2022). In many Asian countries including India, the frequency of β-thalassemia is closely intertwined with social, cultural, and religious issues of the respective country (Chawla, 2017). The current population of India has surpassed China and is equivalent to 17% of the global total and the genetic diversity of the Indian population, with large numbers of endogamous ethnic, geographical, religious and social groupings each with extended, unbroken genealogical histories, adds to the complexity of the prevalence and burden of genetic disorders, as observed in regional and caste-specific analyses of mutation data on hemoglobinopathies (Singh et al., 2021).

Beta thalassemia carrier status is a significant health concern in India, there are more than 40 million carriers of β-thalassemia (β-thal) in India with 10,000–12,000 affected births every year (Vachhani et al., 2022). The demographics of the Beta Thalassemia trait in India show significant regional and ethnic variation. The prevalence ranges from less than 1% to as high as 17%, with an average of about 3.3% in the general population. Specific regions such as Punjab and Tamil Nadu report the prevalence rate of Beta thalassemia to be approximately 6.5% and 8.4%, respectively. The trait is more commonly found in certain communities due to genetic factors and the high rate of consanguineous marriages, which increase the likelihood of inheriting the disorder (Thalassemia India). Keeping in view, with the above facts, the present study will review the distribution of thalassemia across the different regions and ethnic communities in India, focusing on the demographic and genetic aspects of this devastating hereditary disorder. The findings will help in targeted public health interventions and genetic counselling services to manage and reduce the burden of this disorder.

Topic: 003–Clinical and epidemiological studies

D.R. Pradyumna Kumar Dash¹, D.R. Sudha Sethy¹, D.R. Rabindra Kumar Jena¹

S.C.B Medical College and Hospital, Cuttack¹

Background: Sickle cell disease (SCD) belongs to hemoglobinopathies, where a single base pair change, thymine for adenine at 6th codon of beta globin gene results in HbS(Sickle hemoglobin). This change encodes for valine in place of glutamine at 6th residue in betaglobin molecule. Deoxygenation of HbS molecules results in long helical polymers formed through hydrophobic interactions, which in turn deform the red blood cell (RBC) into sickle shape. The sickled RBCs occlude microvascular circulation causing vascular damage, organ infarcts, painful crises and are prone for early hemolysis. Haplotypes, described as polymorphic restriction endonuclease sites in and around the mutant betaglobin gene are designated by geographic areas, they were first identified at. The Arab-Indian haplotype is usually found in persian gulf and India. Thus recurrent vasoocclusive crisis (VOC) and chronic hemolytic anemia are main clinical presentation and vary remarkably across various haplotypes. Phenotypic expression of SCD in India (Arab-Indian haplotype) is supposed to have different clinical presentation which has not been evaluated in large series in systemic way yet. The present observational study in single institution has been taken up to address this issue.

Aims: (1) To assess the phenotype: Only VOC type, only hemolytic type, and mixed type. (2) To study the transfusion requirement and iron overload status in SCD (homozygous) in Eastern Odisha. (3)To study the incidence of alloantibodies and its relation with blood transfusion.

Methods: This is a observational study conducted in Department of Clinical Hematology SCB MCH Cuttack, Odisha in between January 2024 to April 2024 with written informed consent. SCD (Homozygous) patients between 1 year to 70 years of age were included in the study. Severe comorbid and viral marker positive patients were excluded. Baseline charecterstics like age, sex. districts and clinical history like age of disease onset, age of first pain, age of first blood transfusion, total units of blood transfusion, rate/number of hospitalisation and painful crises were obtained. General examination and systemic examination was done. Evaluation of phenotypes: VOC type was analysed by obtaining the history of painful crisis, acute chest syndrome and dactylitis. Hemolytic type was diagnosed by unconjugated hyperbilirubinemia, anemia (hemoglobin <10 g/dL), splenomegaly, retic count (>2%), serum lactate dehydrogenase (>600 U/L), serum haptoglobin (<0.3 g/L) and mixed type had both the above features. The transfusion history was taken in form of total number of units of blood taken, frequency(occasional or regular-1 to 2 to units blood transfusion/month). Serum ferritin assay was done and correlated with different phenotypes and transfusion requirements. Allo-antibody test was done by indirect coombs test, antibody screening was done by 3 cell panel, antibody identification was done by 11/16 cell panel. At the end of the study we analysed baseline charecterstics, phenotypic presentation, correlation of serum ferritin with transfusion requirements and incidence of alloantibodies and its correlation with blood transfusion.

Result: Amongst 256 SCD patients enrolled, 23% were from Dhenkanal and 15% from Angul districts of Odisha. The median age was 20 (3–60) years and M:F ratio was 5:3. The clinical parameters observed: Pallor n = 218 (88.15%), Icterus n = 142 (55.46%), splenomegaly n = 117 (46%), presentation with acute painful crises n = 86 (33.59%), acute chest syndrome n = 45 (17.57%), limb pain n = 72 (28.12%), fever n = 32 (12.5%), avascular necrosis of femur n = 14 (5.46%), leg ulcer n = 2, Bell's palsy n = 1, gall stone n = 22 (8.5%), hospitalisation n = 72 (28.12%), fever, cough (history of infection during the diagnosis) n = 36 (14%), number of pain episodes per year 0–1 (3%), 1–2 (57.22%), 2–3 (29.11%), 3–4 (10.15%), 4–5 (9.37%), >5 (5.46%). Phenotypes observed: VOC only n = 92 (35.93%), hemolytic only n = 6 (2.34%), mixed type n = 158 (61.71%). Baseline charecterstics of laboratory parameters: median values: HbF: 20.850 (2.9–38.5), HbS: 70.7 (42.7–87.3), Hb (g/dL): 9.2 (4.4–14), MCV (fl): 80.5 (54.7–132), retic (%): 4.3 (0.3–20.59), ferritin (ng/mL): 275 (15–1800), LDH (U/L): 646 (164–3200), haptoglobin (g/L): 0.0250 (0.02–2.4), total bilirubin (mg/dL): 2.6 (0.8–12.6), indirect bilirubin (mg/dL): 1.7 (0.2–10), spleen size in cm: 0 cm (0–10). Total packed RBC in units; 1–10: n = 130, 11–29: n = 24, 30–49: n = 6.50–100: n = 8, 0: n = 88. Occasional transfusion seen: n = 160 (62.5%), regular transfusion: n = 8 (3.1%). The serum ferritin level >1000 ng/mL was maximum in 50–100 units group that is more with regular transfusions. The alloantibodies seen: n = 8 (3.125%) and all cases were occasionaly transfused. Auto immune hemolytic anemia seen in 5 cases.

Conclusion: In this study we found mixed type (both VOC and hemolytic) is the commonest phenotype followed by only VOC, only hemolytic type. Transfusion requirement was occasional in most of the cases (62.5%) and occurence of iron overload was less. Iron chelation was required in 6% of cases. Alloantibodies were found in 3% of cases at baseline.

Topic: 003–Clinical and epidemiological studies

K.H.M. Kuo¹, H. Al-Samkari², Y. Aydinok³, M. Besser⁴, A.N. Boscoe⁵, G. De Luna⁶, J.H. Estepp⁵, S. Gheuens⁵, K.S. Gilroy⁵, A. Glenthøj⁷, A.S. Goh⁸, A. Kattamis⁹, S.R. Loggetto¹⁰, S. Morris⁵, K.M. Musallam¹¹, K. Osman⁵, P. Ricchi¹², E. Salido-Fiérrez¹³, S. Sheth¹⁴, F. Tai⁵, K. Uhlig⁵, V. Viprakasit¹⁵, M.D. Cappellini¹⁶, A.T. Taher¹⁷

University of Toronto¹, Massachusetts General Hospital, Harvard Medical School², Ege University School of Medicine³, Cambridge University Hospitals NHS Foundation Trust⁴, Agios Pharmaceuticals, Inc.⁵, Hôpital Henri Mondor APHP⁶, Copenhagen University Hospital-Rigshospitalet⁷, Hospital Pulau Pinang⁸, National and Kapodistrian University of Athens⁹, São Paulo Blood Bank–GSH Group¹⁰, Burjeel Medical City¹¹, Azienda Ospedaliera di Rilievo¹², Hospital Clínico Universitario Virgen de la Arrixaca-IMIB¹³, Weill Cornell Medicine¹⁴, Siriraj Hospital, Mahidol University¹⁵, University of Milan, Ca' Granda Foundation IRCCS Maggiore Policlinico Hospital¹⁶, American University of Beirut Medical Center¹⁷

Background: Thalassemia, a group of inherited disorders characterized by ineffective erythropoiesis and chronic hemolytic anemia, is associated with wide-ranging impacts on health-related quality of life (HRQoL), such as impaired physical functioning and fatigue.¹ Anemia has been associated with increased symptom burden and poor HRQoL in patients (pts) with non–transfusion-dependent thalassemia (NTDT).^1,2 There are no available oral disease-modifying therapies that have been shown to improve HRQoL in β-thalassemia and no agents are approved for α-thalassemia.^3–6 In a phase 2 study of pts with NTDT, improvements in hemoglobin were observed with mitapivat, a first-in-class, oral, allosteric activator of pyruvate kinase, and it has the potential to improve HRQoL.⁷

Aims: To evaluate the impact of mitapivat vs placebo on fatigue, physical function, and other thalassemia symptoms in adults with α- or β-NTDT in ENERGIZE, a phase 3, double-blind, randomized, placebo-controlled, global trial.

Methods: Adults (≥18 years) were randomized 2:1 to mitapivat 100 mg twice daily or placebo for 24 weeks (wks) following informed consent (IC). NTDT was defined as ≤5 red blood cell (RBC) units transfused in the 24 wks before randomization and no RBC transfusions ≤8 wks before IC or during screening. The Functional Assessment of Chronic Illness Therapy–Fatigue Scale (FACIT-Fatigue), 6-minute walk test (6MWT), and Patient Global Impression of Change (PGIC) of Fatigue, Thalassemia Symptoms, and Walking Capacity were among the outcomes assessed. Changes from baseline (BL) for FACIT-Fatigue (Weeks 12–24) and 6MWT (Week 24), and the results of PGIC-Fatigue (Weeks 12–24), PGIC-Thalassemia Symptoms, and PGIC-Walking Capacity (both Week 24) were summarized. The clinically meaningful within-person change (MWPC) threshold for FACIT-Fatigue was estimated to be a ≥4.5-point change from BL in average score from Weeks 12–24, using an anchor-based method.

Results: 194 pts were randomized (mitapivat N = 130; placebo N = 64); BL characteristics were similar between treatment arms. Mitapivat demonstrated a statistically significant improvement compared with placebo in change from BL to Weeks 12–24 average FACIT-Fatigue score; least-squares mean (LSM) change from BL was 4.85 for mitapivat versus 1.46 for placebo (LSM difference (95% CI): 3.40 (1.21, 5.59); 2-sided p = 0.0026), and 36.2% of pts in the mitapivat arm achieved the MWPC threshold of ≥4.5 versus 21.9% in the placebo arm (Figure). For the 6MWT, LSM change from BL to Week 24 was 30.48 m for mitapivat and 7.11 m for placebo (LSM difference (95% CI): 23.36 m (6.90, 39.83)).

The observed frequency of pts with improvements (reporting feeling much/a little better) in PGIC-Fatigue was higher for pts in the mitapivat arm than the placebo arm at Week 12 (63.1% vs. 23.4%), Week 16 (69.2% vs. 23.4%), Week 20 (62.3% vs. 28.1%), and Week 24 (60.8% vs. 31.3%). Improvements in PGIC-Thalassemia Symptoms and PGIC-Walking Capacity were also reported in a higher frequency of pts in the mitapivat arm than in the placebo arm at Week 24 (67.7% vs. 32.8%; 55.4% vs. 28.1%, respectively).

Summary/Conclusion: Mitapivat is the first oral, disease-modifying, investigational therapy with which meaningful improvements in aspects of HRQoL, including fatigue and walking capacity, were observed in a clinical trial that enrolled both pts with α-NTDT and pts with β-NTDT.

1. Taher et al. In: Nicosia (Cyprus): Thalassaemia International Federation 3rd ed; 2023. www.ncbi.nlm.nih.gov/books/NBK599489/

2. Cappellini et al. The American Journal of Hematology, 2019; 94, E261–E264.

3. Amid et al. In: Nicosia (Cyprus): Thalassaemia International Federation 3rd ed; 2023. www.ncbi.nlm.nih.gov/books/NBK602223/

4. Harewood and Azevedo, In: Treasure Island (FL): StatPearls [Internet]; 2022. www.ncbi.nlm.nih.gov/books/NBK441826/

5. Langer, Esrick, Hematology American Society of Hematology Education Program, 2021; 2021, 600–606.

6. Taher et al. Expert Review of Hematology, 2021; 14, 897–909.

7. Kuo et al. Lancet, 2022; 400, 493–501.

Topic: 003–Clinical and epidemiological studies

C.D. Dinah¹, K.B. Balaskas², B. Greystoke³, R. Awadzi¹, P. Beke⁴, R. Ahern¹, J.T. Talks³, I. Sickle Eye Collaborative⁵

London North West University Healthcare NHS Trust¹, Moorfields Eye Hospital NHS Trust, London², Newcastle Hospitals NHS Foundation Trust³, Public Co-applicant⁴, Multicentre Research Group⁵

Background: Proliferative sickle cell retinopathy (SCR) is the most common cause of sight loss in sickle cell disease (SCD) and can result in significant sight loss, although the prevalence in the UK is unknown. There are 5 stages of SCR described¹; stages 1–3 are asymptomatic and stage 4 and 5 associated with significant visual loss often requiring surgical intervention with guarded outcomes.² Despite this well-described step-wise change, SCR screening in the UK is largely non-existent, with no national guidelines. The severity classification has remained unchanged for 50 years and may not reflect new insights on disease progression provided by modern imaging technologies. Laser treatment and intravitreal anti-vascular endothelial growth factor therapy have shown efficacy for treatment of stage 3 SCR but conclusive evidence is lacking.³ Retrospective evidence suggests hydroxycarbamide, used to prevent painful crises, has a protective effect against progression of SCR and maculopathy by elevating levels of fetal haemoglobin (HbF).⁴ Awareness of this protective effect, if confirmed, may have a significant positive effect on uptake and compliance of systemic treatment. In addition, ultrawide field fundus photography, optical coherence tomography (OCT) and OCT-angiography (OCTA) are relatively new retina imaging modalities proven to detect SCR and maculopathy more reliably than traditional eye examination⁵ and are amenable to automated retinal image analysis using artificial intelligence (AI).

Research question: What is the prevalence and impact of visual impairment due to sickle cell retinopathy and maculopathy in the UK?

Aims: The primary aim is to determine the prevalence of visual impairment (best corrected visual acuity ≤ 6/12) due to SCR and/or maculopathy in the UK.

Secondary Aims: 1. Determine prevalence of each stage of SCR and presence of maculopathy and correlation with (i) severity of SCD (ii) HbF level. 2. Determine impact of SCR and maculopathy on vision-related quality of life 3. Determine acceptability to patients of retinal imaging and routine screening for SCR and maculopathy 4. Develop updated severity classification system for SCR and maculopathy incorporating definitions generated by modern ophthalmic imaging technology. 5. Establish a database of retinal imaging amenable to automated retinal image analysis using artificial intelligence which may provide cost-effective and safe alternatives to a purely human grading system.

Design: Multi-center, prospective, cross-sectional, study funded by the NIHR RfPB funding stream.

Setting: 17 geographically-diverse NHS sites in the UK (Image 1).

Inclusion criteria: (1) Willingness to participate (2) Age ≥16 (3) Diagnosis of SCD of any genotype.

Exclusion criteria: Other causes of visual impairment such as cataract, glaucoma, and diabetic retinopathy.

Target sample size: At least 600 participants.

Methods: Participants will be identified in haematology clinics to reduce ascertain bias. Community engagement events in person and via social media will be used to promote the study to ensure community awareness and representative sample included. We will collect demographic data, systemic disease data and ocular history from all participants. All participants will have best corrected visual acuity, OCT, OCTA and ultrawide field fundus photography performed at their study visit. In addition, they will complete the NEI-VFQ 25 (a validated vision-related quality of life questionnaire) and a validated acceptability of retinal screening questionnaire at the end of the study visit.

Results: The study opened to recruitment in December 2023. 14 of 17 sites are now actively recruiting, with a further 3 sites still in set-up. So far, 141 participants (23.5% of overall sample size) have been recruited within 4 months of the study opening. The Sickle Eye research imaging database has been established with curation and labelling of images ongoing as received.

Summary: This is the first and largest multi-centre study on SCR in the UK and will deliver practice-changing insights to support improvement and standardisation of eyecare for people with SCD. Our project will also report on the vision-related quality of life in people with SCD, which is currently lacking in literature. Finally, our study will establish a world-leading Sickle Eye research imaging database, with curated access provided to national and international research groups, to support development of automated SCR grading and the use of retinal imaging to gain insights into systemic management in SCD in the near future.

1. MF Goldberg. Classification and pathogenesis of proliferative sickle retinopathy. American Journal of Ophthalmology, 1971; 71, 649–665.

2. J Ho et al. A comparison of 23 guage and 20 guage victrectomy for proliferative sickle cell retinopathy – clinical outcomes and surgical management. Eye (Lond), 2018; 32, 1449–1454.

3. KT Myint et al. Laser therapy for retinopathy in sickle cell disease. Cochrane Database of Systematic Reviews, 2015; (10), CD010790.

4. UK Mian et al. Elevated fetal haemoglobin levels are associated with decreased incidence of retinopathy in adults with sickle cell disease. British Society for Haematology, 2018; 183, 807–811.

5. T Alabduljalil et al. Retinal ultra-wide field colour imaging versus dilated fundus examination to screen for sickle cell retinopathy. British Journal of Ophthalmology, 2021; 105, 1121–1126.

Topic: 003–Clinical and epidemiological studies

A.G.M. Ismail¹, G.S.M. Ahmed¹, S.F.M. Bushara², A.J. Abdi³, O.S.M. Suliman⁴

Sudanese Medical Specialization Board¹, Khartoum University², Federal Ministry of Health³, International African University⁴

Background: Sickle-cell disease is a multisystem disease, associated with episodes of acute illness and progressive organ damage, and is one of the most common severe monogenic disorders worldwide. The most devastating neurologic manifestation of SCD is stroke. In thanks to advancements in early detection, prevention and management of SCD-related complications such as stroke, the quality of life and survival have been improved. However, less knowledge about SCD-related stroke types, risk factors, presenting symptoms and outcomes of patients.

Objectives: To study risk factors and outcomes of stroke among sickle cell disease children at Ibrahim Malik Hospital and Jaafar Ibn Ouf Hospital.

Methods: This is a cross-sectional hospital-based study conducted from May 2022 to November 2022 in two large hospitals in Khartoum, Sudan. The study population was all SCD children with stroke who are aged below 18 years. Data was collected using a data collection sheet filled from an interview, clinical evaluation and reviewing of tests after the obtainment of verbal consent from the caregivers. Analysis was conducted using SPSS version 26, and p < 0.05 were considered significant.

Results: A total of 93 SCD stroke patients were enrolled on the study, of those, most participants (64.2%) were aged more than 10 years old with male predominance (54.8%). Family history of SCD was present among (75.3%) of participants, while consanguinity between parents was present in (69.9%).

The majority of (38.7%) children were diagnosed with SCD at ages between 6 months and 1 year, while (52.7%) of participants had experienced a first stroke at the age of more than 5 years. (36.6%) had a past history of stroke. The majority of the patients 92 and few of them received a pneumococcal vaccine, influenza vaccine, and phenoxy benzylpenicillin, 23, 4, and 1 respectively. The most frequent neurological symptoms among the study group were speech disorders (68.8%) and convulsions (60.2%). Sensory symptoms were observed in (4.3%), weakness in (89.2%), hemiplegia in (74.2%), and cranial involvement in (53.8%). The vast majority of participants (88.2%) had infarction stroke and (5.4%) had hemorrhagic stroke type.

Most of the patients (63.4%) had a residual disability, (17.2%) of patients expressed partial recovery and (19.4%) of patients recovered fully. A significant association was found between adherence to prophylactic measures and the onset of disease (p = 0.04).

Conclusion: This study revealed several potential risk factors for stroke among SCD children, particularly irregular preventive medications. Furthermore, the study documented slightly high unfavourable outcomes of SCD stroke patients.

Topic: 003–Clinical and epidemiological studies

J. Sarmah¹, N. Basumatary¹

Bodoland University, Assam, India¹

Background: Sickle cell disease (SCD) and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency are two genetically independent as their loci are in chromosome 11 and X respectively. They are expected to assort independently. There are few reports on Co-existence of both. Interestingly, individuals having either of these conditions have less chance of being infected with malaria. The epidemiological data on associations of the two diseases are scare from Indian subcontinent.

Aim: This study aimed to determine associations (if any) between the two conditions or any other forms of haemoglobinopathy among the adolescents of Udalguri district in northeast India located in malaria endemic sub-Himalayan region.

Method: The study was approved by the Institutional Ethics Committee. The district was uniformly divided into 100 units and at least one village was randomly selected from each unit. Around 20 adolescents both male and female (10–19 years) from each village was selected and only one from a family. Informed consent was obtained from the guardians of the subjects.

G6PD deficiency was detected using STANDARD G6PD Analyzer (SD Biosensors) following the manufacturer's protocol. The device displays the amount of Hemoglobin (Hb) concentration in g/dL and quantitative value of G6PD level in U/g of Hb. The status of Hb and G6PD is interpreted by following WHO recommendations. 4 mL of blood samples were collected in heparinized vials by vein puncture in elbow fold from each individual who presented abnormality in either of the two values. The collected blood samples were used for detection of any form of haemoglobinopathy and further PCR-RFLP based molecular analysis for G6PD deficiency. Complete Blood Count was performed by Hematology Analyzer (Sysmex XP-100). Based on the CBC results, samples were selected for Hb-typing by using Capillary Electrophoresis (Sebia Minicap).

Results: Out of 2310 subjects, 1436 were found anaemic as per WHO protocol. All anaemic samples were subjected to Hb-typing. In Table I, it was observed that 448 samples carried the normal Hb but confirmed as anaemic due to non haemoglobinopathy reasons. HbS variant was observed in 473 samples, out of which 417 were HbAS and 56 were HbSS. 506 samples were observed with presence of HbE, 342 were HbAE trait and 164 were HbEE. Two samples were identified to have compound heterozygous condition for HbS and HbE. β-thalassaemia trait was observed in six samples. One sample was HbE - β–thalassemia trait. One case was detected with both G6PD deficiency and HbEE. We detected 86 cases with high HbF values.

Out of 2310 subjects, 144 were found to be G6PD deficient but asymptomatic. 66 were severely deficient and 78 were intermediates. The overall prevalence of G6PD deficiency was found to be 6.2%.

Summary: This large epidemiological study depicts data on prevalence of different types of haemoglobinopathy among the adolescents of the region which will help health system in managing the cases in future. The clinico-haematological features of high HbF cases are found to be unique in comparison to other reports. The study highlighted the co-occurrence of G6PD deficiency and HbE.

Conclusion: The study could not find any case of co-occurrence of SCD with G-6-PD. However; one case was detected on co-existance of G6PD deficiency A+ variant with HbEE.

Table I: Results of Hb typing of anaemic adolescents.

1. Basumatary et al. Journal of Medical Case Reports, 2021; 15, 386.

2. Babu et al. Pediatric Blood & Cancer, 2021; 68, 6.

3. Basumatary et al. Medical Journal Armed Forces India, 2023; 79, S394.

4. Babu et al. Journal of Medical Screening, 2023; 30, 28.

5. Basumatary et al. Exploratory Animal and Medical Research, 2021; 11, 43.

6. Basumatary et al. Biomedical and Biotechnology Research Journal, 2023; 7, 646.

Topic: 003–Clinical and epidemiological studies

M. Brito¹, C. Ginete¹, M. Mendes², R. Afonso², A. Siatembo³, J.N. Vasconcelos⁴, B. Inusa⁵

Health and Technology Research Center, Escola Superior de Tecnologia da Saúde de Lisboa, Instituto Politécnico de Lisboa¹, Hospital Materno Infantil Pedro Azancot de Menezes², CISA–Centro de Investigação em Saúde de Angola³, CISA-Centro de Investigação em Saúde de Angola⁴, Faculty of Life Sciences and Medicine, King's College London⁵

Background: Sickle cell disease (SCD) is a genetic recessive disorder, with a higher incidence in Sub-Saharan Africa. When undiagnosed 50%–90% of children will die under the age of 5. Therefore, early diagnosis is essential and allows to reduce drastically mortality and morbidity rates in children.

Aims: This project presents the implementation of a newborn screening for SCD, in one of the biggest maternities in Angola, Hospital Materno Infantil Dr Manuel Pedro Azancot de Menezes, and the follow up of the identified patients.

Methods: In June 2023, after ethical approval, the newborn screening started with the training in loco of all the health professionals involved. All the children born at the hospital Materno Infantil Dr. Manuel Pedro Azancot de Menezes (or vaccinated there) are invited to be included in the screening after parental consent. Blood is collected by heel prick test to filter paper. The samples are then sent to Lisbon (to H&TRC/ESTeSL/IPL) for hemoglobin electrophoresis by Isoelectric Focusing (IEF) in the equipment Migele (acquired with the support of Perkin-Elmer and Arise project). All the samples identified as being SS, are then confirmed by PCR-RFLP. After the diagnosis, parents are contacted so that the children may start follow up consultations in the Hospital, by a pediatric team, and start prophylactic therapies.

Results: Preliminary results show a prevalence of 1.4% of SS and 20.5% of carriers. From June 2023 to April 2024, 9121 dried blood spots were collected, 5265 were analyzed by IEF, and 73 children were identified as SS and contacted for follow up. During this period, and under the ARISE- project, 19 laboratory technicians from Angola and Nigeria were received in Lisbon for training in the IEF technique and molecular biology methods. In the future we intend that all the procedures associated with the newborn screening can be performed in the Hospital Laboratory by the technicians formed in Lisbon and also be replicated in other hospitals/maternities.

Conclusion: Our results corroborate the estimates of high prevalence of SCD in Angola, and demonstrate that the implementation of newborn screening for SCD is feasible and that it should be considered a priority. The follow up of these patients will for sure impact in their quality of life, as well as, in the rates of mortality and morbidity associated with this severe disease.

This study has been conducted within the African Research and Innovative initiative for Sickle cell Education (ARISE) that has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 824021. This project also has the financial support of FCT/MCTES H&TRC UIDB/05608/2020 e UIDP/05608/2020, e IPL/IDI&CA2023/Ipasthma_ESTeSL.

Topic: 003–Clinical and epidemiological studies

M. Brito¹, C. Ginete¹, T. Gomes², H. Pitangueira², M. Mendes³, A. Furtado³, L. Alves⁴, F. Simões⁴, G. Mauer⁵, J. Morais⁶

Health and Technology Research Center, Escola Superior de Tecnologia da Saude de Lisboa¹, Clincoord², Hospital Materno Infantil Pedro Azancot de Menezes³, Maternidade Lucrécia Paim⁴, Faculdade de Medicina da Universidade Agostinho Neto⁵, Centro de Investigação em Saúde de Angola, Instituto Nacional de Investigação em Saúde⁶

Background: Sickle cell disease (SCD) is marked by episodes of acute vaso-occlusive crises, severe anemia, acute chest syndrome, multi-organ damage and stroke, among others. Pregnancy in these patients is associated with an increased risk of adverse outcomes, such as intrauterine growth restriction, perinatal and maternal mortality, low birth weight, eclampsia, pre-eclampsia, and stroke. Therefore, increasing the surveillance during pregnancy and searching prophylactic solutions for early prevention of pregnancy complications in women with SCD in Low- and Middle-income countries, where the burden of SCD is disproportionally higher, is an urgent need.

Aspirin is already widely prescribed for the prevention of cardiovascular complications, and at a low daily dose, is used during pregnancy to prevent preeclampsia, intrauterine growth restriction, and other maternal-and-fetal disorders. In pregnant women with SCD, low dose aspirin is considered safe and is recommended for those who are at severe risk of pre-eclampsia.

Aims: LEARNER (ClinicalTrials.gov ID, NCT06417411), is a prospective, opened label study to evaluate the effects of daily low dose aspirin in pregnant women with SCD when initiated at the first trimester versus the second trimester of the gestational period (where it is frequently started). We hypothesize that a low dose of aspirin (100 mg/daily) initiated early in pregnancy (weeks 6–13) can be more beneficial, than when it is started in the second trimester (weeks 14–27), reducing the incidence of fetal and maternal complications. This study intends to quantify the reduction in preterm delivery, perinatal death/miscarriage, and the risk of other maternal complications including pre-eclampsia, hypertensive disorders, number of vaso-occlusive crises, need for blood transfusion, urinary tract infections, respiratory tract infections, acute chest syndrome, retained placenta, placental abruption, and vaginal bleeding, when initiating low dose aspirin in the earliest stage of the gestation period.

Methods: A total of 450 pregnant women, with confirmed diagnosis of SCD, will be enrolled in this study. Enrollment will take place in multiple maternity and infant hospitals in Luanda, Angola. Patients who consent to participate in the study will be assigned to one of two groups based on their gestational age, confirmed through ultrasound. Participants will then start daily use of 100 mg aspirin; dosing will be suspended at time of delivery, week 36, or earlier, if deemed necessary by the clinical team. Participants will be followed from the consenting visit to 6 weeks post-partum.

Results: Recruitment started in April 2024 after ethical approval (Parecer nº52/CEMS/2023, and 99/ARMED/MINSA/2024), and to date, 8 pregnant women with SCD were already enrolled.

Conclusion: This study also aims to build capacity in Angola for the conduction of future clinical trials, involving local research sites and hospitals, capacitating Angolan institutions and professionals in clinical trial conduction and data capture abilities, supporting the community, and creating patient awareness for clinical research studies.

The present project has the support of Calouste Gulbenkian Foundation and La Caixa Foundation Collaboration (We'Search).

Topic: 003–Clinical and epidemiological studies

E.M.C. Cegbeyi¹, O.D. Obed Danlami², A.O.O. Akinyemi Olugbenga Ofakunrin³, Demilade Olusola Ibirongbe⁴, S.O.A. Stephen Abah⁵, Baba Psalm Inusa⁶

African Research and Innovative initiative for Sickle cell Education (ARISE)¹, FCT Department of Mass Education, Garki, Abuja, Nigeria², Africa Research Innovative Initiative for Sickle Cell Education/University of Jos/Jos University Teaching Hospital, Jos, Niger³, University of Medical Sciences, Ondo⁴, Federal University of Health Sciences Otukpo, Benue State, Nigeria⁵, African Research and Innovative initiative for Sickle cell Education (ARISE) that has received funding from the European Union's⁶

Background: Sickle cell disease (SCD) is one of the most common inherited blood diseases worldwide. It is associated with significant morbidity and premature death, if untreated. About 312,000 people are born yearly with SCD globally and majority of these births occur in Sub-Saharan Africa, where early-life mortality due to the disease remains extremely high.

While the vast majority of the world's SCD burden occurs in sub-Saharan Africa, the United Kingdom has a sizeable population of individuals living with SCD. In the United Kingdom, in 2003, there were an estimated 17,500 people living with SCD and 300 babies born with the disease each year.

Considering the significant prevalence of SCD in the UK and its associated health burden, understanding public perception is vital for implementing effective health interventions and policies. A well-informed public is crucial for creating a supportive environment for individuals with SCD. Awareness and understanding can lead to better social support, reduce stigma, and improve the quality of life for those affected.

Objective: The study aimed to understand the general public's perception of SCD in London, United Kingdom.

Methodology: This survey utilized an intercept interview method to capture the perspectives of Londoners on SCD. Fifty adults in public places—streets, malls, buses and street corners across sub-regions of London (Central, North, East, West and South) were randomly approached and oral consent was taken. They were asked an open ended question, “What is sickle cell disease?” Their responses were recorded and analysed for their level of awareness and understanding of SCD; and these were presented using a frequency table.

Results: 50 adults participated and their responses are as shown in Table 1. Approximately 20% of the respondents demonstrated fragments of accurate information about SCD while 50% of the respondents have never heard of SCD.

Conclusion: The findings revealed a significant lack of awareness and numerous misconceptions about SCD among the respondents. The survey highlights a critical need for enhanced public education and awareness regarding sickle cell disease in London. Targeted health campaigns to improve understanding and support for those affected by SCD are required.

Table 1: Responses to the question? What is sickle cell disease?

This study has been conducted within the African Research and Innovative initiative for Sickle cell Education (ARISE) that has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 824021.

Topic: 003–Clinical and epidemiological studies

T.S. Noyes¹, N.G.A. Nanditha¹, K. Ershova¹, J. Fox¹, C. Chen¹, C. Teply¹, A. Harris¹, N.J. Kassebaum¹

Institute for Health Metrics and Evaluation¹

Background: Sickle cell disease (SCD) is well-recognized as a group of blood disorders that lead to serious multi-organ complications. However, the relative frequency and risk of health outcomes compared to those without any hemoglobinopathy has not been comprehensively described.

Aims: To estimate the disease frequency and relative risk of chronic and acute disease complications among patients with and without SCD diagnosis in the United States, overall and stratified by age, sex, and genotypes.

Methods: Longitudinal healthcare utilization and demographic information for years 2016 through 2019 was obtained from MarketScan (MS), a national health insurance claims database with data for patients with employer-sponsored health insurance standardized by Merative.^1–8 SCD diagnosis, overall and stratified by genotypes (HbSS, HbSC, HbSβ-thalassemia (mild and severe genotypes), and HbOS) was obtained using previously published algorithms.^9,10 ICD-10 codes were used to identify patients with cardiothoracic, urogenital, muscoskeletal, nervous, reticuloendothelial, oncological, infectious, and gastrointestinal conditions. Age- and sex-specific relative risks (for chronic conditions) and incidence rate ratio (for acute conditions) were calculated using meta-regression: bayesian, regularised, trimmed (MR-BRT), a meta-regression framework developed for the global burden of disease study.¹¹

Results: Individuals with SCD, regardless of genotype, had a significantly elevated prevalence and relative risk of nearly every health outcome we analyzed. Though some of these risks are well documented (e.g., stroke), this analysis found that individuals with SCD have elevated risks for other acute and chronic conditions, such as chronic kidney disease (RR = 4.39; 95% CI 2.78–6.95) and lower respiratory infections (RR = 2.22; 95% CI 0.90–5.43) compared to those without SCD. For conditions well-known to be sequelae of SCD such as vaso-occlusive crisis, a large relative risk (RR = 4023; 95% CI 4021–4025) was observed, as expected. The relative risk of most health outcomes was highest among younger age groups.

Summary/Conclusion: This retrospective cohort analysis identified strong, significant associations between SCD, regardless of genotype, and many adverse health outcomes. The increased risk of life-threatening health complications, particularly in children, indicates that screening is imperative for prevention.

Topic: 003–Clinical and epidemiological studies

K.L.E. Leigh-Ellis¹, L.W.E. Wellings¹, N.C.E. Constantinou¹

UCLH¹

The Sickle Cell and Thalassemia Alliance for Research (STAR) was set up to address the inequity of access to research in these disease groups across the North Thames CRN, particularly in paediatrics. UCLH has been active in Paediatric Sickle Cell and Thalassemia Research for 5 years, with 11 interventional and observational studies running. While Whittington Health has been able to support adult Sickle Cell and Thalassemia studies, it had a reduced capacity in paediatrics. Likewise, North Middlesex has not been able to support research in these disease areas in recent years.

Discussion and strategy meetings utilising a Hub & Spoke Model began in 2021 to set up the Alliance, with UCLH acting as the Hub. Two Paediatric Research Nurses started in post August 2023 bringing a wealth of skills and experience from previous research involvement and clinical care to the team. The STAR team meet regularly with the CRN to review progress, discuss issues and review processes to improve the operation of the Alliance.

This poster will explore some of the hurdles encountered in the birth of STAR, how these were overcome, where we are currently with supporting research across the three sites and the future of the STAR project. The number of studies we support continues to grow and engagement across the network has improved. By opening studies across sites, we improve the quality of research delivery gained by experience at each. We will demonstrate that the Alliance has been successful in increasing research activity and efficiency, not only in these diseases, but also in other areas for the teams we work with. The Alliance adds value to the R&D studies we work with and brings the opportunity for underserved communities to be involved in research, providing access to novel treatments with the potential to improve patients' lives.

Topic: 003–Clinical and epidemiological studies

K.M.C. Clarke¹, C.D. Dinah², M.V.S. Sarunic³, K.B. Balaskas⁴, R.A. Asaria¹

Royal Free Hospital¹, London North West University Healthcare NHS Trust², University College London³, Moorfields Eye Hospital⁴

Background: Sickle-cell disease (SCD) is a debilitating, multisystem condition characterised by episodes of acute illness, progressive organ damage, and reduced life expectancy.¹ Proliferative sickle cell retinopathy (SCR) is the most common cause of vision loss in SCD.² Optical coherence tomography angiography (OCTA) is a novel imaging modality enabling non-invasive assessment of retinal vasculature. Emerging evidence suggests that OCTA may be more sensitive in detecting SCR progression compared to existing techniques (Figure 1).³

Advancements in the field of oculomics also hold promise for linking quantitative OCTA metrics with systemic disease monitoring and response to treatment.⁴ This systematic review and meta-analysis provides a comprehensive evaluation of the role of OCTA in the diagnosis and management of SCR.

Methods: We searched MEDLINE/PubMed, Cumulated Index to Nursing and Allied Health Literature (CINAHL), SCOPUS and Cochrane Central Register of Controlled Trials (CENTRAL) electronic databases. The methodological quality of included studies was evaluated according to the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) recommendations.

Results: 31 studies met the inclusion criteria, and 26 suitably complied with the STROBE recommendations. Meta-analysis revealed that the foveal avascular zone (FAZ) was significantly larger in patients with SCR than in healthy controls (Figure 2), and mean vessel density of the superficial and deep capillary plexuses was significantly lower in patients with SCR than in healthy controls (Figure 3). A significant positive correlation was found between the temporal retinal thickness and superficial capillary plexus density in patients with SCR. There was no consistent association between OCTA findings and haemoglobin genotype, Goldberg staging² or visual acuity (Table 1).

Conclusion: OCTA can quantitatively detect retinal vascular remodelling in patients with SCR. Further research should focus on the clinical utility of OCTA for predicting SCR progression, providing insight into systemic disease monitoring, and assisting automation of SCR screening using machine learning techniques.⁵

Topic: 003–Clinical and epidemiological studies

M. Kontopoulou¹, C. Leboff², S. Chatzimatthaiou¹, C. Stephanou¹, M. Xenophontos¹, K. Orphanou¹, P. Kountouris¹, C. Lederer¹

The Cyprus Institute of Neurology & Genetics¹, Guy's and St Thomas' NHS Foundation Trust²

Background: Hemoglobinopathies are a group of inherited diseases arising from pathogenic variants within globin gene clusters, thereby influencing the synthesis and structure of hemoglobin. They encompass sickle-cell disease, thalassemia syndromes, and other rare blood diseases. Historically, hemoglobinopathies have been subjected to positive natural selection in regions experiencing high malaria transmission rates due to conferring protection against this infectious disease. However, human migration and interbreeding have rendered hemoglobinopathies a global health burden.

Aims: The primary objective of this study was to assess the global spatial distribution of the health burden caused by hemoglobinopathies.

Methods: To accomplish this goal, demographic and epidemiological data from registries, digital repositories and published literature were assimilated into a comprehensive, quality appraised and systematically biocurated dataset that will soon be incorporated into the IthaMaps database of the publicly available ITHANET¹ community portal. The dataset encompasses national and regional statistics on the prevalence and incidence rates of hemoglobinopathies, as well as the genetic diversity observed among affected individuals and carriers. Moreover, the dataset offers insights into the availability and nature of interventions for the management and prevention of hemoglobinopathies.

Results: To demonstrate the practical utility of this dataset and database, a Bayesian geostatistical modelling framework was employed on a subset of the data. This approach facilitated the generation of continuous, high-resolution maps depicting the predicted frequency of β-thalassemia variation across different regions. Additionally, it provided estimates of β-thalassemia patients in these areas.

Summary/Conclusion: By leveraging the database and estimation maps, healthcare practitioners and policymakers can gain access to an invaluable tool. This tool can facilitate the evaluation of current prevention and management strategies, enable the monitoring of trends over time, identify regions with a high burden of hemoglobinopathies, and inform data-driven policy decisions on the implementation of targeted interventions in these regions. In summary, the database and estimation maps offer a comprehensive and evidence-based approach to tackle and mitigate the global hemoglobinopathy burden, ultimately aiming to reduce its impact on affected populations.

1. Stephanou et al. ITHANET: an information and database community portal for hemoglobinopathies. Hemoglobin, 2019; 43(6), 363.

Topic: 003–Clinical and epidemiological studies

D. Canatan¹, S. Delibas², E. Altunsoy³, Y. Budak³, E.G. Gokkaya¹, S. Aydın⁴, D.A. Tuncel⁵, P. Thota⁶, U. Gurkan⁷

Antalya Bilim University¹, Hemoglobinopathy Diagnosis Thalassemia Center of Mediterranean Blood Diseases Foundation², Antalya Genetic Diseases Assessment Center³, Health Sciences University, Antalya Education and Research Hospital, Thalassemia Center⁴, Health Sciences University, Adana City Training and Research Hospital, Pediatric Hematology Oncology Clinic⁵, Hemex Health⁶, Case Western Reserve University⁷

Introduction: Haemoglobinopathies constitute the most common recessive monogenic disorders worldwide. They fall into two main groups: the thalassemia syndromes and the structural hemoglobin variants (abnormal hemoglobin). Recent estimates suggest that 7% of the world population are carriers and about 350,000 affected children are born every year. The majority of these (approximately 250,000) have sickle cell disease. The prevalence of these disorders is high in the Mediterranean Basin, some parts of Africa, the Middle East, India, Southeast Asia, Malaysia, and the Pacific Islands.

Current screening methods include complete blood count (CBC) high-performance liquid chromatography (HPLC) or capillary electrophoresis (CE). Molecular genetic confirmation by detecting pathogenic variants establishes the diagnosis. These methods require trained personnel and upgraded facilities, both of which may be lacking in many geographical areas where the disease is most prevalent. These standard laboratory methods also carry significant costs which may be unaffordable for most patients. Gazelle is the first miniaturized, paper based, microchip electrophoresis platform for identifying the most common hemoglobin variants easily and affordably at point-of-care in low-resource settings.

Aim: The aim of this study, to assess the performance of a low-cost, point-of-care (POC), microchip based cellulose acetate electrophoresis “Gazelle” compare to HPLC for premarital screening and confirmed the possible variants with beta gene sequencing

Material and Methods: In this study, couples who came to the Hemoglobinopathy Diagnosis Thalassemia Center of Mediterranean Blood Diseases Foundation (MBDF) for premarital thalassemia screening were enrolled. CBC and HPLC tests were performed on at MBDF. The remaining blood samples were performed Microchip Electrophoresis (GAZELLE®) at Antalya Genetic Diseases Assessment Center.

A total of 516 participants were screened with CBC, HPLC and microchip electrophoresis (Gazelle). Then, Beta gene sequence analysis was performed on the positive samples for confirmation. As a control group, CBC, HPLC, microchip electrophoresis (Gazelle®), and Beta gene sequence analysis were performed on 100 beta-thalassemia and sickle cell carriers.

Results: A total of 616 individuals participated in the study. Among the 516 individuals in the healthy group, 284 were women (55.1%), and 232 were men (44.9%), with an average age ± SD of 32.75 ± 11.25 years. A total 16 traits (3.2%) were identified as 14 beta-thalassemia trait, one Hb S, and one Hb D trait. The carriers consisted of 58 women (58%) and 42 men (42%), with an average age ± SD of 26.8 ± 18.6 years.

As a control group, 100 carrier individuals (81 beta-thalassemia and 19 sickle cell) were included. The carriers consisted of 58 women (58%) and 42 men (42%), with an average age ± SD of 26.8 ± 18.6 years.

Analyses for comparing the devices were performed using IBM SPSS Version 29 software. The Kappa Analysis method was used to measure the diagnostic sufficiency of the two devices. Both devices were found to be 100% consistent in diagnosis (Table).

Conclusion: Gazelle provides hemoglobin type identification and quantitative results of relative hemoglobin percentages for a broad range of hemoglobin variants including Hb A, Hb S, Hb F, and Hb A2, enabling accurate detection of β-thalassemia carriers. Gazelle has many advantages over other laboratory tests, including timely results (in <8 min), digital storage, wi-fi connectivity, portability and printed reports.

Table: The result of both device.

Topic: 003–Clinical and epidemiological studies

R.M. Aliyu¹, N. Adebiyi¹, A.D. Waziri¹, I.Y. Tabari¹, I. Halilu¹, I. Abdulkadir¹, H.R. Ahmad¹

Ahmadu Bello University Teaching Hospital, Zaria-Nigeria¹

Introduction: Sub-Saharan Africa has the highest burden of sickle cell disease (SCD) and less than 50% survive beyond the fifth year of life. Nigeria stands out as the most endemic SCD country. Newborn screening (NBS) for SCD enables early diagnosis and enrolment in to comprehensive management. Pregnant women are important stakeholders in the control measures of SCD like prenatal diagnosis and NBS. Newborn screening for SCD is yet to be widely available in the Nigeria.

Objectives: To determine the awareness, acceptability and factors associated with NBS for SCD among pregnant women.

Methods: A descriptive cross-sectional study involving 210 attendees of antenatal clinic of Ahmadu Bello University Teaching Hospital Zaria. An interviewer-administered structured questionnaire was used to obtain information about socio-demographic characteristics, awareness and acceptability of NBS. The data was analysed using SPSS version 21. Fisher–exact test was used to test associations between variables. The level of significance was set at p < 0.05.

Results: The mean age of participants was 28 ± 6.3 years. The majority of the women (79.5%) were of Hausa ethnicity, 48.6% had tertiary education, 70.5% had a personal source of income and 6.2% had a rural residence. The majority (60.5%) of the women were aware of NBS for SCD and 96.7% were willing avail their babies to NBS, mostly (68.6%) within the first 24 h after birth. However, more than two-thirds of the women will need to obtain permission from their spouses before allowing their babies to be tested, even when the test is free of charge. Young age (<35 years), nulliparity, low educational level, socioeconomic status, tribe and religion were associated with awareness of NBS for SCD (p < 0.05). These factors except parity were also associated with willingness to accept NBS (p < 0.05).

Conclusion: Many pregnant women were aware of NBS and the majority of the women were willing to accept the testing especially in the early postpartum period. Many socio-demographic characteristics were associated with willingness and acceptability of NBS.

1. Moeti et al. The Lancet Haematology, 2023; 10(8), e567–e569.

2. Adigwe et al. The Journal of Blood Medicine, 2023; 31(14), 367–376.

3. Green et al. Blood Advances, 2022; 6(24), 6187–6197.

Topic: 003–Clinical and epidemiological studies

J. Bertello¹, D. Di Grazia², C. Mirabella², F. Chiara², M. Caudana², F.M.A. Shelton Agar², M. Zanatta³, S. Allegra², G. Abbadessa², S. De Francia², V. Voi¹

Department of Clinical and Biological Sciences, SSD Microcythemia and Rare Haematological Diseases, University of Turin, S. Luig¹, Department of Clinical and Biological Sciences, Laboratory of Clinical Pharmacology “Franco Ghezzo,” University of Turin, S. Lui², Department of Economics and Statistics³

Introduction: Hydroxyurea (HU) is the primary pharmacological therapy for sickle cell disease (SCD). Its effectiveness lies in enhancing fetal hemoglobin (HbF) expression, preventing red blood cell sickling. Achieving optimal HbF induction involves carefully selecting and maintaining the appropriate dose, with gradual escalation until reaching the Maximum Tolerated Dose (MTD). A pharmacokinetics-guided dosing approach aims to achieve better clinical responses more efficiently than the current standard practice.

Aims: The primary objective of this study was to develop the pharmacokinetic measurement of HU. Secondly, we sought to identify the most informative sampling time, thereby minimizing the required number of blood collections.

Methods: After developing a valid measurement method of HU, we conducted an exploratory study of pharmacokinetic (PK) in a group of SCD patients. Patient received their usual dose after a washout of 48 hours. Sample were collected at 0, 2, 4 6, and 24 h. In our investigation with both adult and pediatric patients, we sought to identify the most informative sampling time, thereby minimizing the required number of blood collections.

Results: PK was conducted in 80 patients (F:M 42/38). The mean age was 17.3 ± 13.9 years (range 2.3–73). Eight patients (10%) had never taken HU before. The mean dose was 19.5 ± 5.1 mg/kg (range 7.7–37.5). The mean AUC was 122.1 ± 7.9 mg/L/h (range 22.7–355.9). We did not observe a relationship between AUC and the dose administered in mg/kg (r = 0.07; CI_95% = −2.1–4.1; p = 0.52). We observed a very strong correlation at 2-h, 4-h, and 6-h time (r_t2 = 0.93; r_t4 = 0.92; r_t6 = 0.91; R² = 0.93; p < 0.0001). Using a 3-point samples PK study we can strongly predict patients' AUC (see figure).

Conclusions: The lack of a significant relationship between AUC and the dose administered in mg/kg suggests that individualized dosing may be necessary and that further studies are necessary to better comprehend the pharmacology of HU. Previous studies focused predicting AUC from a single PK point. A 3-point PK prediction of AUC is more precise and does not impact heavily on patients. Tailoring dosages based on individual characteristics can enhance treatment outcomes and reduce the risk of adverse events.

1. RE Ware et al. Hematology American Society Hematology Education Program, 2015, 436-443.

2. M Dong, PT McGann. Clinical Pharmacology & Therapeutics, 2021; 109(1), 73-81.

3. C Nazon et al. Journal of Clinical Medicine, 2019; 8(10).

Topic: 003–Clinical and epidemiological studies

L. Figueira¹, A. Salvada¹, M.F. Silva¹, J. Monteiro¹, A.P. Ventura¹, C. Escobar¹, T. Ferreira¹

Departamento da Criança e do Jovem, Hospital Prof Doutor Fernando Fonseca¹

Background: Children living with sickle cell disease (SCD) frequently use the pediatric emergency department (PED) due to the morbidity of this disease. The severity of acute complications of SCD varies widely.^1,2

Aim: Our aim was to characterize PED visits among patients with SCD.

Methods: This retrospective observational study was conducted at a PED of a general hospital in the suburbs of Lisbon, Portugal. We analyzed PED visits of patients with ages between 0 and 17 years and 364 days with SCD under follow-up in hospital outpatient consultations between 1st January 2021 and 31st December 2023. Data were collected from clinical records. SPSS version 29 was used for statistical analysis.

Results: Among 200 patients included, 50% were male, 90.5% had HbSS genotype, 55% were born in Portugal and 90% had an african origin (45.8% Angola, 20.25% Guinea Bissau, 11% from Sao Tome and Principe, 10% Cape Verde). 161 patients (80.5%) visited the PED during the study period, totaling 848 PED visits. The median visits per patient was 4 (IQR 2-7). The median age was 6.6 years (IQR 2.4–11.6).

According to the Manchester Triage System (MTS) risk rating, the Standard category was the most prevalent (47.4%), followed by Urgent (35.7%) and Very Urgent (16.4%). The predominant flowchart categories were “worried parents” (19.6%), “limb problems” (16.5%), “abdominal pain” (9.6%), and “lumbar pain” (7%). The most common discriminators were moderate pain (20.5%), recent problem (17.3%), and mild pain lasting less than 7 days (15.4%).

Patient-reported pain was assessed in 95,8% of the visits, 61.2% reported experiencing pain: mild (1–4/10) in 26.7%, moderate (5–7/10) in 25%, and severe (8–10/10) in 9.5%. 57.3% had already started pain relief medication at home either with paracetamol/ibuprofen or both. For moderate or severe pain, analgesic prescription in PED included cetorolac (43.8% and 68.8%, respectively) and opioids (16.3% and 41.6%).

The median time to first observation was 16 minutes (IQR 7–35) and median PED stay was 167 min (IQR 92–244). Most episodes required a blood analysis (64.9%), mainly when a SCD-related diagnosis was made (89.9% vs. 46.6%, p < 0.001).

Most PED visits were not related to SCD acute complications (491, 57.9%). Most frequent non-SCD diagnoses were: 149 upper respiratory infection (17.6%), 108 other infection (12.7%), 33 trauma (3.9%), 24 acute gastroenteritis (2.8%). The main SCD-related diagnoses were: 267 acute painful crisis (31.5%), 32 sequestration (3.8%), 25 acute chest syndrome/pneumonia (2.9%), 24 acute anemia (2.8%), 9 neurological event (1.1%). Hospital admission was required in 36.8%, more frequently when an SCD acute complication diagnosis was made (67.5% vs. 14.5%; p < 0.001).

Conclusions: A considerable proportion of SCD patients' visits to PED are due to pain,^1,3 with a remarkable number requiring hospital admission. The data underscores the necessity for tailored interventions to enhance overall care for SCD patients in the emergency setting, namely improving timely analgesia choice. An SCD PED pathway of care implementation could help in reducing the gap between patients' needs and care provided. Further research should be done to improve the quality of care for patients with SCD.

Topic: 003–Clinical and epidemiological studies

L.S. Sahakyan¹, N.A. Melkikyan¹, M.S. Badikyan¹, M.G. Melik-Andreasyan¹, A.A. Voskanyan¹, L.M. Krmoyan¹, L.H. Vagharshakyan¹, H.G. Grigoryan¹, A.M. Hovhannisyan², H.S. Khachatryan¹

Yeolyan Hematology and Oncology Center¹, Genetic Forensic Center LLC²

Background: Thalassemia is a significant hereditary hemolytic anemia with substantial implications for individuals and healthcare systems. In Armenia, the diagnosis and treatment of thalassemia have evolved significantly in recent years.

Methods: This study focuses on patients diagnosed and treated at the Yeolyan Hematology and Oncology Center, the only medical facility in Armenia dedicated to diagnosing and treating both malignant and benign blood disorders.

Results: Until 2018–2019, diagnosing hereditary hemolytic anemias in Armenia was challenging due to limited genetic testing. Only pediatric patients with homozygous thalassemia had their diagnosis confirmed through genetic analysis (thalassemia strip assay), but adult patients without insurance or financial resources struggled to receive accurate diagnoses. Cases of spherocytosis were correctly identified, while other cases were often presumed to be thalassemia without definitive confirmation. This lack of modern diagnostic tools hindered accurate disease characterization, especially in adults, leading to only 3–5 cases of thalassemia being registered annually.

Carrier testing data (Oberkanins et al., 2021) suggests low frequencies in Armenia and Georgia, which does not align with our database. Since 2019, significant progress has been made in medical diagnostics in Armenia. Automation of laboratory equipment and expanded testing panels, including electrophoresis and genetic testing, has revolutionized diagnostics, leading to the accurate diagnosis of 35–45 new cases of thalassemia annually. Increased detection is due to thorough examinations of conscripts, pregnant women, and displaced individuals from Nagorno-Karabakh. These advancements have significantly improved patient outcomes through timely disease detection. However, many cases of heterozygous thalassemia remain undetected. Establishing a separate benign hematology unit and introducing new diagnostic and therapeutic protocols aim to address this issue.

Current treatments in Armenia include blood transfusions, hydroxyurea, chelation therapy, and bone marrow transplantation. Other advanced methods of treatment are not yet available to the Armenian patients.

Conclusion: Since 2019, the implementation of stripe PCR for thalassemia diagnostics and the possibility to outsource up-to-date genetic testing have significantly improved the identification and treatment of thalassemia in Armenia. Despite improvements, broader access to diagnostic tools and advanced treatments is needed. Ongoing efforts to establish dedicated units and protocols are expected to further enhance the management and outcomes of thalassemia patients in Armenia.

1. C Oberkanins et al. Georgian Medical News, 2021, (318), 124–128.

Topic: 003–Clinical and epidemiological studies

P. Flevari¹, A. Balassopoulou¹, S. Chatzidavid¹, E. Boutou¹, V. Bartzi¹, E.E. Delaki¹, E. Yfanti¹, A. Kopsaftopoulou¹, G. Anastasiadis¹, M.N.D. Dimopoulou¹

Laikon General Hospital of Athens¹

Introduction: Thalassemia intermedia is a very heterogenous condition. The clinical diversity ranges from non-transfusion dependent (NTDT) thalassemia with minimal comorbidities burden, to severe complications and evolution to transfusion dependency (TD). Genotype and degree of anemia are the major factors defining clinical severity. Mild variants (β++ and βsilent) usually result in milder clinical profiles when coinherited with β+and β0 variants but the phenotype is not always predictable.

Aim: The aim of this study is to document the impact of β++ and βsilent on phenotype of TI patients and provide data for genetic counseling.

Methods: Clinical and laboratory data were collected retrospectively from medical files of TI patients (pts) in an adult center of expertise. Hb fractions were measured by High Performance Liquid Chromatography (HPLC). Genotyping was performed with traditional molecular methods. Only patient with genotypes including β++ and βsilent variants are included.

Results: In our site 99 thalassemic pts have including genotypes including β++ and βsilent variants. Clinical profile (including TDT vs NTDT status, age of transfusion initiation, age at diagnosis, number of complications) for different genotypic subgroups is shown in table 1.

More detailed laboratory data at diagnosis and complications according to genotype are presented in Figure 1.

Conclusions: Pts with IVSI-6 T>C genotype may become TD early in life and have a significant burden of complications even if they remain NTDT as adults. A minority of pts with -87 C>G genotypes may become TDT in adulthood. Pts with βsilent variants have a very mild clinical picture. They are diagnosed late in life and do not suffer from many comorbidities. Only rarely do they become TDT late in adulthood. Especially in NTDT pts with genotypes including +1570 T>C the clinical picture resembles to that of healthy heterozygotes. However, +1480 C>G is an exception among βsilent variants as it leads to a more severe phenotype with comorbidities. These data are useful for population-based carrier screening strategies aiming at silent mutation detection and for accurate genetic counselling of couples of carriers. Identification of genetic modifiers will help to further define prognosis.

1. SL Thein. Cold Spring Harbor Perspectives in Medicine, 2013; 3(5), a011700.

2. Boussiou et al. Blood Cells, Molecules and Diseases, 2008; 40(3), 317–319.

3. Kountouris et al. The American Journal of Hematology, 2021; 96(11).

Topic: 003–Clinical and epidemiological studies

P. Flevari¹, S. Kyriakaki², S. Chatzidavid¹, A. Balassopoulou¹, E. Boutou¹, E.E. Delaki¹, E. Yfanti¹, I. Tobrou¹, E. Klironomos², M. Dimopoulou¹

Laiko General Hospital¹, Venizeleio Hospital of Heraklion²

Introduction: Hemoglobinopathy H (HbH) is a rather heterogeneous disease in terms of genotypic diversity and clinical severity. Specific variants and genotypes frequencies varies among ethnic groups. Information about genotypic and clinical profiles are useful for screening strategies applied to specific populations and appropriate genetic counselling.

Aim: The aim of this study was to report genotypic and clinical characteristics of Greek patients (pts) with HbH.

Methods: Clinical and laboratory data were collected from pts' medical files in two sites in Greece: an expertise center in Athens and a unit in Heraklion Crete. Clinical severity parameters reported include transfusion status (transfusion dependent, TD vs. non-transfusion dependent, NTD) and other complications. Genotyping was performed by traditional molecular techniques.

Results: In the two sites 79 pts with HbH are followed, 60 in Athens and 19 in Crete. The median age is 40 years (range 4–85), and 45 are female. Median age at diagnosis was 21 yrs (range: at birth-73 years) Median Hb at initial presentation was 9.35 g/dL (range 7.3–12 g/dL). Only 5/79 (6.3%) were TD whereas 74/79 (93.7%) were NTD. Splenomegaly was found in 80% pts. The reasons for regular transfusion initiation (RTI) were severe anemia in 3/5 pts, pulmonary hypertension in 1 and severe cardiac dilatation in 1. Occasional transfusions were required in 24 pts (30%) whereas 55/79 (70%) have never required a transfusion in their life. The main reasons for occasional transfusions were pregnancy, surgery or infections. Splenectomy has been required only in 5 pts (6.3%) because of anemia and/or hypersplenism. All splenectomized pts have responded with a sustained, long term Hb improvement. Among the TD pts, 4 receive chelation therapy, while among the NTD only 2 pts have required chelation therapy.

Genotype was available in 60/79 pts. The majority of pts (37/60) had two deletional variants 7/60 had a combination of deletional and non-deletional variants and 16/60 had two non-deletional variants. Clinical and hematologic characteristics of different genotypic groups are shown on Table 1. Only one pt homozygous for αAgrinioα, a rare non deletional variant found in Greece, was TD since birth. Two more pts with non-deletional genotypes including the ααTaybe, a variant resulting in an unstable Hb, one pt with non-deletional genotype and one with unknown genotype became TD in adulthood.

Conclusions: Hemoglobinopathy H is a mild clinical condition in the majority of cases, that requires follow-up without regular transfusions. Splenectomy is rarely required to correct anemia, especially in αPA1α/αPA1α pts, with good response. Progression to TD is very rare, observed only in non-deletional genotypes. RTI in early childhood was observed only in one pt, homozygous for the rare non-deletional variant αAgrα. The majority of pts with deletional genotypes common in Greece have less severe anemia, may never require transfusions and do not progress to TD. These data can facilitate genetic counseling of couples of heterozygotes of Greek origin.

1. Musallam et al. Αlpha-thalassemia: a practical overview. Blood Review, 2024; 64, 101165.

Topic: 003–Clinical and epidemiological studies

E.J. Baartmans¹, M. Bruinooge¹, S.E. Luijnenburg¹, M.L. Geurtsen², M.H. Cnossen¹

Department of Pediatric Hematology and Oncology, Erasmus MC Sophia Children's Hospital, University Medical Center¹, Department of Pediatrics, Erasmus MC Sophia Children's Hospital, University Medical Center²

Background: In homozygous HbSS sickle cell disease (SCD), an elevated time-averaged maximum mean velocity (TAMMV) on transcranial Doppler (TCD) examination is associated with an increased risk of arterial ischemic stroke (AIS). These criteria are also applied for compound heterozygous HbSC SCD, but are not universally used across treatment centers.

Aims: This study aims to establish reference values and best practices for the clinical management of potential neuroradiological anomalies in children with HbSC SCD by evaluating TCD results and patient outcomes.

Methods: This retrospective single center cohort study was performed in the Erasmus MC Sophia Children's Hospital. Children diagnosed and treated for HbSC SCD between January 1st 2017 to December 31st 2022 at the Sickle Cell & Thalassemia Comprehensive Care Centre were included. Data on patient characteristics, TCD standard, and TCD Duplex screening results were collected. In our analyses, MCA measurements by application of TCD standard, and both MCA and ICA by application of TC Duplex were compared to proposed alternative reference values in literature for HbSC and Stroke Prevention in Sickle Cell Anemia (STOP) criteria, mainly based on HbSS and HbSβ0 data.

Results: Within the study period, 31 children with HbSC SCD were identified. Mean age at first TCD screening was 2 years. Of the 133 expected TCD screenings a total of 96 (72%) TCD standard and 93 (69%) TC Duplex were performed. Fourteen out of 519 (2.7%) measurements exceeded reference values in the literature for HbSC SCD, but none exceeded the STOP- criteria for HbSS SCD. No AIS occurred in the study population. Subsequent MRI-MRA was performed in 1 case, due to remarkably low flow rates instead of high flow rates. Hydroxycarbamide was initiated in 4 out of 31(12.9%) cases due to specific clinical conditions and no chronic blood transfusion regimens were initiated.

Conclusion: In this study, TCD measurements infrequently exceeded HbSC TCD reference values, and no AIS were observed, but never the STOP criteria. These findings suggest that routine TCD screening may indeed not be necessary for children with HbSC SCD.

Topic: 003–Clinical and epidemiological studies

P.A. Glancy¹, C. Bagot¹, A. Klauser², B. Robertson³, G. Marron⁴, V. Brace⁵, A. Gibson¹, L. McIlwaine¹

Department of Haematology, Glasgow Royal Infirmary¹, Department of Haematology, Royal Infirmary of Edinburgh², Department of Haematology, Aberdeen Royal Infirmary³, Department of Haematology, Ninewells Hospital⁴, Department of Obstetrics and Gynaecology, Glasgow Royal Infirmary⁵

The population of Scotland has diversified significantly within the last two decades, and consequently the number of patients with Sickle cell disease (SCD) has increased. A multi-system disorder, this condition is associated with significant morbidity and mortality—risks which are heightened during pregnancy.¹ Pregnant patients with SCD are at increased risk of sickle-related complications, pregnancy complications, and have a higher maternal and fetal mortality.³ The British Society of Haematology (BSH) recommendations state that all should be managed by a specialist MDT with shared care between haematology and obstetrics.⁴ Organising such a service in areas of low prevalence is challenging, but this has been developed in areas of Scotland over the last decade. Studies have previously reviewed pregnancy outcomes in SCD across the UK,⁵ but no specific review of Scottish SCD pregnancies has been undertaken.

In this study, we reviewed the key aspects of all SCD pregnancies across Scotland in the last fifteen years. This included phenotype, management during pregnancy, sickle complications, pregnancy complications, transfusion requirements, mode of delivery and both maternal and fetal outcomes. We also reviewed our how well our national practice aligns with the 2021 BSH guideline for management of SCD in pregnancy, while noting that many patients in this cohort delivered prior to the release of this guideline.

Patients were primarily identified through clinician recollection, as no specific database is currently held for SCD pregnancies within Scotland. Data was collected for patients who delivered between 2010 and 2024 respectively from the four haematology tertiary centres in Scotland- Glasgow, Edinburgh, Aberdeen and Dundee. This was obtained through retrospective review of patient medical notes, both electronic and written depending on patient location.

Since 2010, there have been 57 pregnancies in 55 patients with SCD across Scotland. This has resulted in 45 live births (1 twin pregnancy) with 6 ongoing pregnancies, 2 lost to follow-up, 1 miscarriage, 1 termination of pregnancy and 2 fetal deaths. 23 (42%) were women with HbSS, 30 (55%) were women with HbSC, one woman had a diagnosis of HbS/Beta-0-Thalassaemia and one had a diagnosis of HbSD-Punjab. Gestation at delivery ranged from 29 weeks to 39+4 weeks. Data was also collected in relation to management during pregnancy including VTE prophylaxis and imaging, sickle-cell crises including admissions and management, pregnancy-related complications and transfusion, including products used and antibodies developed. Outcome at delivery including birth weight will also be presented.

In summary, this is the first national review of pregnancy outcomes in patients with sickle-cell disease in Scotland. In reviewing our outcomes, we hope to identify areas of unmet need where we can focus resources to improve outcomes for our patients.

Topic: 003–Clinical and epidemiological studies

A.G.M. Ismail¹, M.E.I. Elnour¹, A.A.M. Alagib², D.M.Y. Elfaki³, A.M.S. Salih⁴

Sudanese Medical Specialization Board¹, University of Medical Science and Technology², Cavan General Hospital-HSE³, Omdurman Univesity⁴

Background: Sickle cell disease (SCD) is a multisystem disease, associated with episodes of acute illness and progressive organ damage, and is one of the most common severe autosomal recessive disorders worldwide.¹ Painful episodes are a major cause of morbidity and organs damage in SCD.² Dactylitis is often the initial presenting symptom of the disease in the form of pain, but SCD-related pain also frequently affects the chest, abdomen, and long bones.³ SCD associated pain is characterized by a complex pathophysiology involving the abnormal sickling of red blood cells (RBCs) due to polymerization. These rigid sickled cells adhere to endothelial cells and increase blood viscosity cannot flow smoothly through blood vessels, which leading to vaso-occlusive crises, tissue ischemia and subsequent organ damage.³

The outcomes of sickle crisis pain are influenced by many factors and can affect the quality of life (QoL) of patients in terms of emotional, behavioural and psychological responses. Furthermore, many patients who experience sickle-related pain are aware of the danger of premature death with sickle cell disease.⁴ Age, social and ethnic group, the intensity of pain and genotypes are the factors considerably associated with worse pain outcomes in SCD patients.⁵ In Sudan 1988, Bayoumi et al. assessed the frequency of pain in 50 SCD patients and found that the observed pattern of SCD is comparable to the severe type described for African nations. Whereas, age, severe anaemia, malnutrition and infection are the aggravating factors of SCD pain among this cohort.⁶ However, there is a deficiency in updated data addressing SCD-related pain characteristics, management, and outcomes of patients in Sudan.

Aim: To study pain characteristics, management and outcome among sickle cell anaemia patients in a tertiary hospital, Khartoum, Sudan, 2018–2021.

Methods: This is a cross-sectional hospital-based study. The study was based on the extraction of the patients' data from their Hospital records retrospectively from January 2018 to December 2021 in Ibrahim Malik Tertiary Hospital in Khartoum, Sudan. The study population was all SCD children who are aged below 18 years and have completed medical records.

Simple random sampling method was used to recruit the study participants who fulfilled the study criteria. The sample was divided equally between 4 years of study duration and there for 36 patients' records were randomly selected for each year. Informed consents have been taken from parents or caregivers to collected data by using pre designed data collection sheet in which demographical data, clinical factors, pain frequency, pain characteristics, management and outcome data.

Results: A total of 354 SCD patients were admitted to Ibrahim Malik Hospital over 4 years of study period. Of these 141 were enrolled to the study. The majority of them 75 (59%) were less than years in age with male: female ratio of 2:1.

Clinically, the majority of the participants 140 (97.2%) used to take folic acid supplementations and hydroxyurea. Most of them 109 (75.7%) had regular follow up and all of them reported recurrent admission.

The frequency of pain among our participants was 71 (49.3%). Most of the pain was occurred the upper limb 42 (59.2%), lower limbs 34 (47.9%), abdomen 16 (22.5%), chest 2 (2.8%) and back pain 4 (5.6%). Most of them reported severe degree of pain 41 (57.7%), and moderate 30 (42.3%). The most common pain-associated symptoms were fever 36 (53.5%), cough 2 (2.8%) and SOB 2 (2.8%). The pain was aggravated by fever 28 (39.4%) and dehydration in 3 (4.2%), with while relieved with analgesics use in 60 (84.5%) and with rehydration 11 (15.5%).

The majority of the participants received NSAIDs 61 (85.9%), Paracetamol 16 (22.5%) and morphine in 2 (2.8%). Some participants received blood transfusion 22 (31%). In regards to the pain management outcome, the study showed that 69 (97.2%) of them were relieved, and only 2 (2.8%) were partially relieved with no complications. Nearly two-thirds of the 67 (94.4%) reported a hospital stay for 3–7 days. Apart of gender (p = 0.409) the occurrence of pain was most strongly associated with younger age (p = 0.034), rural residence (p = 0.001), non-prophylaxis use (p = 0.04), and irregular follow up (p < 0.001).

Conclusion: This study revealed that the severe pain pattern is the commonest among SCD children in Sudan. While several potential risk factors were identified for SCD related pain in children, particularly younger age, rural residence, non-prophylaxis use, and irregular follow up have been significantly associated with pain. Furthermore, the study documented relatively high use of RBCs transfusion in management of SCD associated pain. However good related outcomes among this cohort have been recorded.

1. D Weatherall et al. A case for developing North-South partnerships for research in sickle cell disease. Blood, 105, 921–923.

2. A Ismail, BPD Inusa. Effectiveness of comprehensive newborn screening program of sickle cell disease on the childhood morbidity and mortality of the disease: a systematic review and meta-analysis. Blood, 2020; 136, 11.

3. C Elendu et al. Understanding sickle cell disease: causes, symptoms, and treatment options. Medicine (Baltimore), 2023; 102(38), e35237.

4. R Dunlop, KCLB Bennett. Pain management for sickle cell disease in children and adults. Cochrane Database of Systematic Reviews, 2006; (2).

5. MO Kenney et al. Biopsychosocial factors associated with pain and pain-related outcomes in adults and children with sickle cell disease: a multivariable analysis of the GRNDaD multicenter registry. Journal of Pain, 2024; 25(1), 153–164.

6. RA Bayoumi et al. Sickle cell disease in Sudan. Transactions of the Royal Society of Tropical Medicine and Hygiene, 1988; 82(1), 164–168.

Topic: 003–Clinical and epidemiological studies

M. Xenophontos¹, C. Bento², C. Stephanou¹, J. Pereira², C.W. Lederer¹, P. Kountouris¹

Molecular Genetics Thalassaemia Department, The Cyprus Institute of Neurology and Genetics¹, Centro Hospitalar e Universitário de Coimbra²

Background: Diseases that impact hemoglobin synthesis and function are common globally. Over 1500 structurally abnormal hemoglobin (Hb) variants have been reported in databases like the ITHANET portal. These variants can alter hemoglobin structure and biochemical properties, leading to physiological effects that range from insignificant to severe. However, the terminology used for these structural variants often lacks clarity, merging the variant's impact on protein properties with the mode of disease inheritance (e.g., Thalassemia dominant variants). To address this issue, we initiated the development of a glossary aimed at providing distinct definitions for terms commonly used in the field.

Aims: This study aims to produce a glossary that separates the description of a variant's effect on hemoglobin structure from its diagnostic or clinically detectable phenotype across various genetic contexts—heterozygotes, homozygotes, and compound heterozygotes. Additionally, we aim to refine variant annotations obtained from the ITHANET portal.

Methods: We collaborated with experts in structural hemoglobinopathies to develop a glossary. Using this glossary, we extracted case-level data from the IthaPhen database of the ITHANET portal, for specific groups of structural hemoglobin variants with well-documented clinical manifestations. We then evaluated the concordance between the curated annotations for these Hb variants and the clinical phenotypes reported in the corresponding cases. Additionally, we conducted a literature search to compile globin chain positions crucial for α1β1 and α1β2 contacts and integrated this information with ligand binding sites retrieved from UniProt and variant data from the ITHANET portal.

Results: We refined variant annotations on the ITHANET portal based on the assessment of agreement between curated annotations and clinical phenotypes. The compiled globin chain positions crucial for α1β1 and α1β2 contacts, along with ligand binding sites, provided insights into regions on the globin chains associated with specific protein properties, such as low or high oxygen affinity and sickling tendencies. Notably, structural modifications that result in high oxygen affinity were predominantly located at the α1β2 interface or the C-terminal. In contrast, unstable hemoglobin variants did not exhibit a specific localization pattern around particular elements of the globin chain.

Summary/Conclusion: Our efforts have led to the development of a glossary that provides clear and distinct definitions for terms commonly used in the field of structural hemoglobin variants. This glossary, along with the refined annotations on the ITHANET portal, enhances the clarity and quality of data related to hemoglobin variants.

Funding: This study was supported through a Short-Term Scientific Mission grant from HELIOS-COST (CA22119)

1. M Xenophontos et al. HemaSphere, 2023; 7, e922.

2. P Kountouris et al. PLoS One, 2014; 9, e103020.

Topic: 003–Clinical and epidemiological studies

M.A. Minaidou¹, X.M. Xenophontos¹, S.C. Stephanou¹, T.S. Tamana¹, K.M. Kleanthous¹, L.C.W. Lederer¹, K.P. Kountouris¹

The Cyprus Institute of Neurology and Genetics¹

Background: Haemoglobinopathies are the commonest monogenic diseases, with approximately 6% of the world's population carrying a pathogenic globin gene variant. Over 3400 disease-causing variants have been associated with haemoglobinopathies, according to the IthaGenes¹ database with varying severity and clinical presentation. Many of these variants are rare thus their effect on the globin-genes function is unclear and currently unavailable. Notably, haemoglobinopathy-specific databases, provide limited phenotypic information about curated variants in tabular or text format. However, this information covers only a small fraction of reported variants and their observed genotypic combinations and, therefore, their utility for variant interpretation is limited.

Aims: The correlations between genotype and phenotype can give us a deeper understanding of the pathogenesis of haemoglobinopathies and facilitate a comprehensive prenatal genetic counselling of the carriers. Therefore, we develop the first haemoglobinopathy specific Genotype–Phenotype database (https://www.ithanet.eu/db/ithaphen) of ITHANET portal.²

Methods: Herein, we collect and curate more than 4400 cases associated with haemoglobinopathies. Case-level data are extracted from publications as weel as from unpublished anonymous cases from direct submission to ITHANET portal.

Results: IthaPhen, a searchable and intuitive database of public anonymised case reports linked to haemoglobinopathies. IthaPhen integrates genotypic data with haematological, biochemical, histological, and clinical data and, through search queries of user-defined genotypes, returns both the primary case level data and aggregated, visualised reports.

Summary/Conclusion: Based on expert curation of published and contributed data, IthaPhen serves audiences with an interest in haemoglobinopathies, across research and health care, by facilitating genotype-phenotype correlation and interpretation of globin gene variants.

Topic: 003–Clinical and epidemiological studies

T.M. Venou¹, F. Kyriakidis², F. Barmpageorgopoulou², S. Theodoridou³, A. Vyzantiadis³, P. Klonizakis¹, E. Gavriilaki⁴, E. Vlachaki¹

Adult Thalassemia Unit, 2nd Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital¹, Department of Medicine, School of Health Sciences, Aristotle University of Thessaloniki², Hemoglobinopathies prevention unit, Hippokration General Hospital³, 2nd Propedeutical Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital⁴

Background: B-thalassemia is the most common genetic blood disorder characterized by reduced production or complete absence of β-globin chains. Endocrine abnormalities correlated with β-thalassemia are primarily associated with iron overload, chronic anaemia, and hypoxia.

Aims: The present study aimed to investigate the frequency and factors contributing to the development of glucose metabolism disturbances in patients with transfusion-dependent β-thalassemia (TDT). We also investigated the relationship of pancreatic iron overload with other iron overload biomarkers.

Methods: We consecutively investigated two groups of patients with TDT at the Adult Thalassemia Unit, B Department of Internal Medicine, Hippokration General Hospital (2018–2022). The participants were segmented into different groups based on their glucose metabolism impairment status [Group 1: patients without diabetes mellitus or impaired glucose tolerance, 46/64 (71.9%), Group 2: patients with diabetes mellitus or impaired glucose tolerance, 18/64 (28.1%)]. We compared both groups regarding factors that can contribute to the occurrence of impaired glucose metabolism. Moreover, results from laboratory tests retrieved from the patients past medical history were recorded and analyzed. The diagnosis of type 2 diabetes mellitus (DM) was determined according to the American Diabetes Association guidelines (fasting plasma glucose >126 mg/dL or 120-minute glucose >200 mg/dL). The diagnosis of impaired glucose tolerance was based on the Oral Glucose Tolerance Test (OGTT) (120-minute glucose). We also performed a multivariate logistic regression analysis to investigate the impact of each of the independent investigated variables on the development of impaired glucose metabolism. In a subset of patients with transfusion-dependent β- thalassemia on iron chelation therapy, we investigated the association between pancreatic iron overload (T2* MRI) and liver and heart overload (T2* MRI) as well as serum glucose and ferritin levels.

Results: Impaired glucose metabolism was significantly correlated with age serum GGT levels (p:0.02 and p:0.02, respectively). No statistically significant difference was found between the two groups regarding the remaining investigated parameters (p > 0.05). Regarding the use of drugs which can lead to impaired glucose metabolism, b-blocker administration was significantly correlated with the development of glucose metabolism disturbances (p:0.02). According to the results of the multivariate regression analysis, none of the investigated variables were found to have a significant impact on the development of glucose metabolism disturbances when other predictors were held constant (p > 0.05). A statistically significant relationship between pancreatic and heart MRI T2* (Pearson's coefficient: 0.45, p:0.04) indicates a positive linear relationship between those two variables.

Summary/Conclusion: Elevated GGT levels in patients suggest that oxidative stress plays a vital role in the development of DM. In patients with TDT, pancreas MRI T2* can be a useful tool in predicting heart iron overload. However, more research is needed to determine the various factors involved in the development of glucose metabolism disturbances in patients with TDT and to identify reliable biomarkers that can predict glucose regulation.

Topic: 003–Clinical and epidemiological studies

N.M. Archer¹, C. Stephanou², M. Xenophontos², L. Tshilolo³, F. Nzengu³, S. Fazili³, O.E. Nnodu⁴, M.M. Nwegbu⁴, A.D. Waziri⁵, S. Awwalu⁵, S. Christou⁶, I. Savvidou⁶, A. Rekleiti⁶, A. Minaidou², M.D. Diamantidis⁷, N.Y. Mohd Yasin⁸, N.A. Abdul Aziz⁹, V.S. Selvaratnam¹⁰, E.E. Esa⁸, A. Glenthøj¹¹, S. Delicou¹², L.G. Dogara¹³, M.N. Dimopoulou¹⁴, R.Z.A. Raja Sabudin¹⁵, N. Jalil¹⁶, C.K. Loh¹⁷, S.C.D. Lau¹⁷, B.A. Zilfalil¹⁸, M. Norsarwany¹⁸, S. Syahiran¹⁸, Z.A. Ahmad Fikri¹⁸, H.F. Hashim¹⁸, M. Oni¹, A. Lukangu¹⁹, L. Alves¹⁹, M. Brito²⁰, V. Giannuzzi²¹, F. Bonifazi²¹, K. Michailidou², S. Chatzimatthaiou², C.W. Lederer², P. Kountouris²

Dana-Farber/Boston Children's Cancer and Blood Disorders Center¹, The Cyprus Institute of Neurology & Genetics², CEFA-Monkole Institut de Recherche Biomédicale³, Centre of Excellence for Sickle Cell Disease Research and Training, University of Abuja⁴, Ahmadu Bello University Teaching Hospital⁵, Thalassemia Centre, Archbishop Makarios III Hospital⁶, General Hospital of Larissa⁷, Haematology Unit, Cancer Research Centre, National Institutes of Health⁸, Department of Haematology, Hospital Sultanah Bahiyah⁹, Department of Haematology, Hospital Ampang¹⁰, Danish Red Blood Cell Center, Department of Hematology, Copenhagen University Hospital - Rigshospitalet¹¹, Hippokrateio Hospital of Athens¹², Kaduna State University¹³, Laikon General Hospital of Athens¹⁴, Department of Pathology, Faculty of Medicine, UKM Medical Centre, UKM¹⁵, Department of Laboratory Diagnostics Services, UKM Specialist Children's Hospital, UKM¹⁶, Department of Paediatrics, UKM Specialist Children's Hospital, UKM¹⁷, School of Medical Sciences, Universiti Sains Malaysia¹⁸, Maternidade Lucrécia Paim¹⁹, Escola Superior de tecnologia da Saúde de Lisboa, Instituto Politécnico de Lisboa²⁰, Fondazione per la Ricerca Farmacologica Gianni Benzi Onlus²¹

Background: Hemoglobinopathies, including sickle cell disease (SCD) and thalassemia syndromes, represent the commonest monogenic diseases in the world. Although their pathogenesis is well established, the diverse clinical manifestations and the varying degree of severity of hemoglobinopathies are less understood and are partly influenced by genetic modifiers. Despite the identification and characterization of several genetic modifiers by previous studies, these are, as yet, insufficient to guide treatment recommendations or stratify patients reliably. The International Hemoglobinopathy Research Network (INHERENT) will investigate the role of genetic modifiers in hemoglobinopathies, through a large, multi-ethnic genome-wide association study (GWAS), with the aim to identify and validate further disease modifiers that can be used for patient stratification and personalized treatment.

Aims: This pilot study aims to test the operational feasibility of the INHERENT study across different geographic and healthcare settings and, thus, identify and address challenges in performing the envisioned GWAS within INHERENT.

Methods: INHERENT members participating in the pilot study have been selected based on their geographic location, disease group distribution (SCD/thalassemia) and hemoglobinopathy-specific healthcare policies. Written informed consent was collected by all patients before participating in the study. The following steps of the study implementation have been tested: (a) obtaining local bioethics approval on the basis of the applicable local legal framework, (b) patient enrollment and data collection using a common case report form (CRF), (c) sample collection and shipment, (d) genotyping of globin genes, (e) centralized GWAS experiments, and (f) statistical analysis. The completeness of the collected dataset was also assessed.

Results: The pilot study enrolled 734 patients from 14 centres spanning 8 countries, namely Angola, Cyprus, Denmark, DR Congo, Greece (3), Malaysia (3), Nigeria (3), and the USA. Additional twelve centres have obtained a bioethics approval, but have not initiated patient enrolment yet.

The distribution by disease group is 53.5% SCD and 38.1% thalassemia patients, while the median age is 22 years (mean: 25.3), with 55.6% adult and 29.7% pediatric patients, with the remaining records being incomplete for age and disease.

Data completeness (affirming presence, absence, or not enough data) of key parameters related to medical complications is approximately 80%, while the range of completeness for laboratory parameters was wide, with a maximum at 70%. Figure 1 illustrates the percentage of patients with at least one medical complication per category by hemoglobinopathy and age group. Notably, a higher rate of cardiac/pulmonary, kidney/liver, endocrinological and bone complications is observed in adult thalassemia patients, while a higher rate of pain-related and acute anemia complications are observed in pediatric SCD patients.

Biological material for 552 of the patients was shared centrally, and GWAS experiments have been performed using the Illumina GSA SNP array.

Key challenges identified in the pilot study include: the unavailability of key phenotypic data in routine clinical practice in several countries, particularly when the tests are not covered by insurance. This affects the completeness of the dataset as well as the cost associated with the conduct of a large scale study like INHERENT.

The unavailability of laboratory data at the time of diagnosis, particularly for adult patients, due to the lack of electronic health records in many centres.

The need for a more detailed standardisation and simplification of the INHERENT CRF to ensure uniform and consistent collection of data across participating centres.

The unavailabity, limited access, or high costs for molecular diagnostic services in some countries.

Challenges related to the storage, quality and shipping of biological material in some countries have been identified and addressed during the study.

Summary/Conclusion: The INHERENT pilot study tested common standards developed within INHERENT and enabled early identification of key challenges associated with the execution of a large, multi-ethnic study for hemoglobinopathies. The pilot is pivotal for scaling up the INHERENT GWAS across the entire network membership, enabling the study of a hemoglobinopathy population of unprecedented size and diversity. This will facilitate novel discoveries and deepen our understanding of the underlying genetics, thereby paving the way for advanced personalized treatments and diagnosis.

Topic: 003–Clinical and epidemiological studies

L. Ocello¹, F. Pavan², G.M. Ferrari³, A. Biondi⁴, V. Baldini⁵, P.C. Corti³

Università degli Studi di Milano-Bicocca¹, Anestesia e Rianimazione, Fondazione IRCCS San Gerardo dei Tintori², Ematologia Pediatrica, Fondazione IRCCS San Gerardo dei Tintori³, Dipartimento di Medicina e Chirurgia, Università degli Studi Milano-Bicocca⁴, Servizio Immunotrasfusionale, Unità Semplice di Aferesi, Fondazione IRCCS San Gerardo dei Tintori⁵

Background: Red cell exchange (EEX) is a relevant procedure for the management of severe sickle cell (SC) disease: it can alleviate or solve complications in acute cases and prevent their development in chronic cases. The reduction of the hemoglobin S (HbS) level below 30% can be obtained with repeated manual procedures or automated EEX (aEEX): this procedure is an isovolemic red cell exchange and can lower HbS to a predefined level with limited iron overload. However, aEEX requires specialized equipment and trained staff; moreover, it can be limited in childhood by the patient's age, weight and venous heritage.

Aims: The aim of this monocentric observational study is to demonstrate the successful implementation of ultrasound-guided peripheral intravenous access (IA) to perform aEEX in the pediatric SC population in our pediatric hematology center.

Methods: As of 2018, we have introduced a multidisciplinary vascular access team (pediatric hematologist, anesthesiologist and nurse) able to perform ultrasound-guided peripheral and central intravenous accesses for aEEX.

Results: From May 2018 to June 2024, we performed 96 aEEX (75 in the context of chronic transfusion therapy, 21 for acute complications) in 21 SC children and adolescents: the median age was 15.8 years old (13.5–17.8; min 3.1–max 20.9). The main indications were recurrent vaso-occlusive disease (VOC) (71/96, 75.5%), cerebral vasculopathy (10/96, 10.6%) and VOC prevention before surgery (10/96, 10.6%). In 66/96 procedures, a US-guided peripheral IA was used, with light oral sedation during the placement procedure due to the age of the children or the anxiety state of the adolescent patients. In 30/96 procedures, a US-guided central IA (26 femoral intravenous central catheter or FICC, 3 central intravenous central catheter or CICC, 1 peripherally intravenous central catheter or PICC) was used, with deep intravenous sedation. In 9/66 (13.6%) procedures (2 central IA, 7 peripheral IA), temporary failure of vascular access was noted without affecting the outcome of therapeutic apheresis in terms of reduced HbS at the end of aEEX. A total of 94/96 EEX were completed, with a good patient outcome and a median HbS after EEX of 27.5% (22.8–34.0). The median duration of EEX was 74.0 min (59.0–90.0), with a non-significant difference between central IA (73, 62.8–97.5) and peripheric IA (77.0, 59.0–87.0). In one case the procedure was interrupted due to an unstable peripheral IA; in another case, the exchange with a FICC was unsuccessful, with a post-procedure HbS similar to the starting value (probable improper position of the tip of the catheter during blood exchange). No infections or thrombosis have been observed during or after the procedures.

Summary: A median HbS value after aEEX <30% was achieved in both peripheral IA and central IA procedures, although a higher number of minor complications (transient failure) occurred in aEEX with peripheral IA. In addition, a less invasive procedure for peripheral IA placement, with light sedation and a comparable duration of the procedure, appears to be safer and better tolerated by pediatric patients.

Conclusion: In conclusion, the introduction of a multidisciplinary vascular access team has changed the therapeutic options for SC patients at our center. In particular, the outpatient placement of a US-guided peripheral IA, a simple, well-tolerated and low-risk procedure, comparing with central IA, makes aEEX possible in pediatric patients who in the past could only undergo repeated manual exchange.

Topic: 003–Clinical and epidemiological studies

J.J. John James¹, B.A. Biree Andemariam², J.M. Johnny Mahlangu³, R.C. Raffaella Colombatti⁴, J.W. John Waller⁵, S.A. Samar Al-Behaisi⁵, G.M. Gareth Morrell⁶, C.T. Cassandra Trimnell⁷

Sickle Cell Society¹, University of Connecticut Health², University of the Witwatersrand³, University of Padova⁴, Novo Nordisk Health Care AG⁵, Madano⁶, Sickle Cell 101⁷

The LISTEN Survey was fully funded by Novo Nordisk. Novo Nordisk employees input into the survey design and content and are co-authors of this abstract.

Background: Real-world data describing attitudes of people with sickle cell disease (PwSCD) to clinical trial (CT) participation are limited. The Learnings and Insights into Sickle Cell Trial Experiences (LISTEN) Survey assessed PwSCD's motivators and barriers to participation in CTs and identified that improving access and recruitment requires clear communication of potential benefits and anticipated safety profile.¹

Aims: Identify archetypes of PwSCD from the LISTEN Survey with similar attitudes regarding CT participation, which may tailor future recruitment strategies.

Methods: From October 2022 to June 2023, a diverse group of adults (≥18 years) with SCD in 17 countries globally completed a quantitative survey. PwSCD rated the likelihood of taking part in a CT for SCD on a 5-point scale (very unlikely to very likely). PwSCD rated the importance of specified factors (in five categories) that drive the decision to participate in a CT for SCD on a 7-point scale (not at all to extremely important) or ranked them (most to least important). We used hierarchical cluster analysis to group PwSCD who rated/ranked factors similarly into distinct archetypes, and chi-squared tests to assess differences across the archetypes. Data are reported for the proportion of PwSCD who ranked factors as one of the two most important in a category or rated them extremely/very important.

Results: Overall, 1145 PwSCD (58% female) with a median age (interquartile range) of 30 years (24–38) completed the LISTEN Survey. Of these, 86% were grouped into one of five archetypes (14% were not clearly defined): treatment-motivated (22%), practical-minded (14%), care-motivated (6%), uncertain (23%) and risk-averse (20%) (Figure). For each archetype, the proportion who were very likely/likely to join a CT for SCD was 59%, 65%, 64%, 47%, and 50%, respectively. Treatment-motivated PwSCD ranked the opportunity to try a new treatment that might work better (93%) as most important. Practical-minded PwSCD ranked the potential to better manage their symptoms (88%) as most important but were concerned about some practical barriers such as missing work/school (46%), additional effort/planning to start the trial treatment (40%) and additional travel requirements (42%). Care-motivated PwSCD ranked the possibility of receiving the trial treatment regularly once the trial ends (94%) and access to SCD specialists (66%) as most important. An important barrier for risk-averse PwSCD was that the trial treatment might have different side effects than they currently experience (87%), whereas, for PwSCD in the uncertain archetype, important barriers also included missing school/work (66%) and that trial treatment might not be as good as their current treatment (66%). Supporting treatments that may benefit other PwSCD was important for most archetypes.

Summary/Conclusion: In a time of opportunities for individualised treatment for PwSCD, differences in motivators and barriers to CT participation should be considered. Tailored communications from healthcare professionals, industry and patient organisations, which account for differing attitudes among PwSCD, may improve recruitment and increase diversity of CT populations. Results from this global survey could support future development of a tool for discussing CTs with potential participants.

1. J James et al. Blood, 2023; 142(Suppl 1), 2498.

This abstract was accepted and presented at the EHA Annual Congress, 13–16 June 2024, Madrid, Spain; Abstract S331.

Topic: 003–Clinical and epidemiological studies

N.Y. Situmorang¹, E. Divina¹, L.D. Rahmartani², T.T. Sari², P.A. Wahidiyat²

Faculty of Medicine, Universitas Indonesia¹, Pediatric Department, Dr Cipto Mangunkusumo National Referral Hospital²

Background: Transfusion-dependent thalassemia (TDT) is a term for thalassemia patients with severe manifestations that need regular blood transfusion to eliminate anemia complications and compensatory bone marrow expansion. However, it leads to iron overload causing various organ dysfunctions, added with chronic hypoxic state from anemia and toxicity due to chelating drugs, some studies have observed brain dysfunction in TDT patients. With the improvement of treatments and increased survival rate for these patients, evaluation of cognitive function from a young age is important for their future and the Wechsler Intelligence Scale for Children (WISC) was seen as helpful in determining it.

Aim: To compare studies evaluating cognitive impairment in pediatric TDT patients and the possible confounding factors.

Methods: A systematic review was conducted using five databases (MEDLINE, EMBASE, Scopus, Proquest, Cochrane) and individual search on 28 March 2024. All original articles were searched with keywords: Transfusion-dependent thalassemia patient or thalassemia major, cognitive impairment or IQ, and iron. This review included those that study pediatric patients and the effects on their cognitive level using WISC while excluding those with traumatic brain injury or comorbidities on the brain. Quality assessment was done using NHLBI for cross-sectional studies and CASP for other study types.

Results: After removing duplicates, we obtained 72 articles from databases and individual searches. After undergoing abstract and full-text screening, this study discusses 10 articles. All studies used full-scale IQ domains and/or WISC as outcomes and the combined mean values of Total IQ (TIQ) were 89.781 ± 3.635 (low-average). Of the 10 studies, only six measured Verbal IQ (VIQ) and Performance IQ (PIQ). We calculated the VIQ and PIQ combined mean values and found 96.615 ± 4.689 (average) and 90.03 ± 4.642 (average) respectively in TDT patients. Meta-analysis of 7 studies comparing TDT children and normal children found that TDT children have lower cognitive performance with a highly significant difference (χ² = 84.750, df = 14, p < 0.001). With meta-analysis, we also found that age has combined significant negative correlation with TIQ (r = −0.211; p-value 0.008) and age of diagnosis has combined significant negative correlation with PIQ (r = −0.250; p-value 0.002). No significant combined effect is found for iron/ferritin levels with either TIQ (r = −0.076; p-value 0.226), VIQ (r = 0.050; p-value 0.427), and PIQ (r = −0.120; p-value 0.057). Meta-analysis could not be done for other confounding factors (gender, compliance with chelation therapy, pre-transfusion hemoglobin) due to limited studies.

Table 1. Cognitive function (TIQ, VIQ, PIQ) and significant confounding factors from included studies.

Summary/Conclusion: This is the first systematic review and meta-analysis to find factors correlating to the cognitive performance of TDT children. We found that TDT patients have low average cognitive performance. Age and age of diagnosis are found to negatively correlate with patients' cognitive performance.

Topic: 003–Clinical and epidemiological studies

B.K.G. Goswami¹

North Bengal Medical College and Hospital¹

Background: Hb-E Hemoglobiopathies (β-26Glutamic Acid Lysine) are found to be most common form of Hemoglobinopathy-Thalassemia Disorders in many countries of South-East Asia including India. A high frequency of different β-thalassemia (BT) alleles in these populations results in birth of Hb-E-β thalassemia, very frequently.

The northern part of the state of West Bengal, India is home to a number of indigenous population groups. The most widely distributed among them is the Rajbanshi. The Rajbanshis constitute the largest percentage and number of the Schedule Caste population in West Bengal (18.40% and nearly 3.4 lacs, respectively).

HbE-Hemoglobinopathies can present as trait, clinically asymptomatic, homozygous state with mild pallor and double heterozygous state with other Hb variants and Thalassemias. Among them the most common trait is Hb-E-β-thalassemia, which presents like Transfusion dependent Thalassemias. In fact, this has been studied that, this Hb-E-β-thalassemia, are responsible for highest number of case of Transfusion dependent Thalassemia in West Bengal. Other uncommon double heterozygous state include Hb-SE, Hb-DE, and with α-thalassaemias.

The Basic pathogenesis are very close to β-thalassemias, with Ineffective erythropoiesis, along with more apoptosis and oxidative damage lead to shortened red cell survival, thereby hemolysis and consequences. This is frequently observed that persons with Hb-E Hemoglobinopathies are usually asymptomatic, but in febrile state due to any insult, they can present with marked hemolysis (Rees et al., 1998). Hb-E Hemoglobinopathies, also known as Thlassemic Hemoglobinopathies as this is thought that there is reduced synthesis of β-chain is due to activation of a cryptic splice site, leading to abnormal messenger RNA processing, which is non-functional (Orkin et al., 1982).

As Hb-E Hemoglobinopathies essentially involving β-chain, both functionally and structurally, persons present with microcytic and hypochromic RBCS with low MCV and MCH. As a whole Iron deficiency Anemia (IDA) is considered to be a major public health problem, in one hand, Iron needs to be supplemented during antenatal period, while, on other hand, person with Hb-E may present with hemolysis, resulting in Iron accumulation. As this Hb-E Hemoglobinopathies with microcytic and hypochromic RBCs are among the predominant population of this region, it can pose some problems to the general practitioners regarding planning of their treatment strategies. And hence need awareness among health care workers

Aim: This presentation aims to highlight the impact of Hb-E Hemoglobinopathies in screening and Health care activities.

Method: Compilation of Last 5 year data after screening for Hemoglobinopathies by CE-HPLC method and other methods for study of hemoglobin variants as and when needed, including CBC from Hematology analyzer in Thalassemia Control Unit, Department of Pathology, North Bengal Medical College.

Results: Following points have been isolated as major impact to be discussed. Magnitude of Burden of Hb-E Hemoglobinopathies on the Population of Northern district of Bengal, with high occurrence among some specific population groups including Rajbangshi, prevalent at Northern districts of West Bengal, India.

Varied presentations due to genetic variation, leading to problem in interpretation of many chromatogram of CE-HPLC, now a days considered to be gold standard in screening for Thalassemia and Hemoglobinopathies.

Both β-thalassemia trait (BTT) and Hb-E Hemoglobiopathies trait (ET) are clinically silent. If they are not screened before marriage, the chance of birth of E-β-thalassemia baby is high, which simulate the clinical features of Beta Thalassemia Intermediate or the transfusion-dependent β-Thal. major

Occurrence of Hb E hemoglobinopathies even among the non-anemic persons is not uncommon, making it more important in screening.

High prevalence of Hb-E Hemoglobiopathies in the local population also possesses problems in evaluation of microcytic hypochromic anemias, the morphology also observed in Iron Deficiency Anemia, still now considered to be the commonest cause of anemia, especially in antenatal mothers.

Association with co-morbid states and change in course of disease (due to poorly understood pathogenetic mechanism of Hb-E) as sometimes observed in some cases with Hb-E Hemoglobinopathies, which requires a thorough research

As the presence of variant hemoglobin interferes with the interpretation of glycated hemoglobin (HbA1c), the manufacturers of Instruments for HbA1c determination by HPLC require more research and development.

Summery/Conclusion: Hb-E-Hemoglobinopathies, though considered to be clinically not so significant, can pose problems with its varied presentations, Awereness among health care workers about its clinical presentation, blood picture, Diagnosis and fate is of paramount importnace in this zone.

Topic: 003–Clinical and epidemiological studies

C.E. Carlos Escobar¹, M.M. Marta Moniz¹, M.M. Maria Mendes¹, C.A. Catarina Amorim¹, F.C. Francisca Costa¹, C.A. Clara Abadesso¹, H.A. Helena Almeida¹, P.N. Pedro Nunes¹

Hospital Fernando Fonseca, Unidade Local de Saúde Amadora e Sintra¹

Introduction: Red blood cell exchange (RBCX) is a therapeutic procedure used to prevent complications in patients with sickle cell disease (SCD). However, the limited availability of packed red blood cells (PRBC) poses a significant challenge to the widespread implementation of this treatment. Isovolemic hemodilution (IHD-RBCX) allows for an efficient decrease of HbS while saving donor's RBC. However, data on IHD-RBCX use in children is scarce. We aim to describe our experience with the use of IHD-RBCX with Spectra Optiaâ Apheresis System in a pediatric population with SCD, with a focus on feasibility and RBC savings.

Methods: Pediatric patients who underwent IHD-RBCX over a 42 months period (September 2017 to March 2021) were retrospectively analyzed. PRBC savings with hemodilution were determined comparing the RBC volume used in this protocol and compared to the theoretical volume of RBC needed without depletion to achieve the same FCR (fraction of cells remaining), conducted using the RBCX Calculation Tool App – Terumo BCT®. To confirm the efficiency of this protocol we compared the difference between the post-procedure hematocrit (Htc) and targeted final Htc and the HbS (%) at the end of the procedure.

Results: 108 depletion/exchange (D/E) procedures were performed on 16 patients (mean age 16.5 ± 2.1). Mean pre-procedure Htc was 27.9% and it was reduced to a mean target Htc post-hemodilution of 23.5%, with a decrease between 1.5% and 8.6% (mean: 4.4% ± 1.4%). The protocol appeared to be safe as no adverse effects with clinical repercussion during the hemodilution phase occurred. Mean blood consumption of packed RBC (PRBC) per procedure was 1411.3 ± 249.1 mL with a total of 152,416 mL. To achieve an equivalent final FCR through only exchange procedure as opposed to D/E, an additional 11,791 mL of red blood cells would be required, representing a 7.2% increase. A mean volume 179.4 ± 74.4 mL of saline fluid was used in each procedure (range: 28–372 mL). The post-procedure Htc and target HbS reached expected values.

Conclusion: IHD-RBCX in children with SCD has shown that the procedure is safe and well tolerated, and that it can be used in the pediatric population since the requirements for a high hematocrit and clinical stability are met. Isovolemic hemodilution red blood cell exchange (IHD-RBCX) should be employed also in young SCD patients to conserve the scarce resource of donor packed red blood cells (PRBC).

1. E Merlin et al. Transfusion and Apheresis Science, 2019; 58(2), 136–141.

Topic: 003–Clinical and epidemiological studies

N. Scaramellini¹, A. Marchetti², E. Sambruna², G. Aquilino², F. Ballardini², G. Gazzola², E. Cassinerio³, V.M.E. Di Stefano³, D. Maira³, M. Ferraresi³, D.L. Panzieri³, S. Leoni³, C. Curcio⁴, M.A. Irrera⁴, G. Graziadei³, M. Migone De Amicis³, C. Cesaretti⁵, I. Motta¹

Dipartimento di Scienze Cliniche e di Comunità, IRCCS Fondazione Ca' Granda, Policlinico di Milano¹, University of Milan, Milan, Italy², Medicina ad Indirizzo Metabolico, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan³, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, SC Patologia Clinica, Settore Genetica Medica, Milano, Italy⁴, Unità di Genetica Medica, Dipartimento Materno Infantile, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milan, Italy⁵

Background: Hemoglobinopathies are genetic disorders caused by mutations in the genes encoding globin chains. These conditions are the most common monogenic disorders worldwide, resulting in significant morbidity and mortality among those affected by the most severe forms. Antenatal evaluation for thalassemia and sickle cell disease (SCD) enables couples to know their reproductive risk, thus allowing an informed reproductive choice.

Aims: We herein describe the characteristics of couples referred to our tertiary referral center in Milan, Italy, for evaluation of hemoglobinopathy risk and their management.

Methods: We retrospectively collected and analyzed couples' data referred to our center from the 1st of July 2021 to the 31st of December 2022.

Results: Three hundred and fifty-one couples were evaluated: the median age was 34 years, with a tendency for younger age in female partners; 67% (234/351) of the women were already pregnant at the time of evaluation (median gestational age 18 weeks, range 7–37), while 33% (117/351) were referred for preconception counseling. Individuals from more than 48 different countries were screened, and the most represented countries of origin included: Italy (50%), Nigeria (6%), Bangladesh (4%), and Ivory Coast (4%), underpinning a vastly diverse genomic background.

The referral was triggered by evidence of microcytic anemia (58%) or HPLC abnormalities (42%), including Hb variants, HbA2 abnormalities, or elevated HbF in at least one partner. After re-evaluation of all subjects with HPLC we found 101 subjects HbS carriers, 15 HbC carriers, and 307 subjects with an HPLC suggestive of the beta trait, which was confirmed in 102 subjects by the beta globin molecular gene.

In fact, considering all the couples, 45% (158/351) underwent advanced molecular tests to determine the nature of the Hb defect, guided by the results of the first level panel. Among these, 33 couples (12% of the total) were found to be at risk for transmission of severe clinical forms of B-thalassemia, sickle cell anemia, or compound ß-disorder heterozygosity (HbS/B-thal, HbC/HbS). One additional couple (0.4%) was at risk for HbH disease. In addition, 4 couples (1.5%) were found to be at risk for thalassemia intermedia combining a ß-thalassemia mutation and a-gene triplication. Of the above, all 34 couples underwent invasive fetal evaluation: 24 women underwent chorionic villous sampling, while 10 received amniocentesis. A diagnosis of thalassemia in the fetus was reported in 6/34 (18%) cases and 3 (9%) of SCD. Interestingly, during the 18 months of observation, among the evaluated adult subjects, we found 4 cases of non-transfusion dependent thalassemia (NTDT) and 1 of HbS/β-thal in otherwise healthy subjects. All 4 cases of NTDT resulted from a-gene triplication paired with a β-thalassemia heterozygous defect. Furthermore, a triplication was found alone in 4 subjects without additional Hb gene defects. Overall, a triplication was detected in 9 out of 154 (5.8%) individuals who underwent HBA gene analysis.

Summary: The median gestational age at presentation was high, leading to a limited time for couples to receive the appropriate counseling to make an informed reproductive choice. Increasing awareness across all involved specialists remains the mainstay for an effective prevention program to promptly identify at-risk couples and offer counseling at the right time.

Interestingly, the prevalence of the HbS trait was similar to the beta-trait, the latter known to be endemic in Italy. This suggests that epidemiology is changing, and it is mandatory for physicians to be aware of the distribution of HbS, especially considering that complete blood count can be silent, differently from beta-trait carrier

1. D Venturelli et al. Blood Transfusion, 2014; 12, 346–351.

2. J Traeger-Synodinos et al. European Journal of Human Genetics, 2015; 23(4), 426–437.

3. K Ryan et al. British Journal of Haematology, 2010; 149(1), 35–49.

Topic: 003–Clinical and epidemiological studies

L.W.M. Wakhu¹, F.J.K. Kirkham², S.H. Hamdule²

Strathmore University¹, University College London²

Background: Hydroxyurea is a drug with evidence of efficacy in sickle cell disease (SCD), but there are few data in Africa. Infection, bacterial and malaria, is widely considered to be one of the major causes of illness and death in patients living with SCD in Africa. It would be desirable if hydroxyurea lowered infection risk as well as reduced SCD morbidity.

This review was registered on the PROSPERO database (CRD42024525869) and has been conducted within the African Research and Innovative Initiative for Sickle Cell Education (ARISE), which has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 824021.

Objectives: To review randomised controlled trials (RCTs) conducted in Africa to assess the safety of hydroxyurea in SCD: malaria infections, non-malaria infections, low haemoglobin, low white cell count, and low platelets.

To review RCTs conducted in Africa to assess the effectiveness of hydroxyurea in SCD: reduction in death, hospitalisation, stroke; patient-reported adverse outcomes, e.g., pain, transcranial Doppler velocity; increase in haemoglobin, haemoglobin F%, mean cell volume (MCV).

Methods: Two reviewers (L.W. and F.K.) independently ran advanced searches on six databases: Embase, Medline, Scopus, Web of Science, PubMed, and PsycINFO. The MeSH terms “sickle cell disease” or “sickle cell anaemia” were paired with “hydroxyurea” or “hydroxycarbamide” and “randomised trials” or “randomized trials.” Any discrepancies arising were resolved by consensus. Articles published from any time point until February 2024 were included in the review, followed by a re-run of searches in March 2024. There were no restrictions on the age of the participants. All randomised placebo-controlled, dose-controlled trials of hydroxyurea (HU) therapy for SCD in Africa were included, while case-control, cohort and cross-sectional studies, single cases, editorials, and reviews were excluded. This systematic review was conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and was registered in PROSPERO. Two reviewers independently used the Cochrane risk-of-bias tool for randomised trials (RoB 2) version 2 to assess trial quality.

Results: Overall, 4 RCTs (1–4) were included in the systematic review. Three reported on malaria; there was no evidence that hydroxyurea therapy increased the risk of malaria (Figure 1). In one study, there were no significant differences in non-malaria infection rates in moderate dose HU compared with placebo (Figure 2). There was a significantly lower rate of hospitalisation due to VOC (acute pain or acute chest syndrome) in moderate-dose hydroxyurea therapy than in low-dose therapy, most of which occurred at home rather than in the hospital.3 Significantly lower rates of VOC pain were seen in children aged 0–3.99 years receiving 20 mg/kg than placebo. Children aged 3–6 years receiving the maximum tolerated dose had a significantly lower incidence of VOC pain than those receiving 20 mg/kg (Figure 3).²

Low haemoglobin count (<6.0 g/dL) occurred less frequently in the hydroxyurea group than in the placebo group, with much less variation in neutropenia, thrombocytopenia, and reticulocytopenia between the two groups. Hydroxyurea therapy resulted in a significant increase in haemoglobin, MCV, and fetal haemoglobin (HbF) compared to placebo. Hydroxyurea led to a significant decrease in the white blood cell count, absolute neutrophil counts, and platelets, which was not observed in the placebo group. The levels of fetal haemoglobin were higher in the moderate-dose arm than in the low-dose arm (Figures 4–7). All RCTs had a low risk of bias, were well-designed, and were of good quality.

Conclusions: HU is the only FDA-approved SCD drug widely available in Africa. Despite not having any age restrictions in the searches, the 4 trials that were included in the review only focused on children. There is a gap in high-quality research and evidence on the use of hydroxyurea in SCD in Africa, particularly in adults, perhaps due to the lack of Pharma interest and inadequate funding. Nevertheless, these trials were as a result, they may offer a preliminary picture of hydroxyurea therapy and the current gaps in Africa. No patient experienced bone marrow suppression, even at doses higher than 20 mg/kg, implying that hydroxyurea does not cause significant bone marrow toxicity under controlled conditions. Dose escalation may confer additional clinical benefits, but due to limited facilities to monitor toxicity, administering a higher dose may become a treatment barrier do might be reserved for those with no reduction in the pain crisis or blood transfusion requirement.

Topic: 003–Clinical and epidemiological studies

A. Lai¹, K.Z. Summers¹, O. Agrippa¹, M. Yusuf¹, R. Dacosta¹, K.A. Anie², P. Telfer³, S. Lugthart⁴

Sanius Health¹, London North West University Healthcare NHS Trust², Barts Health NHS Trust³, University Hospitals Bristol and Weston NHS Foundation Trust⁴

Background: Sickle cell disease (SCD) is the most common genetic blood disorder, affecting 1 in 4600 people in the UK and 1 in 5000 people in the US. These patients often experience vaso-occlusive crises (VOCs), which are acute pain episodes caused by the aggregation of abnormal sickled red blood cells and adherent blood cells, leading to vaso-occlusion and potential end-organ damage. Beyond clinical burdens such as acute infections, chronic lung, and cardiovascular diseases, patients who experience recurrent VOCs incur high annual and lifetime healthcare costs, resulting in a significant economic burden.

Aims: To gain insights into real-world patient experiences, focusing on understanding the early prodromal signs, symptoms, and timeline of VOCs.

Methods: Data collection involved two cohorts: a UK cohort comprising 9 patients who reported frequent VOCs (defined as 3 or more self-reported VOCs) during a virtual workshop, and a US cohort with 58 patient responses collected through a survey conducted between February and April 2024. Both the workshop and the survey have been designed to capture detailed patient experiences with VOCs, with a focus on key causes, associated signs and symptoms, typical build-up period and recovery time.

Results: For the US cohort (n = 58), the main causes of VOC were identified as stress (52%), infection/illness (34%) and weather changes (27%). Similarly, for the UK cohort (n = 9), the primary causes were stress (100%), fatigue (44%) and weather changes (33%). Early prodromal signs, symptoms and triggers were compared between the cohorts (Figure 1), highlighting slight variations in specific indicators. In the US cohort, this included physical overexertion (41%), weather change (27%), pain (28%), difficulty in breathing (22%), fatigue (22%) and stress (22%). In the UK cohort, the most common early prodromal signs and symptoms included stress (100%), pain (89%), fatigue (44%), weather changes (33%), physical overexertion (22%), and yellow eyes (22%).

A comparison of pain locations was made between the cohorts, revealing mostly similar patterns. US patients most frequently reported pain in the back (50%), legs (34%), chest (21%) and arms (21%). In the UK cohort, the top three pain locations were the back (44%), chest (33%) and hip (22%).

The duration and recovery time of VOCs varied in both cohorts, depending on severity. In the US cohort, the most common duration and recovery time were 1–2 weeks (25% and 28%, respectively). In the UK cohort, the most frequent VOC duration was slightly shorter, at 5–7 days (33%), with additional reports of 1–3 days (22%) and up to 1 day (11%). The UK patient cohort reported varied recovery times (11%), with some recovering within a few days (22%), 1–2 weeks (11%), and 2–3 weeks (11%).

Summary/Conclusions: In both geographical patient cohorts, stress and weather changes were the leading causes of VOCs, with the most frequently observed early signs and symptoms including stress, pain, fatigue, and physical exertion. Patients in both cohorts consistently reported pain in similar locations, primarily in the back, legs, and chest. The impact of these crises can last for weeks or even months depending on their severity, significantly affecting patients' daily lives.

To predict VOCs for these patients, understanding the physiological metrics such as heart rate, body temperature and sleep quality linked to these early signs and symptoms in different patient cohorts is key. This work highlights the importance of tracking and monitoring these metrics across different patient cohorts, to implement targeted prevention and support services. This will prevent the onset of VOCs and hospitalisation, reducing burdens on patients and the healthcare system, and optimising SCD management with improved patient outcomes.

However, a limitation of this data comparison was the small cohort size and variations in data collection methods. To improve the reliability and consistency of the findings, future work will focus on collecting data from a larger sample size and standardising the data collection method across cohorts.

1. Darbari et al. The European Journal of Haematology, 2020; 105, 237–246.

2. Adekunle et al. Blood Science, 2020; 2(4), 109-116.

3. Dormandy et al. The Journal of Public Health (Oxf), 2018; 40(3), 291–295.

4. Udeze et al. Advances in Therapy, 2023; 40, 3543–3558.

Topic: 003–Clinical and epidemiological studies

M.A. Adeturinmo¹, S.E.Q. Essilfie-Quaye¹, C.L. Lee¹, S.M. Mackie², S.I. Ismael¹, F.D. Daley³, B.C. Chivers², N.E.I. Igbineweka¹, P.R. Reddy⁴, W.M. Mitchell¹, J.M. Makani³, M.L. Layton², S.O. Okoli²

Imperial College London¹, Imperial College Healthcare NHS Trust², Muhimbili University of Health and Allied Sciences³, University of KwaZulu-Natal⁴

Background: Recruitment is an essential aspect of clinical research, as poor recruitment can undermine a study's scientific value or delay its progress.¹ Electronic health records (EHR) contain a wealth of clinical data and can be used to identify study participants and their characteristics. However, EHRs may not include all the essential information for clinical research eligibility screening.² The use of EHR to identify the ethnicities of participants in the non-sickle cell disease (non-SCD) cohort of a study on ‘the genomic integrity and safety of stem-cell gene therapy in SCD’³ was reviewed. We report on the recruitment experience, highlighting the importance of accurate and consistent ethnicity recording as a key demographic in clinical research. The study was conducted with the approval of the Imperial College Healthcare Tissue Bank, REC 3 Wales, and funded by the Bill and Melinda Gates Foundation.

Aim: To assess the use of EHR in determining patient ethnicity during the recruitment of ethnically matched non-SCD controls.

Methods: Research practitioners collected data from the EHR system (Cerner), of five general haematology clinics at Hammersmith Hospital⁴ over a 2-week period. These data consisted of generic patient demographic information, excluding ethnicity. Patient ethnicity was identified using a multistep search strategy and categorised as follows:

Basic search: Medical records number (MRN) was used to identify each patient's ethnicity on Cerner, which was recorded with other data.

Deeper search: If a patient's ethnicity was categorised as “other—not known” or “other—any other ethnic group,” structured patient notes were examined for qualitative information potentially identifying a patient's demographic. If ethnicity remained unidentified, additional search applications within Cerner were used to investigate a patient's NHS National Care Records Service (NCRS) or Clinical Document Library (CDL) to determine their ethnicity. Patients were described as ‘unknown’ where all avenues explored failed to identify ethnicity.

Results: During the screening process, 48 patients were evaluated to determine the ethnicities of potential participants for the non-SCD control cohort. The preliminary ‘basic search’ identified ethnicities for 52.08% of the patients, leaving 47.92% to be determined. A subsequent ‘deeper search’ uncovered an additional 31.25% of ethnicities, with 16.67% remaining ‘unknown’ at the end of the 2-week period.

Discussion: A comprehensive recruitment process is imperative to ensure that any clinical study accurately represents the community it aims to focus on. Whilst a “deeper search” identified an additional 31.25% of patient ethnicities, this required an extensive search through qualitative information. Such an approach may not be sustainable for large cohort studies and highlights the need for a more time-efficient and structured method for ascertaining ethnicity for the purpose of clinical research. Expanding the sub-categorisation of ethnicities could reduce the number of individuals recorded as “unknown.” Improving the rigour of EHR data with respect to ethnicity would facilitate more reliable access to an important patient demographic and enable future ethnicity-matched cohort studies to be conducted more efficiently.

Topic: 003–Clinical and epidemiological studies

G. Kazadi¹, D. Mbuyi², R. Kitenge³, S. Mpaka⁴, R. Ngiyulu⁵, J.L. Gini⁶, L. Tshilolo⁷

Departement de Pédiatrie, CH Monkole¹, Faculté des Sciences, Université de Kinshasa², Centre de Formation et d'Appui Sanitaire, CEFA-Monkole³, Institut National de Statistique⁴, Département de Pédiatrie, Université de Kinshasa⁵, Service d'hématologie Pédiatrique, Ciliniques Universitaires de Kinshasa⁶, Département de Pédiatrie, UOM and Institut de Recherche Biomédicale-CEFA⁷

Introduction: Sickle cell disease (SCD) is one of the most prevalent genetic disorders worldwide, with an estimated incidence of 230,000 cases per year in sub-Saharan Africa and a high prevalence (1%) in the Democratic Republic of Congo (DRC). Stroke is a major complication of SCD, associated with significant morbidity and mortality. Transcranial Doppler (TCD) ultrasonography is the recommended non-invasive method for stroke prevention in young SCD patients.

Objective: This study aims to determine the prevalence of pathological TCD findings in a cohort of young Congolese patients with SCD and to assess the association of these findings with haematological parameters.

Population and Methods: This cross-sectional study involved 150 Congolese children with SS homozygous SCD, aged 2–16 years (mean age: 8.5 ± 4.0 years), who were in a steady-state condition and followed from January 1 to December 31, 2013. TCD was performed using the STOP I method on major cerebral arteries. Stroke risk was categorized based on the time-averaged maximum mean velocity (TAMMV) in the middle cerebral artery (MCA): <170 cm/s (no risk), 170–199 cm/s (borderline/conditional risk), and ≥200 cm/s (pathological risk).

Results: The prevalence of pathological TCD was 4%, while conditional TCD prevalence was 10%. The mean blood velocity in the MCA was 114.0 cm/s. Significant differences were observed in white blood cell count (WBC) (p = 0.003), hemoglobin (Hb) (p < 0.001), hematocrit (Hct) (p < 0.001), and mean corpuscular volume (MCV) (p = 0.005) when comparing normal and at-risk TCD groups (conditional and abnormal). However, no significant association was found for the categorical corresponding parameters.

Conclusion: Overall, 14% of patients were at risk of stroke, highlighting the importance of integrating TCD into the routine monitoring of children with SCD. This practice could help prevent overt strokes through the implementation of chronic blood transfusion programs or the use of hydroxycarbamide.

Topic: 003–Clinical and epidemiological studies

M. Shehu¹, S. Yohanna², M. Ihekaike¹, G. Ebuga³, J. Musa⁴, G. Felix⁵, E. Attah⁶, A.O.D. Ofakunrin⁷, W. Atoyebi⁸, B. Ojo⁹, B.P.D. Inusa¹⁰

Department of Paediatrics, College of Medicine and Health Sciences, Bingham University/Teaching Hospital¹, Department of Family Medicine, College of Medicine and Health Sciences, Bingham University/Teaching Hospital², Department of Pharmacy, Bingham University Teaching Hospital³, Department of Nursing services, Bingham University Teaching Hospital⁴, Department of Haematology, Bingham University Teaching Hospital⁵, Department of Administration, College of Medicine and Health Sciences, Bingham University/Teaching Hospital⁶, Department of Paedatrics, University of Jos/Jos University Teaching Hospital⁷, Department of Clinical Haematology, Churchill Hospital⁸, Sickle Cell Cohort Research (SCORE) Foundation⁹, Kings College London, London, United Kingdom¹⁰

Background: Hydroxyurea is a disease-modifying therapy for sickle cell disease (SCD) that has been shown to reduce morbidity and mortality, as well as enhance the quality of life for patients. Despite its benefits, the uptake of hydroxyurea remains low in low- and middle-income countries (LMICs) due to cost, insufficient knowledge, and lack of expertise in its administration. Implementing hydroxyurea in a resource-limited setting involves navigating various enablers and barriers to maximize the therapy's potential benefits for patients with SCD.

To address these challenges, the Sickle Cell Cohort Research (SCORE) Foundation, a registered charity, collaborated with Bingham University Teaching Hospital (BhUTH), a faith-based hospital in Jos, Nigeria, in 2022. This collaboration was designed to train healthcare workers (HCWs), including physicians, pharmacists, nurses, and laboratory scientists, on comprehensive care for SCD, including the use of hydroxyurea. The Foundation, through the generous support of the Nigerian Christian Fellowship in the United Kingdom, provided free hydroxyurea for treating patients with SCD.

Aims: This study aimed to describe the implementation of hydroxyurea treatment and its impact on patients with SCD at BhUTH.

Methods: This cross-sectional study utilized data from the hemoglobinopathy clinic at BhUTH, spanning August 2022 to December 2023. HCWs attending to patients with SCD were trained on the role and therapeutic benefits of hydroxyurea in SCD, with hydroxyurea provided free of charge to the patients. Patients and/or caregivers were educated about the medication, and all patients older than 9 months were offered hydroxyurea according to current recommendations. The patients received a fixed dose of 20 mg/kg and were initially monitored after four weeks and subsequently every three months. Prior to this period, only two patients were on hydroxyurea, which had been commenced at another facility. Data extraction was performed by the data manager and validated by the lead researcher through comparison with the clinic data. Extracted information included demographic characteristics, hydroxyurea history, and basic laboratory parameters. Data analysis was conducted using SPSS version 23.0 for Windows, with data summarized and presented using descriptive statistics.

Results: The study included 149 patients with SCD aged 1 to 34 years; 53% were female, and about 65% were from a low socioeconomic class. Hydroxyurea uptake increased from 5% (4/20 patients) prior to the program implementation in August 2022 to 100% (149/149 patients) as of December 2023. Sickle cell healthcare service utilization through clinic attendance increased by 370% (from 40 to 149 patients). The majority (98.7%) of the 149 patients had received hydroxyurea for 6 months or longer. Their mean haemoglobin values increased from 8.3 to 8.9 g/dLl (after 3 months of hydroxyurea), while their mean total white blood cell count decreased from 9300 to 5200/mm³. Furthermore, creatinine levels increased from a baseline median value of 34 (23–50) to 44 (37–51) after 12 months of hydroxyurea. Alanine transaminase levels decreased from a median of 23 (14–27) at baseline to 19 (15.3–29.5) after 12 months, and alkaline phosphatase levels decreased from 140 (99–220) to 109 (75–143), while aspartate transaminase levels remained unchanged. Most patients reported significant improvement in their health status.

The barriers to implementation included difficulty enlisting local donors, accessing health insurance schemes, and ensuring the long-term sustainability of the program.

Conclusion: Hydroxyurea improves the health status of SCD patients. Its uptake in low- and middle-income setting is enhanced by training healthcare professionals and subsidising the cost of hydroxyurea treatment.

1. Yawn et al. Journal of the American Medical Association, 2014; 312, 1033–1048.

2. McGann et al. The Lancet Haematology, 2016; 3, e491–e500.

3. Tshilolo et al. The New England Journal of Medicine, 362(10), 2046–2056.

4. Ofakunrin et al. African Health Sciences, 2021; 21(2), 765–774.

This study has been conducted within the African Research and Innovative initiative for Sickle cell Education (ARISE) that has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 824021.

Topic: 003–Clinical and epidemiological studies

A.C. Adriana Costa¹, J.L. Joana Lage¹, I.M. Inês Mendes¹, M.M. Marta Moniz¹, C.A. Catarina Amorim¹, H.A. Helena Almeida¹, P.N. Pedro Nunes¹, A.V. Ana Ventura¹, T.F. Teresa Ferreira¹, C.E.M. Carlos Escobar¹

Hospital Prof. Doutor Fernando Fonseca¹

Background: Periodic blood exchange transfusion (ET) is a treatment modality commonly used to manage pediatric sickle cell disease (SCD), especially when complicated by cerebrovascular disease. The main goal of ET therapy is to prevent vasoocclusion and to improve tissue perfusion by removing sickled red blood cells. Given the central role that inflammation plays in SCD pathophysiology, different studies reported high levels of pro-inflammatory cytokines in these patients. We hypothesised that ET might also reduce pro-inflammatory mediators.

Aims: Evaluate the impact of ET on inflammatory markers in patients with SCD included in a chronic ET program.

Methods: Prospective and observational study of pediatric patients with SCD (HbSS genotype) enrolled in a chronic automated ET program at a level II Portuguese hospital. Patients with acute exacerbations of the disease were excluded. All informed consents were obtained. Blood tests were collected up to 24 h before and after ET for evaluation of haematological parameters and proinflammatory cytokines - interleukin (IL) 6, IL-8, IL-1, C-reactive protein (CRP), procalcitonin (PCT) and tumour necrosis factor α (TNF-α). Statistical analysis was performed in SPSSv25®. Student's t-test was applied to compare the two different times; significance level p < 0.05.

Results: We analysed data between October 2022 and May 2024, including 31 children (48% male; mean 11 years old). Among these patients, 14 did not have ETs before entering the study and 17 were already on the chronic ET program with a mean of 13 procedures performed. Cerebrovascular disease prevention (primary and secondary) was the most common indication for enrollment in the program (81%). Only 2 patients were not medicated with hydroxyurea, due to its adverse effects.

A total of 286 ETs were analysed. The number of procedures per patient varied 3–16 (mean = 9), separated by 38 days on average. There were no major adverse events related to the technique. None of the patients had hospitalisation during the study period due to disease complications. The average haemoglobin (Hb) level increased around 1.5 g/dL from pre-ET to post-ET. HbS reduction was 69% (37.6% ± 12.2% to 11.8% ± 7.4%; p < 0.001); leukocytes also reduced significantly, around 20% (p < 0.001). Before ET, IL-1 was altered in 49% of patients, procalcitonin in 50%, and ferritin in 61% (concerning the reference laboratory value). In contrast, IL-8, IL-6, CRP, and TNF-α were within normal range pre-ET in most patients (99%, 84%, 83% and 84% respectively). Differences between pre and post-ET in CRP, IL-6, IL-8, PCT, ferritin, and TNF-α serum concentration were not significant. The serum level of IL-1 was significantly higher pre-ET, declining from 51.6 ± 80.5 to 40.6 ± 70.3 pg/mL (p < 0.001). Moreover, there was a significant mean difference in pre-ET IL-1 values between patients who started the ET program for the first time (65.2 ± 87.4 pg/mL) when compared to the group who already underwent ET before the beginning of the study (41.0 ± 73.4 pg/mL, p = 0.03), with a difference of 22.6 pg/mL, 95% CI [2.1–43.2].

Summary/Conclusion: In conclusion, ET is safe and effective in reducing HbS and leukocytes, but may also induce a decrease in IL-1, which represents a biomarker of inflammation in SCD.

No acute exacerbations were observed in the cohort undergoing ET, corroborating its prevention role. However, more studies are needed to clarify the pathophysiology of cytokines in SCD and its complications.

Topic: 004–Infection, autoimmunity, nutritional deficiencies

B.M.G. Al Fugair¹

Dubai Health - Thalassemia Center¹

Background: Sickle cell disease (SCD) is considered a multi-organ disorder and has an acute and chronic complications including gastrointestinal system. Abdominal pain in SCD could be contributed to vaso-occlusive crises, ischemic colitis, cholelithiasis, hepatitis, splenic, or hepatic sequestration. Co-existence of SCD and inflammatory bowel disease (IBD) is not common in children and presentation of abdominal pain, jaundice, poor weight gain, fatigue, hyperbilirubinemia, and elevated liver enzymes are mainly attributed to SCD complications and might delay the diagnosis and treatment of IBD.

Aim: To highlight the rare coexistence of SCD and IBD and the challenges in the diagnosis and management of both diseases to ensure better outcome.

Case description: This is a case series of 3 pediatric patients with sickle cell disease on hydroxyurea therapy following in Dubai Thalassemia Center. All of them has positive direct coombs test and low baseline hemoglobin. All of them had often episodes of abdominal pain which was managed at home or in emergency short stay and attributed to sickle crises. First patient (13 years old girl) was investigated for frequent episodes of acute severe anemia, abdominal pain, mouth ulcers, weight loss, bloody painful hemorrhoids and high calprotectin. Endoscopy findings confirmed crohns disease and started on immunsuppressive therapy and therefore hydroxyurea was stopped. Second patient was referred to gastroenterologist at age of 8 years in view of persistent elevated liver enzymes for more than one year with failure to thrive and was diagnosed with autoimmune liver disease in view of positive autoimmune serology including antinuclear antibodies (ANA), anti-smooth muscle antibody (ASMA) with high immunoglobulin G and positive liver biopsy findings. She was started on Azathioprine and 1 year later she developed rectal bleeding and colonoscopy support the diagnosis of ulcerative colitis which was managed with sulfasalazine and corticosteroids. Hydroxyurea was stopped and started on regular simple blood transfusion program. Third patient was referred in view of recurrent bloody diarrhea, failure to thrive and chronic fatigue, colonoscopy findings confirmed ulcerative pancolitis (UC), with an element of backwash ileitis. He was started on Mesalazine. Hydroxyurea was stopped and started on regular blood transfusion program.

Conclusion: It's important to highlight the concurrent cases of both SCD and autoimmune diseases like IBD. This rare co-existence of both diseases might provide a management dilemma especially the hydroxyurea use while patient on immunosuppressive therapy and use of corticosteroid in the management of IBD which might trigger vaso-occlusive events in SCD. I believe this the first case series in UAE.

Topic: 004–Infection, autoimmunity, nutritional deficiencies

M. Sumbul¹, M. Nadeem¹, M. Ali¹, A. Iqbal², A.H. Kandhro²

National Institute of Cardiovascular Diseases¹, Sindlab Diagnostics²

Background: Pakistan is a malaria endemic country which remains prevalent throughout the year especially in Karachi region due to moderate climate. Incidental malarial parasites detection and reporting during hemoglobinopathies screening by HPLC or any other reason for peripheral smear examination is a noteworthy occurrence in the realm of diagnostic medicine. This unintended discovery holds significant clinical importance since malaria at times leads to severe anaemia and patients are wrongly screened for hemoglobinopathies and if not reported may result in unnecessary financial burden as well as increased morbidity and mortality. It is therefore imperative to perform peripheral smear examination with added intent to detect malarial parasite in all samples received for hemoglobinopathies.

Aims: To determine the frequency and clinical implications of incidental malarial parasite detection on peripheral blood smears screened for hemoglobinopathies.

Methods: This cross-sectional retrospective study included 124 patients samples screened for Hemoglobin disorders from Nov'22 to Jan'23, after heavy monsoons. Ethical approvals were taken. CBCs were performed by automated analyzers, smears were stained with Leishman stain and reviewed for morphological features and malarial parasites. Screening for hemoglobinopathies was performed by HPLC (Biorad Variant) with positive controls. Abnormal Hb peaks were noted and Hb A2 ≥3.9% was set as the cut off limit for Beta thalassemia minor.

Results: Out of total 124, 45 were males and 79 females with a mean age of 17.5 years ±15. Mean Hb was 8.0 ± 2.7 g/dL. Incidental malaria parasites detection were noted in 18 (14.5%), including 12 (9.7%) showing Plasmodium vivax, 03 (2.4%) Plasmodium falciparum and 03 (2.4%) mixed infestation. Coexistent malaria/hemoglobinopathy seen in 04(3.2%) cases, 03(2.4%) with Thalassemia minor & P. vivax and 01(0.8%) with Hb D Trait & P. falciparum. As anticipated, 15 out of 18 malarial cases were from underprivileged areas of Hub, Karachi.

Conclusion: The incidental findings of malarial parasites underscore the continued significance of peripheral blood smears esp. in malaria-endemic areas. Finding incidental falciparum can be crucial as this parasite is responsible for severe, life-threatening malaria. Individuals with hemoglobinopathies may have some protection against severe malaria because of the altered Hb interference with the growth of parasite in red blood cells. This protection is not absolute, and people with hemoglobinopathies can still contract malaria.

Topic: 005–Ageing and end organ damage

H.K.G. Goren¹, T.T. Tan², M.O.G. Ozari Gulnar³, M.A. Akyildiz³

Koc University Hospital, Department of Internal Medicine¹, Koc University Hospital, Department of Hematology², Koc University Hospital, Department of Gastroenterology³

Introduction: Sickle cell hepatopathy (SCH) is a spectrum of liver diseases associated with sickle cell disease (SCD), encompassing acute hepatic crisis, acute intrahepatic cholestasis, acute hepatic sequestration, and chronic cholestasis, along with complications of multiple transfusions, including viral hepatitis and iron overload.^1,2 This report presents a case of SCH presenting with cholestasis.

Case Presentation: A 19-year-old male patient with a diagnosis of SCD, followed by the Hematology department, presented to the hepatology clinic with a one-and-a-half-year history of jaundice, which had worsened recently. Hyperbilirubinemia had been present since 2016 but became more pronounced after the initiation of an exchange transfusion program in early 2022, with eight exchange transfusions performed. The frequency of painful crises had increased in the past year.

On presentation, the patient's laboratory values were as follows: albumin 41.2 g/L, ALT 74 U/L, AST 128 U/L, GGT 78 U/L, ALP 248 U/L, total bilirubin 16.7 mg/dL, direct bilirubin 13.3 mg/dL, prothrombin time 11 s, INR 0.98, WBC 13.09 K/uL, HGB 8.4 g/dL, Hct 22, Plt 568 K/uL.

Physical examination revealed icteric sclera and skin, a palpable liver 2 cm below the costal margin, an open Traube's space, and mild tenderness on deep palpation of the right upper quadrant. Fibroscan revealed a CAP of 166 dB/m and a liver stiffness measurement (LSM) of 16 kPa. Upper GI endoscopy did not reveal any varices.

Liver biopsy showed sickle cell hepatopathy, sinusoidal dilatation, sequestration of sickled erythrocytes in the sinusoidal space, hepatocanalicular cholestasis, mild damage to bile ducts, biliary metaplasia in hepatocytes, and multifocal early sinusoidal fibrosis. These findings were consistent with hepatobiliary involvement of sickle cell anemia.

The patient was referred to the Hematology clinic for further management and discharged.

Discussion and Conclusion: SCD is a rare disease, and SCH is even rarer. Elevated liver function tests are often overlooked in these patients during outpatient follow-up. Increased awareness in Hematology clinics is necessary for the detailed evaluation of these cases and referral to Hepatology specialists. It should be noted that appropriate treatment of complications can significantly improve the patient's clinical status and quality of life.

Topic: 005–Ageing and end organ damage

S.T. Twumasi¹, L.A.B. Antwi Boateng², E.O.A. Odame Anto¹

Kwame Nkrumah University of Science and Technology¹, Kwame Nkrumah University of Science and Technoloy²

Background & Aim: Renal injury is a common consequence of sickle cell disease (SCD). Conventional renal function tests such as serum creatinine, urea, and eGFR show abnormal results in SCD only when there is extensive renal damage. The aim of this study was to determine the predictive role of creatinine and urea as biomarkers of nephropathy in SCD.

Methods: This present study recruited 104 SCD participants and 80 healthy subjects. All participants were 18 years and above and in a steady state. Participants' information was thoroughly documented using a structured questionnaire and patient case records. Venous blood and urine were collected for laboratory analysis.

Results: Using the Receiver Operator Characteristics analytical tool, UACR with area under the curve (AUC) = 1.00, p < 0.0001, cut-off = 29.71 mg/g, sensitivity = 100% and Neutrophil Gelatinase Associated Lipocalin (AUC = 0.74, p < 0.0001, cut-off = 5.72 ug/L, sensitivity = 91.2%) had relative high significant performance when compared with creatinine and urea with AUC = 0.618, p = 0.087, sensitivity = 47.1% and AUC = 0.531, p = 0.693, sensitivity = 41.2%, respectively.

Summary and Conclusion: Creatinine and urea were found to have low sensitivities when compared to UACR and NGAL. Creatinine and urea are therefore not good predictors of nephropathy in steady state SCD patients. NGAL and urine albumin-to-creatinine ratio better predict nephropathy in SCD.

Topic: 006–Health services and outcomes research including psychology

V. Paintsil¹, E.X. Amuzu², Y.G. Oppong-Mensah², E. Ahmed³, L. Osei⁴, B. Eklu², S.Y. Abubakar², L. Osei-Tutu², D. Ansong¹, A. Osei-Akoto¹, F.S. Sarfo⁵

Department of Child Health, School of Medical Sciences, Kwame Nkrumah University of Science and Technology¹, Sickle Cell Unit, Komfo Anokye Teaching Hospital², Directorate of Laboratory Medicine, Komfo Anokye Teaching Hospital³, Directorate of Transfusion Medicine, Komfo Anokye Teaching Hospital⁴, Department of Internal Medicine, School of Medical Sciences, Kwame Nkrumah University of Science and Technology⁵

Background/Aim: Sickle cell disease (SCD) is the commonest clinically significant hemoglobinopathy.¹ Increased awareness about the disease and implementation of evidence-based treatment guidelines can lead to better health outcomes for the patient. However, there is a gap in management as healthcare providers (HCPs) still lack the confidence and adequate experience needed to manage patients appropriately leading to poor health outcomes for patients.² The study aimed to evaluate the level of knowledge about SCD and its management among HCPs in 4 regions of Ghana and the impact of a structured training program on their knowledge.

Methods: This prospective study utilized the SPARCo Standards of Care for Sickle Cell Disease in sub-Saharan Africa clinical recommendations for SCD management as training material for the HCPs. A curriculum and standard slides were developed by SCD experts from the recommendations. A one-day workshop highlighting the general overview of SCD, diagnosis, health maintenance, and acute and chronic complications was then organized. HCPs were drawn from 45 facilities and had a pre-training test and a post-training test immediately after the workshop. Data was entered into REDCap and analyzed using Stata 17.0.

Results: A total of 436 HCPs were trained from 51 healthcare facilities. Approximately 80% of the facilities involved in the training were secondary level facilities with 3% being primary healthcare facilities. The training was mostly attended by females (61%) and nurses of various levels (50%). The average age of the participants was 33 years (20–64 years) with an average overall working experience of 7 years (<1–30 years). Average number of years working with SCD patients was approximately 5 years (<1–20 years). Most (93%) HCPs had experience with SCD patients but only 42.7% reported using a form of guideline for the care of SCD patients.

The average score in the pre-training test was 8.4/20 (SD:3.3) increasing to 13.1/20 (SD:3.6) in the post-training test. The average proportion of persons indicating a correct answer for a question was 50% at pre-test increasing to 68.8% in the post-test. The greatest improvement in correct response from pre-test was on the question of clinical presentation of SCD (41.9%) followed by a question of substitute for persons allergic to Penicillin V (41.4%).

Conclusion: This study showed that a minority of HCPs managing SCD patients use any standardized guidelines and training on the use of these guidelines led to an improvement in their knowledge.

Topic: 006–Health services and outcomes research including psychology

M.r.s. Srivastava¹

Ministry of Health & Family Wefare¹

Sickle cell is highly prevalent in tribal areas in India. considering the importance Sickle Cell Anemia Elimination Mission has been launched at the national level by Honourable Prime Minister of India on July 1, 2023 at Shahdol (a tribal area, where the disease is highly prevalent) Madhya Pradesh.

Budget Announcement by Government of India:

The Budget 2023 contained an announcement which reads as “A Mission to eliminate Sickle Cell Anaemia by 2047 will be launched. It entails awareness creation, universal screening of 7 crore people in the age group of 0–40 years in affected tribal areas, and counselling through collaborative efforts of central ministries and state governments.” The lead Ministry in this regard is the Ministry of Health and Family Welfare (MoHFW) with the supporting Ministry being the Ministry of Tribal Affairs (MoTA). There are other stakeholders identified by the MoHFW in this Mission, including the State Governments

Training of Medical Officers & Paramedics: The launch Training programmes of State level Master trainers was initiated 28 August 2023 and was chaired by the Hon'ble Minister Tribal Affairs Sri Arjun Munda

Regional Training workshop are being conducted in states for sensitization of doctors, GPs, paramedics and communities

Screening: Sickle cell screening/health screening in EMRS schools in co-ordination with Ministry of Ayush on 21 February 2024 was Launched and now percolating to the peripheries. New born screening initiated in Government hospitals, Antenatal and Prenatal screening initiated in Government hospital.

Research: Under sickle Cell mission India also initiated the pre-clinical validation of indigenously developed CRISPR CAS 9 (gene editing for SCD) based cell therapy pipeline in progress, GMP lab for production completed.

Treatment: The small packages for treatment of Sickle cell disease have also been created which includes prenatal diagnosis, hydroxyurea treatment, safe blood transfusion in day care and hospital admission in crisis.

Sickle cell has also been included as a permanent disability in government of India Disability Act.

Establishment of Centres of Competence in each state which has all the necessary facilities for prevention & management of the SCD.

Newer rehabilitation therapies introduced through Ministry of Ayush to reduce down the pain crisis.

Conclusion: India will be able to reduce the disease burden by 2047, and ensures that no new born is affected with disease by 2047 onwards.

1. Government of India guidelines - Sickle cell Mission.

Topic: 006–Health services and outcomes research including psychology

L. Thaniel¹, B. Speller-Brown¹, S. Hardy¹, D. Darbari¹, R. Hyppolite¹, H. Olowolayemo¹, A. Campbell¹

Children's National Hospital¹

Background: The COVID-19 pandemic posed unique challenges for many families in the United States and around the world. Although a number of studies have examined the pandemic's impact on families' financial stability, there is limited research on its impact on social determinants of health (SDoH) in families affected by sickle cell disease (SCD).

Aims: The study aims were to examine SDoH data collected at multiple points during the COVID-19 pandemic among families affected by SCD. The study period was divided into two key phases: early pandemic (2020 to mid-2022) and late pandemic (late-2022 to 2024). We sought to assess differences between early and late pandemic in terms of food security, housing, and employment status among families with a child with SCD.

Methods: Caregivers of children from birth to 21 years of age with SCD were recruited for the study during clinic visits and hospitalizations. They were asked to complete a survey about food security, housing, and employment status over the past 12-months. Informed consent was obtained from all participants.

Results: Fifty-nine unique caregivers completed the survey during the early pandemic phase; 60 unique caregivers completed the survey during the late pandemic phase. Eighty-four percent (N = 100) of caregivers were female; 96% (N = 113) were Black or African American. Fifty-seven percent (N = 67) of caregivers were born in the U.S., while 43% (N = 51) of caregivers were born outside the United States. Twenty-seven percent (N = 24) earned $4000 or more per month, while 42% (N = 47) earned less than $2000 per month. Forty-seven percent (N = 54) of caregivers were married and 69% (N = 82) of caregivers had some college education or higher. During the early pandemic phase, 40% (N = 23) of caregivers reported concerns about their food running out, which decreased to 24% (N = 14) in the late pandemic phase. Equal proportions of caregivers (36%; N = 21) worried that their food would not last and that they would not have enough money to buy more during the early and late pandemic phases. Thirty-two percent (N = 19) of caregivers could not afford balanced meals during the early pandemic phase, which decreased to 28% (N = 17) in the late pandemic phase. Thirty-two percent (N = 19) of caregivers relied on low-cost foods during the early pandemic phase, while 30% (N = 18) did so in the late pandemic phase. Fifteen percent (N = 9) of caregivers reported cutting the size of meals during the early pandemic phase, which increased to 25% (N = 15) during the late pandemic phase. Forty percent (N = 23) of caregivers reported experiencing difficulties paying their rent or mortgage during the early pandemic phase, which decreased to 32% (N = 19) in the late pandemic phase. Eighteen percent (N = 9) of caregivers reported either being laid off or furloughed from work during the early pandemic phase, which decreased slightly to 17% (N = 9) in the late pandemic phase.

Summary: In the United States, SDoH affects overall health outcomes more than medical care. In our study, a large proportion of families with SCD reported food, housing and employment issues during the pandemic, despite the implementation of financial measures by the federal government. Further research is needed to understand the long-term effects of the pandemic on SDoH in these families.

1. Khan et al. Pediatric Blood & Cancer, 2022; 70, 2.

Topic: 006–Health services and outcomes research including psychology

H.T. Mohammed¹, N. Ifere², C.Y. Tanimu³, J.O. Gani¹, H. Usman¹, L. Gwani⁴, B.P. Inusa⁵

Kaduna State University¹, Panaf International School², Kaduna State College of Education³, Kaduna State House of Assembly⁴, Kings College London⁵

Sickle cell disease is an unpleasant health condition being identified among students in higher education institutions. A critical component of the disease is the awareness of the disease among students in higher education. The global scantiness of SCD research calls for the need for this investigation in low- and middle-income settings. Building on the ecological mode by Urie Bronfenbrenner', the study investigates the awareness of the disease, the relationship among the students, and the availability of guiding documents/policies concerning the disease.

Background: Sickle cell disease, a hereditary condition that affects over 50 million people worldwide, is becoming more common (Acharya et al., 2023; John et al., 2020; Kato et al., 2018; Okocha et al., 2022). It is predicted that 15 million children will be born with sickle cell disease (Beri et al., 2021; Carden & Little, 2019) over the next 20 years, with sub-Saharan Africa carrying the majority of the disease's burden (Arnold et al., 2016; Inusa et al., 2018). Sickle cell disease is the most prevalent hereditary blood condition in Africa, with 75% of all cases occurring (Inusa et al., 2018; Wastnedge et al., 2020). This figure is predicted to rise as a result of globalization and population growth (Gouda et al., 2019).

In spite of this, sickle cell disease is frequently regarded as an unnoticeable disability (Berghs et al., 2021; Srikanthan, 2023) and is not well understood by the general public in some contexts. The poor understanding of sickle cell disease has led to disparities in care (Dyson et al., 2021), poor health outcomes (Hegeman et al., 2023), social marginalization (Depetris-Chauvin & Weil, 2018), discrimination (Ndula, 2023), stress (Dong et al., 2023), and stigmatization (Blakey et al., 2022; Buser et al., 2021). Other challenges are lack of government support for people living with the disease (Tusuubira et al., 2018). This study in Kaduna, Nigeria aims to investigate these issues using the ecological model of healthcare.

Aim: To determine the awareness of SCD by university undergraduate in the light of the ecological model framework.

Methods: A qualitative case study was carried out between May 2023 and June 2023 with 60 students of faculty of Arts in Kaduna State University, Kaduna Nigeria. Students from six departments which are English and Drama, Nigerian Language and Linguistics, French, Arabic, Christian Religion Studies, Islamic studies, and History. The semi-structured interviews were recorded, and the data were analyzed and interpreted by a thematic analysis.

Result: The discussion of findings was arranged in line with the four theoretical constructs.

The construct of Intrapersonal/individual factors (CIIF)

Findings from this study revealed that the respondents who are undergraduate students at KASU are aware of the existence of SCD, they know that the disease is hereditary but they are not aware of any support that students living with the disease receive from the university.

The construct of Interpersonal factors (CIF)

The major aspect identified as the interpersonal factor is that KASU students living with sickle cell disease are bold, shy, arrogant, and need attention always. More so, students living with SCD socialize and interact very well with other students while others keep to themselves.

Construct of Community Factors (CCF)

Additionally, the construct of community factor uncovered three key aspects which are people try to avoid them in the community which is compared to stigmatization. Secondly, they are called names such as sicklers meaning that they will die at any moment, and thirdly are denied certain rights and privileges such as job opportunities.

The construct of Society Policy Factors (CSPF)

This study also identifies the availability of rules/laws/policies to serve as guidelines on SCD in society. The findings revealed that the undergraduate students are not aware of the existence of any policy in KASU or anywhere. The finding also exposed that the availability of the policies/guidelines/laws will create awareness about the disease give statistics about the disease and help in the prevention and management of the disease

Summary: The respondents are aware of the existence of SCD and that it is hereditary. People living with sickle cell conditions are stigmatized and assumed to have a short lifespan. Despite the level of awareness of the disease in KASU, there are no guiding principles to guide and protect students living with SCD.

Conclusion: The Urie Bronfenbrenner's (Bronfenbrenner, 2021; Xia et al., 2020) model developed in the 1970s applied in this study has aimed to create awareness and increase knowledge in society about SCD. This, in the long run, is expected to lead to positive changes in SCD healthcare outcomes, increase the quality of life of those living with SCD, to reduce the burden of the disease, and also attract intervention in Low-and-income country Settings.

1. B Acharya et al. Recent progress in the treatment of sickle cell disease: an up-to-date review. Beni-Suef University Journal of Basic and Applied Sciences, 2023; 12(1), 38.

2. AS Adewoyin. Management of Sickle Cell Disease: A Review for Physician Education in Nigeria (Sub-Saharan Africa). Anemia, 2015, e791498. doi:10.1155/2015/791498

3. Akinsete. Treatment of Sickle Cell Disease in Sub-Saharan Africa: we have come a long way, but still have far to go. Journal of Global Medicine, 2022. https://globalmedicine.co.uk/index.php/jogm/article/view/79

4. H Bello-Manga et al. Epidemiology and treatment of relative anemia in children with sickle cell disease in sub-Saharan Africa. Expert Review of Hematology, 2016; 9(11), 1031–1042. doi:10.1080/17474086.2016.1240612

5. GO Boateng et al. Best practices for developing and validating scales for health, social, and behavioral research: a primer. Frontiers in Public Health, 2018; 6, 366616. doi:10.3389/fpubh.2018.00149

6. U Bronfenbrenner. Ökologische Sozialisationsforschung. Ein Bezugsrahmen. In Handbuch Bildungs-und Erziehungssoziologie (pp. 1–11). Springer; 2021.

7. BP Inusa et al. Utilising the ‘getting to Outcomes®' framework in community engagement for development and implementation of sickle cell disease newborn screening in Kaduna State, Nigeria. International Journal of Neonatal Screening, 2018; 4(4), 33.

8. CC John et al. Hydroxyurea dose escalation for sickle cell anemia in Sub-Saharan Africa. New England Journal of Medicine, 2020; 382(26), 2524–2533. doi:10.1056/NEJMoa2000146

9. L McLaren, P Hawe. Ecological perspectives in health research. Journal of Epidemiology & Community Health, 2005; 59(1), 6–14. doi:10.1136/jech.2003.018044

Topic: 006–Health services and outcomes research including psychology

C. Jaja¹, J. Edem-Hotah², S. Ibemere³, R. Gibson⁴

University of South Florida¹, College of Medicine and Allied Health Sciences-Faculty of Nursing², Duke University³, Augusta University-Medical College of Georgia⁴

Background: Sickle cell disease (SCD) is a major contributor to child morbidity and mortality. The absence of early diagnosis through a laboratory-based newborn screening (NBS) program is a major barrier to the implementation of timely preventive measures in sub-Saharan Africa. Emergent, novel, inexpensive, point-of-care tests (POCTs), with analytic characteristics and field-tested performance comparable to laboratory methods, offer intriguing options for early diagnosis of SCD in primary health centers (PHCs) in limited resource settings.

Aims: This study explored key community stakeholders' acceptability of a nurse-led early diagnosis and clinical management of children under 5 years with SCD in one urban and one rural PHC in Sierra Leone, a SCD endemic country.

Methods: In this feasibility study of the Nurse Champion Model, the research aims include developing and assisting PHCs in implementing the model; evaluating processes/determinants of model implementation; and evaluating the model's effectiveness, acceptability, and effects on provider and client outcomes. We conducted seven focus group meetings with adults with SCD (N = 33), 10 focus groups with nurses (N = 57) four interviews with hospital administrators, and one focus group with nurse managers (N = 7). Eighteen interviews were completed with women in the third trimester of their pregnancy. Qualitative data obtained from the audio recordings of the interviews and focus groups were transcribed verbatim and data coded using Atlas ti version 8.4.4. qualitative software for thematic content analysis.

Results: The results presented in this report cover four major thematic areas as follows: management strategies, continuum of care, program success and sustainability, and community awareness of SCD screening. The interview data reinforced the necessity of continuum of care that includes preconception, genetic counseling, pregnancy, and early child care. Successful implementation is guaranteed when all stakeholders are informed and top clinical management support is assured. The importance of sustainability of early diagnosis programs was noted by numerous participants as well as the cultural barriers, and feminization of care for SCD.

Conclusion: The participants were unanimously interested in the availability and expressed strong interest in participating in a nurse-led program of care for early diagnosis and clinical management of children with SCD. Hospitals were identified as the preferred location for such programs. The majority of pregnant women would prefer their husbands present when newborn screening results are shared. Knowledge of SCD and early treatment were the consistent rationale for having newborns tested. These findings will inform the design of protocols, including newborn recruitment plans, neonatal unit staffing, and oversight, care coordination, nurse training, and media promotion campaign implementation strategies to operationalize the Nurse Champion Model intervention. Our program's major goal is to evaluate the feasibility of a nurse champion model for the management of young children with SCD. This innovative task-shifting intervention would embed nurses in PHCs to provide NBS, patient education, and care coordination and management.

Topic: 006–Health services and outcomes research including psychology

H. Jerman¹, S. Ndoro¹, O. Taiwo², D. Seviar², S. Babiker¹

Evelina London¹, Guys and St Thomas NHS Trust²

Background: There is evidence that sickle cell disease (SCD) and thalassemia patients' transition to the adult service is linked with increased mortality (Kavanagh et al, 2022). It can be an extremely challenging time for young people (Fenchel et al., 2023), with high rates of non-attendance and non-compliance. There has been a longstanding multidisciplinary team (MDT) transition clinic at Guys and St Thomas NHS Trust, with the Evelina London. However, there has not been a transition clinical nurse specialist (CNS) between 2019 and 2024.

Aims: The aim of this study was to identify compliance and attendance of SCD and thalassemia patients to the MDT transition clinic, and once they are transitioned to adult services.

Methods: The researchers did a retrospective audit of the electronic patient records for SCD and thalassemia patients, transitioned to adult services between 2019 and 2023. During this time, there was no transition CNS. Clinic notes were reviewed, to identify attendance to transition clinic, adult clinic, psychology input, admissions and compliance to tranfusions or hydroxycarbamide. Genotypes were also recorded.

Results: 95 patients were included in the audit, age 16–20 years. 87% of patients attended the MDT transition clinic. However, only 65% of these patients attended their first adult clinic within 1 year of attending the MDT clinic. 6.5% of patients were lost to follow up. 28 patients are on transfusions, of which 17% are non-compliant or attend infrequently. 28 patients are on hydroxycarbamide, of which 40% of patients are non-compliant in their first year post transition.

Conclusions: Despite implementation of the MDT transition clinic, there is still evidence of non-attendance and non-compliance to adult services, once transitioned. Audit outcomes will be repeated in one year, as a transition CNS has been introduced during 2024. It will also be useful, to survey the reasons why patients are non-compliant when they transition, to help improve outcomes further.

1. PL Kavanagh et al. Sickle cell disease: a review. JAMA, 2022; 328(1), 57–68.

2. F Lynette et al. Improving transition of emerging adults with sickle cell disease to adult care through a multidisciplinary process: the development of a transition clinic to support transition success. Blood, 2023; 142(Supplement 1), 5055.

Topic: 006–Health services and outcomes research including psychology

M.E. Houwing¹, M. Bruinooge¹, C. van Vulpen², H. van Bommel², S.A.M. Teuben¹, F. Petrij³, C.L. Harteveld⁴, A.M.S. Joosten³, M.H. Cnossen¹

Department of Paediatric Haematology and Oncology, Erasmus MC Sophia Children's Hospital, University Medical Centre Rotterdam¹, Pharos: Dutch Centre of Expertise on Health Disparities², Department of Clinical Genetics, Erasmus MC, University Medical Centre Rotterdam³, Department of Clinical Genetics, Leiden University Medical Centre⁴

Introduction: Sickle cell disease is a monogenetic autosomal recessively inherited disorder characterised by chronic haemolytic anaemia, vaso-occlusive episodes, and progressive organ dysfunction. As the concept of carriership can be experienced as complex, awareness regarding carrier status and disease implications when affected is limited among high-risk populations, but essential to improve. Educational materials to adequately inform individuals of all levels of health literacy, especially adolescents, about sickle cell disease carriership are therefore an unmet need.

Aims: The primary aim was to create understandable educational material that clarifies sickle cell disease carriership and the risks of disease, addresses misconceptions, and conveys the availability of adequate screening for carriership. The secondary aim was to describe the process of developing storytelling material for disease-educational purposes for healthcare professionals and researchers.

Materials and Methods: We used the manual for the development of visual stories in healthcare for youth provided by Pharos.¹ Illustrations and text were tested in individuals from the target audience using standardized questions provided by Pharos, and were adjusted according to test findings. Subsequently, the visual story was translated to English with editing for accuracy and understandability by two independent native English speakers. The understandability and actionability of the storytelling material were assessed using the Patient Education Materials Assessment Tool (PEMAT).²

Results: The storytelling tool (Figure 1) features a high-risk couple's desire for another healthy child, juxtaposed with a friend's child suffering from sickle cell disease. The concepts of carriership, disease inheritance, and the possibility of testing for carriership are introduced. The tool emphasizes public awareness and the importance of consulting primary care doctors for carriership testing, especially by individuals that (or whose ancestors) originally come from regions where malaria is endemic, as these coincide with a high prevalence of sickle cell disease carriership and disease. During testing of the visual story, one illustration was found to be confusing. It was modified according to test subjects' feedback. The PEMAT-score of the finalized storytelling material was 96%, indicating high understandability and actionability.

Conclusion: We report how to develop comprehensible and accessible storytelling material using scientific methodology to inform individuals about sickle cell disease carriership, disease symptoms, and the availability of adequate screening to establish (non)-carriership.

Figure 1: Title page of storytelling tool on sickle cell disease carriership.

Topic: 006–Health services and outcomes research including psychology

C. Jaja¹, S. Ibemere², J. Edem-Hotah³, R. Gibson⁴

University of South Florida¹, Duke University², College of Medicine and Allied Health Sciences- Faculty of Nursing³, Augusta University-Medical College of Georgia⁴

Background: Sickle cell disease (SCD) is a major contributor to childhood morbidity and mortality in African countries like Sierra Leone (SL). Limited early diagnosis programs, the limited number of physicians with expertise in hematology, combined with a dearth of extant strategies to combat SCD have led to a paucity of care for children affected by the disease in SL, a problem further compounded by the lack of public understanding of SCD, which perpetuates social stigma and myths about disease causation and results in few people seeking appropriate treatment.

Aims: We showcase the EASEL Project, a pilot project designed to empower the nursing workforce in Sierra Leone to perform early diagnosis, genetic counseling, and clinical management of sickle cell disease in children.

Methods: The EASEL project is an academic and private partnership initiative designed to provide basic comprehensive care to children within community hospitals while building capacity within the healthcare system for ongoing improvements in SCD clinical outcomes. The EASEL project leverages the nurse champion model and implementation science to promote the uptake of evidence-based health practices for SCD care. Three aims inform the EASEL project; (1) Conduct a formative evaluation to assess barriers and facilitators to the primary health center provision of SCD case management with a Nurse Champion model; (2) Create an implementation plan for the Sickle Cell Disease Nurse Champion Intervention using Implementation Mapping; and (3) Implement the Nurse Champion model and evaluate its determinants and implementation costs.

Results: The EASEL project will support nurses with the technical capacity to manage and increase opportunities for children living with SCD to receive uninterrupted access to basic preventative wellness care to experience improved quality of life and reduce overall under-five child mortality.

Summary/Conclusion: There is a need to integrate affordable SCD evidence-based solutions into the existing healthcare system in Sierra Leone. Newborn screening is urgently needed. Quantifying the public health burden of SCD in Sierra Leone needs to be conducted, and there is an urgent need for public awareness campaigns to combat stigma and misunderstandings about SCD and to provide genetic counseling opportunities and initiatives that promote disease avoidance.

Topic: 006–Health services and outcomes research including psychology

M.F. Musilimat Faleye¹, H.L. Hadiza Lawal¹, N.A. Niyi Adebiyi¹, J.F. Jamilu Faruk¹, H.A. Hafsat Ahmad¹

Ahmadu Bello University Teaching Hospital¹

NB: This study has been conducted within the African Research and Innovative initiative for Sickle cell Education (ARISE) that has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 824021.

Background: Sickle cell disease (SCD) is a hereditary blood disorder characterized by the production of abnormally shaped red blood cells when exposed to hypoxia causing blockages in blood flow, leading to pain, organ damage, and an increased risk of infections. The high prevalence of SCD in Nigeria is compounded by limited healthcare infrastructure, insufficient public awareness, and socio-economic barriers that impede effective disease management. Understanding the knowledge of home-based caregivers regarding SCD is vital in highlighting the gaps in awareness and understanding that may affect the quality of care provided.

Aim: This study aims to explore the knowledge of home-based caregivers on SCD in Nigeria. The research seeks to gather in-depth insights into caregivers' experiences, perceptions, and educational needs.

Methods: A qualitative research method was employed using a case study design with in-depth interviews. The interviews were audio-recorded and transcribed in the participants' native language (Hausa), which was later translated into English. Thematic analyses were performed.

The study was conducted at the paediatric Haematology clinic at Tertiary Hospital in Northern Nigeria. Data were gathered from 10 purposively selected home-based caregivers. Five of the participants each have children with SCD aged 0–5 years and 6–10 years respectively.

Results: From the data analysis, six major themes emerged. The participants understand SCD to be a hereditary disease that causes the blood cells to break down faster than normal. Most of the participants are of the opinion that SCD is caused by genes, and that if both parents carry the sickle cell trait, their children can be affected. Even though home-based caregivers demonstrated some level of awareness about SCD, they lack in-depth knowledge of sickle cell disease.

Conclusion: Home-based caregivers have a basic understanding of sickle cell disease. They recognize its genetic nature, the abnormal sickle-shaped red blood cells, and some associated symptoms such as pain. This basic knowledge equips caregivers to manage the disease effectively and seek medical care. However, there is a need to enhance their understanding and improve the quality of care provided to individuals with SCD.

Topic: 006–Health services and outcomes research including psychology

C.L. Morris¹, C.L.M. Morris¹

NHS Blood and Transplant¹

Background: National Health Service Blood and Transplant (NHSBT) Therapeutic Apheresis Services (TAS) provides lifesaving and life enhancing treatments to adults and children with sickle cell disorder (SCD) across England. Patients are treated on either our elective planned programmes or as an emergency out of hours (OOH) procedure. By using the Terumo Spectra Optia, red cell exchanges or depletion exchanges are performed to reduce the number of circulating sickle cells.

In 2023, TAS nurses performed 2273 red cell procedures with 165 of these being OOH. This equates to 19% of the total workload being dedicated to treating patients with sickle cell disorder. This is a 37% increase in red cell activity since 2020, with a forecast for activity to increase even further as MedTech funding is allocated, this will allow even more outreach services.

Aims: To support this workload, it is paramount that the service has a knowledgeable and skilled workforce who can provide the highest standards of treatment and evidence-based care to patients of all ages across all settings. The National Health Service (NHS) long term workforce plan (NHS England 2023) identifies the increasing number of people living with multimorbidity's and complex needs, and states that there is a need to alter the shape of the workforce and acknowledges Advanced Clinical Practitioners (ACP) as key contributors. Within the four pillars of advanced clinical practice (Health Education England, 2017), an ACP has the skills required to ensure a patient centred, effective and efficient service, which includes engagement with the patients. An ACP can scrutinise the research and supporting literature, and new ways of working can be identified and implemented using evidence-based practice to ensure the best outcomes for patients.

Results: In response to this TAS have now implemented the ACP role nationally to support the increasing workload. Clinical service improvement projects are at the forefront, which include introducing care coordinators to work with the NHS trusts which would improve collaborative working and patient experience for sickle cell patients. It has also been recognised that as an outreach specialist service performing red cell exchanges the information, we hold about our patients is generic and we do not actively perform a holistic assessment. Due to the complex needs of these patients living with a rare condition it is important that we involve them in decisions about their care. This includes thinking about what makes each person unique, and doing everything we can to put their needs first (Nursing and Midwifery Council (NMC) 2020). To achieve this, health care professionals (HCP) must work collaboratively with the service user and complete an assessment of their needs and preferences for care and treatment, this includes health, personal care, emotional, social, cultural, religious, and spiritual needs (Health and Social Care Act 2008). SDC predominantly affects the black afro Caribbean population. Patients with SCD feel that their care is disjointed, and they face inequalities with the healthcare system due to race (Sickle Cell Society 2021). It is therefore unacceptable that an assessment of these needs is not completed and could be perceived as a racial inequality and an ethnic health disparity (Kapadia et al., 2022).

Conclusion: Finally, TAS are about to embark on a national red cell audit – this will be a retrospective study looking at practice across all the units measured against set standards. The outcome of the audit is to create national clinical pathways and standards of care for all our sickle cell patients. The audit will be led by an ACP.

As the first ACP within NHSBT I would very much like to showcase the work we are completing at the ASCAT conference to improve multiple elements of care for patients requiring automated red cell exchanges delivered by TAS Nurses.

Topic: 006–Health services and outcomes research including psychology

A.D. Didio¹, V.G. Giannuzzi¹, N.A. Archer², E.G. Gani³, E.P. Peprah⁴, P.K. Kountouris⁵, F.B. Bonifazi¹

Fondazione per la Ricerca Farmacologica Gianni Benzi Onlus¹, Pediatric Hematology and Oncology, Boston Children's Hospital², Kaduna State University³, Department of Global and Environmental Health, New York University School of Global Public Health⁴, Molecular Genetics Thalassaemia Department, The Cyprus Institute of Neurology & Genetics⁵

Background: The International Hemoglobinopathy Research Network (INHERENT) aims to study genetic modifiers through large, multi-ethnic genome-wide association studies involving both pediatric and adult patients affected by haemoglobinopathies. INHERENT brings together nine existing international or regional consortia in the field of haemoglobinopathies, and hundreds of experts from all over the world.

The implementation of genetics/genomics into the global healthcare sector has advanced the need for standardized policy regarding all aspects of biospecimens handling and the whole data processing process, including data collection, storage, sharing and dissemination of the results.

This work aims to describe the applicable ethics and regulatory framework needed to conduct a researcher-driven multi-national genetic study involving humans.

Methods: Using a co-creation approach among researchers and experts in regulatory, ethical, legal and societal issues, key topics related to human genetic research were identified. The applicable international standards were collected consulting official sources. An online survey was conducted to identify the local rules.

Results: Three key topics related to human genetic research were identified: processing of personal data, clinical research, and biospecimens management. 26 internationally-applicable documents were identified; among them, 38.5% cover issues related to genetic research. With regards to the local ethical and regulatory landscape ruling human genetic research, specific laws, guidelines/recommendations ruling the processing of personal data and privacy have been released in most of the 32 surveyed countries.

Conclusions: Despite the availability of several international guidelines, there is no unique reference document for genetic studies without investigational drugs, i.e. outside the scope of Good Clinical Practice. Our analysis underlined the heterogenicity of the local frameworks. This affects the scientific community, leading to challenges in conducting this kind of clinical study.

Additional efforts should be considered to further promote an international harmonization process of the ethical and legal requirements for genetic multi-national studies in research-driven settings.

This work was initiated within the ARISE initiative (funded from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 824021) and its result will also be used to support the activities of the recently funded HELIOS COST action aimed at building a network of excellence for integrating, harmonising and spreading the existing knowledge on haemoglobinopathies (CA22119 – Haemoglobinopathies in European Liaison of Medicine and Science).

1. Kountouris et al. American Journal of Hematology, 2021, 96.

2. Dankar et al. Human Genomics, 2018; 12, 19.

3. Vlahou et al. Hypertension, 2021; 77, 1029–1035.

Topic: 006–Health services and outcomes research including psychology

Y. Dabo¹, M. Mamman², N.K. Umar³, A.A. Shariason², A.R. Bako⁴, Y. Arigbede², M. Abubakar²

Institute for Development Research and Training, Ahmadu Bello University, Zaria-Nigeria¹, Ahmadu Bello University, Zaria-Nigeria², University of Maiduguri, Nigeria³, Federal University Gashua, Yobe-Nigeria⁴

Background: Sickle cell disease (SCD) is the commonest inherited disorder of hemoglobin which afflicts people of different socio-economic backgrounds. In Nigeria, sickle cell disease patients are faced with the challenge of healthcare accessibility, thereby increasing their social, economic, and psychological burden.

Aims: This study aims at investigating views of sickle cell disease patients on access to healthcare services and the social, economic and psychological burden of sickle cell disease.

Methods: A cross-sectional study was undertaken among 333 purposively selected sickle cell patients in two secondary and one tertiary hospital across Kaduna state. Data were collected using a self-administered questionnaire on clinic days, Kendall's W statistics and frequency and percentage analyses were undertaken using Statistical Package for Social Sciences software version 25.

Results: There were 333 patients who participated in the study, of which, age group 15–19 years were the most (84.0%) and female constituted more than half (60%) of the participants. The majority (86%) had formal education cutting across different levels from primary to tertiary. In terms of the social, economic and psychological burden of sickle cell diseases on patients, pity and stigmatization (6.68x̄) and limited social outings (5.71x̄) were the most pressing social burden. The major economic burden identified was the cost of medical bills (6.11x̄) which is always high for most households. Furthermore, feeling of guilt being a liability for the family (5.73x̄) was the major psychological burden affecting SCD patients. Access to healthcare services revealed more than two-third (85%) of patients do not have insurance coverage, a good proportion (47.8%) travel more than 10 km to a facility for treatment. More than half of the participants reported that transportation to treatment center is affordable (60.1%) while waiting time to be attended to by a doctor, is usually over an hour (75%). Medication is always available (19.5%) but somewhat hardly affordable (48.4%). Adequacy of doctors is found to be very poor as (89.8%) but healthcare practitioners are welcoming to patients (90.0%).

Summary/conclusion: The burden of sickle cell disease on patients still prevails despite several clinical breakthroughs. It is evident that social, economic, and psychological burden of sickle cell disease can do unmeasurable harm to patients if not given any attention. Generally, access to healthcare services for sickle cell patients is still revealing to be underscored. Thus, there is need for constant patient's engagement to improve access to healthcare for SCD patients and curb the burden of the disease through non-clinical approach.

1. Hezekiah et al. Frontiers in Genetics, 2023; 14, 1052444.

2. Adigwe et al. Molecular Genetics & Genomic Medicine, 2023; 00, e2142.

3. Adigwe et al. Hematology, 2022; 27, 488–493.

Topic: 006–Health services and outcomes research including psychology

Z.G. Guardiola-Abbots¹, K. Bains¹

Guy's and St Thomas NHS Foundation Trust¹

Background: Discrimination within healthcare settings is a pervasive issue, affecting individuals based on gender, race, age, illness type, religion, language, economic status, and social standing (Hosseinabadi-Farahani et al., 2021). Structural policies favouring dominant racial groups result in unequal distribution of societal benefits (Williams et al., 2019). Marginalised individuals face devaluation and differential treatment, impacting their healthcare access and outcomes (Hamed et al., 2022). Racism and discrimination contribute to compromised mental and physical health, exacerbating health disparities (Paradies et al., 2015; Togioka et al., 2023).

People from the global majority, encompassing Black, Asian, Brown, dual heritage, and Indigenous individuals, often experience recurring discrimination in healthcare, particularly in the treatment of long-term conditions such as, sickle cell disorder (SCD) (Campbell-Stephens, 2020). Discrimination reduces trust in healthcare providers, leading to lower adherence to medical recommendations and treatments, resulting in poorer health outcomes (Cuffee et al., 2013; Haywood et al., 2014).

Aims: Aim to analyse how discrimination impacts treatment adherence.

Role of trust as a mediator in the relationship between discrimination and adherence.

Methods: This scoping review followed PRISMA-ScR guidelines, conducting a systematic search across five databases: Embase, PsychInfo, CINAHL, Medline, and Ovid. Search terms focused on “discrimination,” “trust,” and “adherence,” with inclusion criteria limiting studies to peer-reviewed empirical research in English up to April 2024. Only observational studies exploring trust mediation between discrimination and adherence among the global majority population were included. Critical appraisal used the MMAT tool, and data synthesis followed SWiM standards for narrative synthesis.

Results: From a total of 258 papers initially identified, the final review included 5 studies conducted in the USA, comprising 2 cross-sectional, 2 cohort, and 1 longitudinal study. Four studies explored the bivariate association between discrimination, trust, and adherence, finding significant inverse relationships between discrimination and adherence. Trust showed a positive association with adherence levels and an inverse relationship with discrimination. All 5 studies investigated the mediation effect of trust between discrimination and adherence, indicating that trust mediated a significant portion of the association between discrimination and adherence across studies.

Summary/Conclusion: The findings shed light on key considerations for improving medication/treatment adherence among global majority individuals with chronic illnesses, such as SCD, by addressing the impact of discrimination on trust. Our results underscore the pivotal role of trust as a mediator in the relationship between discrimination and adherence. Moving forward, leveraging these insights can inform the development of targeted interventions to improve healthcare outcomes for marginalised populations. By prioritising trust-building strategies within healthcare systems and advancing culturally competent care, future initiatives can effectively address healthcare disparities and ensure equitable standards of healthcare services and improve treatment outcomes.

1. Hosseinabadi-Farahani et al. Pakistan Journal of Medical & Health Sciences, 2021; 14.

2. Hamed et al. BMC Public Health, 2022; 22, 13122.

3. Williams et al. Annual Review of Public Health, 2019; 40, 105.

4. Paradies et al. PLOS ONE, 2015; 10, 1.

5. Togioka et al. PubMed StatPearls Publishing; 2023.

6. Haywood et al. Journal of General Internal Medicine, 2014; 29, 1657.

7. Cuffee et al. The American Journal of Public Health, 2013; 103, e55.

Topic: 006–Health services and outcomes research including psychology

H.F.C. Chen¹, L.C. Chavez¹, S.E.C. Creary¹

Nationwide Children's Hospital Research Institute¹

Background: Multiple studies have highlighted the sustained gaps in receipt of prophylactic antibiotics and stroke screening among youth with severe sickle cell disease (SCD) in the United States (US), a primarily underrepresented minority and high-risk population.^1–3 However, biannual hematology clinic visits (HCV) and annual well-child visits (WCV) are also recommended for all youth with SCD^4,5 and are opportunities to provide these services, as well as other preventive care. Yet, data through the mid-2010s suggest that only 40% of youth with SCD had an annual HCV⁶ and only 53% had an annual WCV.⁷ If these gaps persist, they would point to continued missed opportunities to deliver preventive care to a vulnerable population.

Aims: The aims of this study were to describe WCV and HCV adherence in a contemporary cohort of youth with SCD and to explore their visit adherence over time.

Methods: This retrospective, Institutional Review Board-approved, cohort study had a waiver of consent to use Medicaid claims data (2019–2021) from Partners for Kids (PFK). PFK is a pediatric Accountable Care Organization for Medicaid-enrolled (e.g., publicly insured) youth in Ohio in the US. Youth were included if they were aged 3-17 years in 2019, enrolled in Medicaid for ≥11 months each calendar year, and had ≥3 insurance claims with a SCD diagnosis code during the study.⁸ Adherence to WCV was defined as ≥1 outpatient claim with a primary care provider and documentation of well-care based on insurance diagnostic or procedure codes during the calendar year.⁹ Adherence to HCV was defined as ≥2 outpatient visits with a hematology specialist with an claim including a SCD diagnosis code. Each year, youth were categorized as: adherent to WCV and HCV (group 1), having a WCV and/or HCV, but not the recommended frequency (group 2), and no WCV or HCV (group 3).

Results: A total of 160 youth with SCD were included with a mean age of 9.2 years (SD = 3.8). In 2019, 48% had a WCV and 45% had ≥2 HCV.

From 2019–2021, 18%–22% of youth received recommended WCV and HCV (group 1), but 19%–24% did not have either of these visits. In 2020, 53% remained in the same adherence group as 2019, and in 2021, 58% remained in the same adherence group as 2020. In addition, 35% remained in the same group all three years, including 18% of group 1.

Conclusion: In a contemporary cohort of publicly insured youth with SCD in the US, preventive visit adherence remained abysmally low. These findings may provide some explanation for why receipt of prophylactic antibiotics and stroke screening are also unchanged,^1-3 since these cannot be provided without visits. Thus, quality improvement initiatives for these indicators may continue to stagnate without active outreach to engage these youth into care.

Adherence patterns identified potential missed opportunities for intervention. For instance, approximately one fourth of youth did not have either a WCV or HCV, limiting the ability to deliver recommended care. Thus, interventions to address access barriers may need to come first. With heightened awareness that addressing social needs optimizes patient outcomes,¹⁰ there may be opportunities for public insurers to focus on social needs related to receipt of care, such as transportation barriers. Our findings also suggest a potential silver lining—relatively few became less adherent the subsequent year, suggesting that once youth are connected to care they may stay engaged.

There are limitations to acknowledge. First, our results may not be generalizable. Second, we were unable to evaluate SCD severity which could impact visit adherence. Finally, preventive visits early in 2020 may have been cancelled due to the COVID-19 pandemic, but there was not a substantial decline in adherence in 2020, suggesting that youth may have “caught up” later in 2020.

Summary: Preventive visit gaps for youth with SCD in the US persist into the 2020s and may explain our failures to provide quality care to these vulnerable youth. Initiatives that address visit adherence may have potential to improve care across multiple indicators.

Topic: 006–Health services and outcomes research including psychology

S. Singh¹, E. Young², R. Jolley², V. Garcia², M. Mathews², R. Auturally², J. Phizacklia², M. Besser²

University of Cambridge¹, Addenbrooke's Hospital²

Background: Individuals with sickle cell disease (SCD) seek hospital care most frequently for pain crises. Sickle cell crisis is a serious consequence of sickle cell disease characterized by intense pain and tissue ischemia that requires immediate medical attention. The NICE guideline CG143 underlines that patients should receive analgesia within 30 min of arriving at the emergency department (A&E). Patients should be treated as experts in pain management for their SCD, however, the “No One's listening report” has shown major gaps. Not all areas within A&E are suitable for safe administration of parenteral opiates, resource constraints caused long delays for all patients between triage and specialised service areas. We defined areas safe for administration as “feasible treatment location.”

Aims: To evaluate the annual performance of acute sickle cell pain crisis management at Cambridge University Hospital (CUH) and compare it to the previous 12 months. Exploration of barriers to deliver care in accordance with CG143 standards.

Methods: The audit included a retrospective review of three key datasets: (1) Time from arrival to opiate delivery (2) Time from arrival to reach a feasible treatment location within the Addenbrooke's hospital, and (3) Percentage of CG143 recommendations met. In addition, exploratory analyses of the effect of time of day of presentation on (1), (2), and (3) were also performed. Data from CUH hospital records were collected from 01/04/2023 to 01/04/2024 and analyzed.

Results: In a population of 116 patients (16–78 years old) with SCD, for the time-period analyzed, there were 40 admissions (23 female, 17 male) in 26 patients (17 female, 9 male) with SCD, of which 6 patients had multiple admissions (In 2022: 32 admissions in 27 patients). After auditing CUH performance against the NICE CG143 standards, it was found that 2 out of 40 relevant admissions (5%) received immediate pain relief within 30 minutes of presentation. In comparison, 5 out of 29 (17%) relevant admissions to CUH in 2022 received pain relief within 30 min. The median time from arrival to analgesia was 81 min in 2023 with an interquartile range (IQR) of 78 minutes (In 2022: median time = 60 min, IQR = 51.5 min).

The median time from arrival to a feasible treatment location within CUH in 2023 was 127 minutes with the IQR of 360.5 minutes. Furthermore, on average 86% of the CG143 recommendations were met on the admissions reviewed. 5 out of 40 (12.5%) had psychologist review during the admission.

Of 10 extreme outliers in time from arrival to opiate administration (120-344 minutes), 8 occurred outside core hours (9.00–17.00).

Summary: Frequent painful crises are related to psychological difficulties and low engagement in routine everyday activities. Time of day of patient presentation to a general A&E is also likely to affect the quality of specialist care delivered to the patient. The audit found considerable variations from year to year in the prompt administration of pain treatment to patients presenting to the hospital with acute sickle cell pain crises. While the NICE CG143 guidelines recommend providing analgesics within 30 minutes of arrival, the American Hematology Society proposes a more permissive timeframe of 1h. Meeting the existing NICE recommendations is difficult due to a variety of factors influencing pain relief administration, such as waiting times and A&E staffing levels, and the ASH guidance may provide a more practical approach.

Topic: 006–Health services and outcomes research including psychology

S.P. Hibbs¹, A. Gaspar², Y. Hendricks², M. Shaniqua³, P. Telfer⁴, S. Paparini¹, D. Swinglehurst¹

Wolfson Institute of Population Health, Queen Mary University of London¹, Barts Health NHS Trust², Barking, Havering and Redbridge NHS Trust³, Blizard Institute, Queen Mary University of London⁴

Background: The acute painful crisis (APC) is the most frequent complication of sickle cell disease (SCD). Several decades of advocacy, research and clinical guidelines have highlighted the need for rapid analgesia as key to good crisis care.¹ Healthcare-related stigma contributes to pain experience during crisis episodes in hospital, in addition to biological factors.² If other elements of suffering—beyond pain alone—are facets of acute painful crises, recognition of these may open additional strategies of care alongside more effective treatment of pain.

Aims: To illuminate what constitutes good hospital care for people experiencing sickle cell crisis, and avenues to achieve this.

Methods: Exploring Practices of Care for Sickle Cell Crises (EPOC4) is a multi-site ethnographic case study of adult sickle cell crisis care in East London (UK). To date, the lead researcher (SPH) has undertaken (a) 11 in-depth interviews with six patient participants (b) 28 sessions of observations of care and informal clinician interviews across emergency departments, wards, and ambulatory units at three hospital sites. Informed consent was received from all participants.

The approach of “accompaniment” in healthcare was developed by liberation theologians and applied to patients with infectious diseases by the physician-anthropologist Paul Farmer. “Accompaniment” provides a lens to understand how wider elements of suffering could be approached by clinicians.³

Results: In addition to pain, patient participants highlight several other forms of suffering during crises. Several patients describe the fear of dying during their journey to hospital or in the early stages of a crisis (even when these crises may look “uncomplicated” to clinicians). The interruption to plans and commitments that crises impose upon people with SCD creates suffering through guilt (e.g., letting down others) and anxiety (e.g., fulfilling caring commitments during crises or sensing the accumulation of additional responsibilities during the crisis period). Some patients highlight a loss of dignity during crises: the reliance on others for washing, dressing and using the toilet; intrusive questions and examinations from clinical teams; and inappropriately public spaces for emergency sickle cell care. These and other elements of suffering during crises are not articulated or addressed by existing clinical guidelines.¹

Examples of good care during crises shared by patients include but go beyond timely pain relief: these encounters affirm individual personhood; celebrate life events that crises have interrupted; and build personal connection and trust between patients and individual clinicians.

Conclusion: For patient advocates, this approach may suggest new ways to articulate their knowledge of crises and care to other patients, clinicians, and policy makers. For non-specialist clinicians, awareness of these broader aspects of suffering may foster empathy and connection with patients. For sickle cell specialists, the lens of accompaniment may give words to positive approaches they already use, and illuminate other possibilities.

1. Acute Painful Episodes in Hospital | Guidance | NICE. NICE; 2012. Accessed July 14, 2023. https://www.nice.org.uk/guidance/cg143

2. D Bulgin et al. Stigma and quality of life in adults with sickle cell disease in Jamaica and the United States. Psychology, Health and Medicine, 2023; 28(5), 1133-1147. doi:10.1080/13548506.2021.2019808

3. P Farmer. To Repair the World: Paul Farmer Speaks to the Next Generation. (Weigel JL, ed.); 2019.

Topic: 006–Health services and outcomes research including psychology

K.A. Amegan-Aho¹, I.D. Baah¹, R. Bruku², M.A. Ampomah³

Department of Paediatrics and Child Health, School of Medicine, University of Health and Allied Sciences¹, Department of Internal Medicine, Ho Teaching Hospital², Department of Family and Community Health, Fred N. Binka School of Public Health, University of Health and Allied Sciences³

Background: Regular attendance at sickle cell clinics is crucial for enhancing the quality of life in patients with sickle cell disease (SCD). However, in Ghana, the attendance patterns and influencing factors remain unknown, hindering the development of targeted healthcare improvements.

Aims: To determine attendance patterns over 12 months, and identify patients-, caregivers-, and health systems-related factors regarding routine clinics in two major hospitals in the Volta Region, Ghana.

Methods: This cross-sectional study involved caregivers of children and adolescents aged 0 to 17 years with SCD who were registered at the sickle cell clinics of Ho Teaching Hospital and Volta Regional Hospital in the Volta Region, Ghana. Ethical approval and informed consent were obtained before interviewing caregivers using a semi-structured questionnaire from June to August 2023.

Results: A total of 72 caregivers were interviewed, of which 61 (84.7%) were females. The majority (54; 75.0%) of these caregivers were mothers of the patients with SCD. The mean age of the patients with SCD was 9.19 ± 4.9 years; the majority (40; 55.6%) were female, and 58 (80.6%) had hemoglobin SS while 14 (19.4%) had SC. The median age at first sickle cell clinic enrolment was 3.0 years [IQR: 1.9–6.1] and the median duration of follow-up was 3.2 years [IQR: 1.7–7.0]. Most patients (50; 69.4%) had missed clinic appointment at least once in the previous 12 months. The main reasons for missed appointment were health system-related, caregiver-related, and patient-related (Figure). Univariate analysis showed no significant association between caregivers' characteristics and the likelihood of their child missing clinic appointment. Patients-related factors significantly associated with missed appointment were age (p = 0.003), and educational level (p < 0.001).

Conclusion: The proportion of missed clinic appointment was high in the population studied. Community-based support programs and social services are needed to assist families with SCD in the Volta Region. Additionally, issues related to clinic space, privacy, waiting times, and better access to hydroxyurea should be addressed to enhance the routine care provided to patients with SCD.

1. Masamu et al. BMC Health Services Research 2020; 20, 1141.

Topic: 006–Health services and outcomes research including psychology

L. Tunji-Ajayi¹

Global Action Network for Sickle Cell and Other Inherited Blood Disorders¹

Background: The Global Action Network for Sickle Cell and Other Inherited Blood Disorders (GANSID) is a global network of 60+ patient organizations in 20 countries, comprising healthcare providers, health organizations, researchers, professional and academic societies, and industry partners that serve patients and families affected by Sickle Cell Disease (SCD), Thalassemia and other inherited blood disorders. As a worldwide presence, GANSID facilitates collaboration among diverse stakeholders to empower local, national, and regional organizations in improving outcomes for affected individuals.

Aims: In this presentation, we discuss the role of international advocacy in addressing complex challenges and driving better outcomes for those affected by SCD and inherited blood disorders, with a spotlight on GANSID's novel approach to uniting patient organizations globally.

Methods: Through a regional network model with a special focus on underserved areas, GANSID advances education, research, cross-disease collaboration, advocacy initiatives, and policy development to elevate the lives of families impacted by SCD and other inherited blood disorders.

Results: By the end of the presentation, participants will be able to build upon the insights gained from the GANSID advocacy model and leave with constructive strategies for advancing international advocacy initiatives aimed at enhancing patient outcomes.

Conclusion: Individuals and families affected by SCD and other inherited blood disorders represent a demographic with multifaceted needs, posing a significant global challenge to healthcare systems worldwide. Cross-disease collaboration among advocacy organizations can bridge gaps and provide access to the opportunities and resources necessary for effective advocacy, ultimately improving outcomes for individuals within this population.

1. https://inheritedblooddisorders.world/

Topic: 006–Health services and outcomes research including psychology

P. Olubori¹, J. Enoch², R. Awadzi¹, C. Taylor³, A. Ghulakhszian¹, C. Dinah¹

Central Middlesex Hospital, London Northwest University Healthcare Trust¹, City, University of London², Unsickle My Cells³

Background: Sickle cell retinopathy (SCR) is a complication of sickle cell disease (SCD) that can result in significant temporary or permanent vision loss. In SCR, abnormal blood vessels grow on the retina, which can bleed or ultimately detach the retina from the eye wall, leading to retinal damage and vision loss. The unwanted blood vessels may also shrink away on their own. Due to the lack of high-quality evidence on treating SCR, ophthalmologists may be uncertain about the benefits of a cautious “wait-and-see” approach, versus proactive interventions like laser photocoagulation, for stage 3 SCR. If SCR subsequently worsens to stage 4 (vitreous haemorrhage) or stage 5 (retinal detachment), then vitrectomy, a surgical intervention, is required; however, even post-surgery, functional vision generally remains poor. Therefore, earlier detection of SCR may help prevent significant vision loss.

Aims: Although SCR is believed to affect quality of life, psychosocial studies to date have focused on SCD patients' knowledge and awareness of SCR, rather than their lived experiences. Furthermore, no qualitative research has explored how clinicians manage and treat SCR amid limited guidance and low-quality evidence. In this qualitative study, we sought to: firstly, understand patient perspectives on SCR treatment and SCR's impact on vision-related quality of life; and secondly, explore clinician perspectives on current SCR management and their views on the advantages and challenges of screening for SCR.

Methods: The study included 12 patients with stage 3 or higher proliferative SCR and 8 clinicians with varying levels of experience in SCR care in the UK. One-to-one semi-structured interviews were conducted using MS Teams videoconferencing. Informed written consent was obtained from all participating patients and clinicians. The audio-recorded interview data were transcribed verbatim, and analysed using the Framework Method of analysis.

Results: Preliminary findings from patient interviews revealed significant impacts on driving and employment due to vision impairment. Patients reported a lack of clear, consistent information about SCR, which sometimes undermined trust in their eye care providers. Some patients felt that systemic racism contributed to poor outcomes and the neglect of SCR patients.

Clinicians' views on SCR screening were analysed using the Theoretical Domains Framework (Atkins et al., 2017). They discussed challenges such as the need for suitable imaging equipment, concerns about patient motivation to attend screenings, the lack of a clear pathway for SCR treatment if early-stage symptoms are detected, and the potential for SCR screening to cause patient anxiety. However, they also strongly believed that screening could prevent late-stage complications, and could also empower patients and provide a setting for sustained patient education.

Summary/Conclusion: Interim findings suggest that vision loss from SCR exacerbates the negative impact of SCD on quality of life, particularly in areas such as driving and employment. The lack of contemporary, high-quality evidence to underpin SCR treatment can undermine patient-physician relationships. Clinicians have justified concerns about SCR screening but also recognise potential benefits from early detection and patient empowerment. Although a small study with limited generalisability, strengths include in-depth insights into individuals' experiences of visual impairment due to SCR, and frontline professionals' perspectives of practicalities of SCR screening in the NHS. Further research is needed to evaluate contemporary interventions for SCR, cost-effective screening methods, and identifying the groups most at risk of SCR.

1. Atkins et al. Implementation Science, 2017; 12, 77.

Topic: 006–Health services and outcomes research including psychology

Y. Zhou¹, D. Dillon¹, E. Bryan¹, V. Garcia¹, R. Jolley¹, R. Auturally¹, M. Mathews¹, K. Langham¹, E. Young¹, M. Besser¹

Department of Haematology, Cambridge University Hospital Trust¹

Background: Bone involvement in sickle cell disease (SCD) is a source of chronic, progressive disability (Zanoni et al., 2015). Therefore, pain and functional limitations are common SCD complications. There are few direct studies on the impact of movement programmes in SCD patients, however, there is indirect evidence of benefit in improving pain control and functional disability from other conditions (Barker et al., 2014).

Hydrotherapy is defined as “a physiotherapy programme utilising the properties of water…specific for an individual to maximise function” (ATACP 2014). Buoyancy of hydrotherapy enables functional exercise with reduced gravity and improved muscle strength, yet there is limited literature of hydrotherapy in SCD.

Methods: Cohort 1 included a total of 8 female adult SCD patients with an average age of 44 years, who received 8 sessions of 30-min hydrotherapy at Cambridge University Hospital (CUH) led by 2 physiotherapists over 16 weeks. The participants registered their interest through a form on the local patient forum, and the cohort was decided based on facility capacity and abundance of female patients who signed up. Those who could not follow instructions or had active infection/ulcers were not included in this programme.

At the start and end of the programme, patients filled in a questionnaire on their current wellbeing and mobility, the ASCQ-Me short forms and the patient health questionnaire (PHQ-9). Patients also completed a final feedback survey.

Results: The numbers of participants in cohort 1 with the genotypes HbSS and HbSC were 6 (75%) and 2(25%) respectively. 4 participants had a previous diagnosis of avascular necrosis and 3 had a previous joint replacement. None of the participants were able to participate in all 8 hydrotherapy sessions.

All participants enjoyed the programme and would recommend it to others, particularly patients with “leg cramps” and “chronic pain.” Figure 1 shows a word cloud of participant responses to aspects they found the most beneficial. Key themes were “general wellbeing,” “getting exercise,” and “the social aspect.” 3 responses to the survey proposed “aftercare options” and “post-programme exercises” “all year round [particularly] in winter and the cold seasons.”

Limited difference in mobility/functionality was reflected in pre- and post-programme questionnaires, however verbal feedback from patients highlighted the perceived benefit only seemed to have outweighed the physical exhaustion after 2 sessions. Only 4 out of the 8 participants felt confident enough to access local pools independently at the end of the programme and the main apprehension highlighted was fear of a crisis in line with previous studies highlighting fear of pain and fatigue as main barriers to physical activity in SCD (Olorunyomi et al., 2022).

During an ongoing second cohort of patients receiving hydrotherapy, challenges we are encountering include poor attendance and poor engagement in surveys.

Summary: Hydrotherapy may be beneficial for adults with SCD. However, challenges include overcoming patients' fear of a pain crisis and encouraging participation.

Topic: 006–Health services and outcomes research including psychology

M.A. Abboud¹, M.B.Z. Bou Zerdan¹, S.N.Y. Yazbek¹

American University of Beirut¹

Introduction: Sickle cell disease (SCD) is a genetic disorder characterized by crescent shaped red blood cells that can lead to various health complications. In resource constrained world countries with high rates of consanguinity, a higher prevalence of genetic disease, such as SCD, can be observed. This poses significant challenges for both the affected individuals and the healthcare system. This study aims at assessing the needs of patients and healthcare workers involved in SCD management on the one hand, as well as the amenities and organization of centers that manage SCD patients on the other. As part of a broader undertaking, the target is to identify service deficiencies and enhance the level of care provided.

Methods: Patients, parents, or legally designated representatives were asked to complete questionnaires on different aspects of the care they have been provided spanning the time of diagnosis till present. These were then safeguarded by the investigators for analysis. In addition, an electronic questionnaire was sent to reference persons of healthcare facilities across resource constrained countries with high refugee rate to analyze the services provided, equipment available, and number of staffs. Data were analyzed by the coordinating investigator using SPSS and thematic analysis.

Results: Patients consistently reported dissatisfaction with the quality of care, highlighting various deficiencies in their healthcare experiences. This was particularly pronounced among rural residents, who encountered greater obstacles in accessing high-quality medical services compared to those living in urban areas with p < 0.001. This disparity underscores the urgent need for targeted enhancements in healthcare accessibility across different geographic locations. In contrast, healthcare facilities grappled with issues of understaffing (p = 0.001) and limited resources, hampering their ability to provide comprehensive care for individuals with sickle cell disease. Additionally, inadequate training (p = 0.033 for the use of infection screening tools) to address the unique challenges posed by sickle cell disease further compounded the challenges faced by both healthcare providers and patients seeking specialized care.

Conclusion: The study uncovers substantial deficiencies in the quality of sickle cell disease management. The highlighted inadequacies underscore the pressing requirement for systematic enhancements. Collaborative endeavors to address these gaps would yield substantial benefits for both patients and healthcare establishments. Addressing these concerns has the potential to elevate the overall standard of care, guaranteeing that individuals afflicted by sickle cell disease obtain the necessary attention and assistance.

Topic: 006–Health services and outcomes research including psychology

A.M. Mande¹, L.R. Ruggieri², A.I. Abdulakadir³, F.B. Bonifazi², R.C. Conte², A.D. Didio², M.F. Faleye¹, A.H. Hassan³, M.A.I. Muhammad¹, R.A.M. Aliyu³, H.R.A. Rufai³

ABUTH¹, FGB², ABU³

Background: Nigeria is known to have the highest burden of sickle cell disease (SCD) in the world and this calls for an urgent need for policies for the prevention and management of SCD. Recent small-scale epidemiological studies in the country have shown a high frequency of HbS and other associated haemoglobin genetic mutations like β-Thalassaemia, prompting the need for larger epidemiological research. This study has been conducted within the African Research and Innovative Initiative for Sickle Cell Education (ARISE) that has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 824021.

Aims: To design and implement communication materials for SCD education, prevention, and control.

Methods: We designed leaflets, hand-outs, and question and answer book about SCD in English and translated them to the Hausa language, the most popular language in northern Nigeria. The materials explain in simple language and using infographics what is SCD, the types of SCD, how it is inherited, who is affected, health problems associated with it, SCD in pregnancy, newborn screening, prevention, control, and management.

Results: Over two thousand patients, parents, caregivers, and the public were issued copies of the hand-outs and the leaflets in Ahmadu Bello University Teaching Hospital in Zaria, Nigeria, and across many primary healthcare facilities in Zaria in the period 2020 to 2023. 1584 samples were analysed for NBS in 3 years: 2021 to 2023. Zero babies were diagnosed in 2020.

Conclusion: communication for SCD education, prevention, and control is a veritable tool to reduce the disease burden, mortality, and morbidity.

This study has been conducted within the African Research and Innovative initiative for Sickle cell Education (ARISE) that has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 824021.

Topic: 006–Health services and outcomes research including psychology

K. Obadiah¹, D. Attah², M. Koelbel³, F.J. Kirkham⁴

Rural hospital Fadan Kagoma¹, Children's hospital², Klinik für Neurologie³, UCL GOSH Institute of Child Heal⁴

Background: Stroke is one of the common complications of SCD and a global burden as it is reported by WHO in 2019 to be the second leading cause of mortality and morbidity in the world. In recent years, the prevalence of stroke in the general population in Nigeria is 1 per 1000 while the 30 days fatality rate is as high as 40%. 1 in 3 survivors experience a stroke recurrence (Vincent & Adamu, 2019).

Children with SCD are at high risk of stroke. The annual birth rate in SCD was estimated at 300,000 globally, Nigeria currently accounts for 100,000 annual births with SCD (33% of the global burden of SCD). Recent research conducted by a group of experts estimated that up to 150,000 infants will be born with sickle cell anaemia annually in Nigeria. Other African countries, including Kenya, Tanzania and Zambia, also have a high incidence of SCD births and therefore a large number of children at risk of stroke.

There is a peak stroke risk in children with around 10% of children experiencing stroke between their second and 16th birthdays if transcranial Doppler screening and prophylaxis with chronic transfusion or hydroxyurea are not available. Research shows that using the FAST mnemonic (Face, Arm, Speech, Time), children in the general population presenting with stroke the common symptoms of arm weakness (63%), facial weakness (62%), leg weakness (57%), speech disturbance (46%), and headache (64%). Presentation with seizures is also common in children experiencing stroke but is not part of the FAST mnemonic. It has been suggested that an extension to BE FAST ISH may raise awareness without being too cumbersome but there are few prospective data in populations of children at risk of stroke.

Primary stroke treatment and rehabilitation are typically delayed because of lack of awareness in the recognition of signs and symptoms and therefore delayed accessibility of hospital for emergency intervention with, for example, top-up or exchange transfusion to improve oxygen delivery to vulnerable brain tissue which may not have infarcted. There is also evidence that for first overt stroke in SCD, exchange transfusion, which can be manual or automated, is associated with a lower risk of recurrent stroke compared with simple top-up transfusion (Hulbert et al., 2006). Manual exchange transfusion is often available in African hospitals but delayed emergency treatment may lead to severe complications and permanent motor disability, epilepsy, and cognitive difficulties which will incapacitate the child and affect their future studies and work.

Initiating and applying the stroke recognition tools for early recognition of stroke may help families to spot the symptoms early and access urgent hospital intervention early so as to improve outcome, potentially turning a disabling stroke into a Reversible Ischemic Neurological Deficit (RIND) or Transient Ischaemic Attack (TIA). Appropriate treatment may also reduce the risk of recurrent stroke. This will be of great impact to Africa, because existing research shows that despite ongoing treatments and rehabilitations patients still experienced stroke recurrence.

Method: In consultation with other ARISE Secondees and Mentors, a review of systems used stroke recognition tools (FAST, BE-FAST, and BE-FAST-ISH) for public information has been undertaken and a first draft of an appropriate figure has been created to enable SCD patients and their families to recognise the early signs of stroke so that they can access healthcare quickly in Africa to enable rapid treatment allowing studies of time to and mode of treatment to improve outcome and reduce stroke recurrence.

Results: An appropriate recognition tool has been developed and will be piloted in August and September 2024 in Kenya, Zambia, and Nigeria through comparison of the use of the FAST, BE-FAST, and BEFAST-ISH stroke recognition tools with professional, patient, carer, and public feedback on the relative importance of picture and text translated in the local language.

Discussion: The increasing number of children being born with SCD means that there is likely to be an increase in the number of strokes in the near future. This calls for urgent public knowledge for early recognition of signs and symptoms of the public using the use of FAST, BE-FAST, and BEFAST-ISH stroke recognition tools to improve recognition and rapid hospital access for patients with SCD and stroke and to enable studies of treatment.

1. G Vincent-Onabajo, A Adamu. Puerto Rico Health Sciences Journal, 2019; 38, 181–184.

2. ML Hulbert et al. The Journal of Pediatrics, 2006; 149, 710–712.

Topic: 006–Health services and outcomes research including psychology

Z.A.K. Kuupah¹, I.O.O. Ogumbe²

University of Ghana¹, Strathmore University²

Background: Despite significant efforts to increase health expenditure, health outcomes have only marginally improved, raising concerns about the significance of health expenditure in improving health outcomes in Africa.

Objective: The objective of this research is to investigate the correlation between healthcare spending and health system outcomes in African nations.

Methods and Materials: The data for this study was extracted from world development indicators with a specific emphasis on the period from 2000 to 2020. The study investigates various factors including Birth Rate (BR), Life Expectancy (LE), Death Rate (DR), Fertility Rate (FR), Lifetime time risk (LR), Number of maternal mortality (NM), suicide mortalities (SM), Population Growth (PG), Domestic Government Health Expenditure (DGGHE), Current Health Expenditure (CHE), Domestic Private Health Expenditure (DPHE), Out-of-Pocket Expenditure (OPE), and External Health Expenditure (EHE). The data for this study were cleaned using Excel and missing data were removed using the R command omit data. The analysis was done using R software. The structural equation model was used as the statistical model to establish this relationship. The results of this study were presented using tables and graphs (figures). The research measured the effect of different categories of health expenditures on health outcomes by using a Poisson generalized regression model. The research included all African nations to provide a complete insight into the impact of financial investments in health on demographic and health indicators across the continent.

Preliminary Results: For each country, eight dependent variables (Birth Rate (BR), Life Expectancy (LE), Death Rate (DR), Fertility Rate (FR), Lifetime time risk (LR), Number of maternal mortality (NM), suicide mortalities (SM), and Population Growth (PG)) and five independent variables (Domestic Government Health Expenditure (DGGHE), Current Health Expenditure (CHE), Domestic Private Health Expenditure (DPHE), Out-of-Pocket Expenditure (OPE), and External Health Expenditure (EHE)) were used for the study. All variables were extracted from the same source ranging from 2000 to 2020. This study conducted an analysis using datasets that are accessible to the public. The location of this data can be found at: https://data.worldbank.org.

Conclusion: This study provides useful insights to the area of health economics and public health policy in Africa. It gives evidence-based suggestions for improving health outcomes by optimizing health spending. The results were shown and examined, emphasizing their significance for the next health funding approaches and policy measures.

1. OS Olatunde et al. Health expenditure and child health outcome in West Africa. International Journal of Social Sciences Perspectives, 2019; 5(2), 72–83.

2. M Kofi Boachie et al. Public health expenditures and health outcomes: new evidence from Ghana. Economies, 2018; 6(4), 58.

3. J Chireshe, MK Ocran. Health care expenditure and health outcomes in sub-Saharan African countries. African Development Review, 2020; 32(3), 349–361.

4. BE Owumi, A Eboh. An assessment of the contribution of healthcare expenditure to life expectancy at birth in Nigeria. Journal of Public Health, 2021; 1–9.

5. EY Sango-Coker, MA Bein. The impact of healthcare spending on life expectancy: evidence from selected West African countries. African Journal of Reproductive Health, 2018; 22(4), 64–71.

Topic: 006–Health services and outcomes research including psychology

E. Gani¹, G. Ozongbe Joel², T. Hadiza Mohammed¹, U. Tanimu Deborah ³

Kaduna State University Library¹, Panaf International School, Kaduna², Kaduna State ministry of Education³

This study explores the potential of Artificial Intelligence (AI) to improve Sickle Cell Disease (SCD) healthcare in Nigeria. With a high SCD burden and limited access to healthcare, Nigeria urgently needs innovative solutions. The research reviewed data from ten Nigerian hospitals, revealing extensive use of Information and Communication Technologies (ICT) for SCD management, but limited adoption of AI. The authors propose AI solutions like medical image analysis, patient data management, and predictive modeling to enhance diagnosis and treatment. The study emphasizes the potential of AI for personalized medicine, tailoring treatment plans to individual patients rather than relying solely on symptoms. This aligns with the growing role of AI in precision medicine, particularly for genetic disorders like SCD.

Background: Sickle cell disease (SCD) (Isa et al., 2020; Nnodu et al., 2021) is a debilitating inherited blood disorder affecting millions globally, with Nigeria bearing the heaviest burden. Roughly 150,000 births annually in Nigeria are affected by SCD (Inah et al., 2021), highlighting the urgent need for innovative solutions to improve early diagnosis and treatment for those living with the disease.

Early diagnosis (Terna & Ufelle, 2021) and treatment of complications in Nigerians with sickle cell disease (SCD) face significant hurdles due to limited access to healthcare (Gouda et al., 2019), especially in rural areas. This leads to delayed diagnosis, as many only seek medical attention during painful crises. shortage of specialized healthcare professionals and diagnostic equipment, along with high medication costs, further compromises proper care, resulting in poorer health outcomes and quality of life for Nigerians with SCD.

Aim: The study was conducted in Nigeria to investigate methods for SCD healthcare delivery through the application of AI.

Methods: With the focus on collecting data on the existing resources on AI-powered SCD healthcare services, ten hospital websites were reviewed. The hospital comprises public and private hospitals in different parts of the country. Data was obtained online from the websites of National Hospital Abuja (NHA) Ahmadu Bello University Teaching Hospital (ABUTH), University College Ibadan (UCI), Babcock University Teaching Hospital (BUTH), Lagos State University Teaching Hospitals, Seventh-day Adventist Hospital, Ile-Ife, Shouldice Hospital, Abubakar Tafawa Balewa Teaching Hospital (ATBUTH), St. Nicholas Hospital, Lagos and University of Nigeria Teaching Hospital (UNTH), Enugu (Mbunge & Batani, 2023). The data was evaluated thematically, and the evolving nature of AI-powered healthcare services may limit the findings' applicability over time.

Results: The findings revealed that all ten hospitals are utilizing ICT tools to provide SCD healthcare services (Akaba et al., 2023; Mbunge & Batani, 2023); which include Electronic Medical Systems, Mobile health (mHealth), Smart treatment, and Telemedicine. There is nothing to write home about utilizing AI tools (Elendu et al., 2023) despite their usefulness in providing SCD healthcare services with precision, error-reduction ability, and prediction of clinical outcomes (Akaba et al., 2023).

Summary: AI-powered tools that could be applicable for SCD in Nigeria are AI-based analysis of medical images analysis (Adigwe et al., 2024), AI algorithms to analyze X-rays (Adejumo et al., 2023), CT scans, and also MRI scans. Machine language tracks patient data to monitor medical history and predict the likelihood of future crises. Image Analysis predictive modeling, Chatbots, virtual assistants, and decision support assistants (Adejumo et al., 2023; Balogun et al., 2023). Chatbots and Virtual Assistants would answer frequently asked questions (Townsend et al., 2023). Leveraging these AI tools in Nigeria could importantly improve early diagnosis and treatment of SCD complications.

Conclusion: Individualizing medicine to each patient instead of according to symptoms signifies the importance of artificial intelligence. It has been shown that artificial intelligence will play an important role as one of the pillars of modern medicine as we move towards precision medicine, especially in genetic diseases like SCD.

Topic: 006–Health services and outcomes research including psychology

E. Owino¹, F. Okinyi², M. Liru³, C. Tenge⁴, B. Sorre³, M. Nangami³, M. Shilabula³

Sickle Cell Uhuru Trust (SCUT)¹, Nairobi University², Moi University³, Eldoret⁴

Background: Persons Living with Sickle Cell Disease (PLWSCD) have a chronic illness which requires proper diagnosis, lifelong medications, and follow up. They experience acute and chronic complications and are prone to frequent admissions and to receiving multiple blood transfusions. Description of their experiences can assist relevant authorities and stakeholders understand their plight and plan for their care.

Objective: To describe the lived experiences of PLWSCD in accessing medical care in 5 counties (Bungoma, Busia, Kakamega, Vihiga, and Trans-Nzoia) in Western Kenya.

Methods: A cross-sectional study was carried out between January to April 2022 in which interviewer administered questionnaires were used to collect information on the demographic characteristics, mode of diagnosis, frequency of hospital admissions and blood transfusions, and access to the standard medications required.

Results: A total of 2056 PLWSCD participated. Those aged <5 years were 816 (39.6%), 5–18 years were 929 (45.2%) and >18 years were 311 (15.1%). SCD was diagnosed by confirmatory tests (HPLC/HB Electrophoresis) in 357 (17.3%), screening tests (sickling test) in 1500 (73.0%) and clinically only in 199 (9.7%) PLWSCD. Those ever admitted were 1773 (86.2%) with 868 (49.0%), 564 (31.8%) and 34 (19.2%) admitted less than 5 times, 5 to 9 times, and more than 10 times respectively. PLWSCD ever transfused were 1645 (92.8%) with 838 (50.9%), 503 (30.6%), and 304 (18.5%) transfused <5 times, 5 to 9 times and >10 times respectively. A total of 1934(94.1%) had not received pneumococcal and meningococcal vaccines. Only 633 (30.7%) could access hydroxyurea regularly. A total of 1354(65.9%) had no beneficial medical insurance and therefore had to settle their bills from out of pocket.

Conclusion: Majority of PLWSCD experience frequent hospital admissions and receive multiple blood transfusions. Majority are not able to access and afford the required standard care.

Recommendations: The relevant authorities and stakeholder should ensure PLWSCD receive standard care. Families of PLWSCD should be encouraged to have a medical insurance.

1. Osunkwo et al. Hematology, 2020; (1), 562–569.

2. Milner et al. The New England Journal of Medicine, 1991; 325(21), 1476–1481.

3. Mapp et al. Nature Reviews Rheumatology, 2012; 8(7), 390–398.

4. Park et al. Blood, 2020; 135(23), 2071–2084.

5. Deuis et al. Frontiers in Molecular Neuroscience, 2017; 10, 284.

Topics: 001–Basic and translational

M. Di Mauro¹, G. Ceglie¹, G. Palumbo¹, M. Algeri¹, D. Rees², J. Brewin², S. El Hoss³

Department of Pediatric Hematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS¹, Department of Haematological Medicine, King's College Hospital², Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, Université Paris Cité³

Background: Ineffective erythropoiesis (IE) is the suboptimal production of mature red blood cells (RBCs) from an active marrow. Using both in vitro and in vivo models, high rates of apoptosis was detected during the terminal stages of erythropoiesis in sickle cell disease (SCD), suggesting a degree of IE exists in SCD (PMID: 32855279). Recently, we developed a novel index of ineffective erythropoiesis (IoIE) to quantitate IE and facilitate the comparison between patients (PMID: 34670360).

Aims: In this study, we applied the IoIE to a paediatric cohort. We evaluated the extent of IE in children with HbSS or HbSβ0 genotype compared to children with no haematological disorder and those with known IE. Within the SCD cohort we investigated the effects of therapy on this index.

Methods: Clinical and laboratory data were collected from the electronic patient record system at Bambino Gesù Hospital (Rome, Italy) (June 2021 to September 2023). The study was conducted under the declaration of Helsinki with the approval of the medical ethics committee. Blood tests were performed in the outpatient setting. Patients included were either on hydroxyurea (HU) stable dosing for at least 3 months, on regular blood transfusions, or not treated. Using soluble transferrin receptor (sTfR) as a measure of erythropoietic activity, and absolute reticulocyte count (ARC) as an indicator of bone marrow (BM) output, we calculated the IoIE as a way of quantifying IE. Patients included in the study were (i) SCD children (n = 49, median age 9 years, 45% female, 39 HbSS and 10 HbSβ0), (ii) β-thalassemia patients (known to have very high levels of IE, n = 29, median age 8 years, 52% female) and an (iii) control group (without RBC or BM disorders, n = 30, median age 8.5 years, 50% female). We compared our pediatric cohort with an adult cohort (n = 178, median age was 29.5 years, 57% female) from King's College Hospital (London, UK). Data were analyzed using the MannWhitney unpaired test.

Results: We established a normal range of IoIE using the control (0.018 ± 0.006) and validated IoIE in the cohort of patients with β-thalassemia, that had high IoIE levels (median IoIE: 0.11). The IoIE was slightly but not significantly elevated in SCD children (IoIE: 0.021, p 0.1) compared to age-matched control group (Figure 1A). In the adult SCD population, the IoIE value was significantly higher when compared children (Adult IoIE: 0.024; p 0.0017) (Figure 1A) suggesting that IE develops with age in SCD patients. Moreover, in our pediatric cohort, we evaluated IoIE in 7 transfused, 21 HU-treated, and 7 untreated patients. We confirmed that IoIE increased with HU and decreased with transfusions (p 0.007) (Figure 1B).

Conclusion: We have shown that IE does not seem to be significantly increased in children with SCD compared to controls. This contrasts with SCD adults in whom IE is increased, suggesting that IE in SCD is partly related to acquired damage to the BM niche, possibly by processes such as infarction, chronic ischemia, inflammation, and oxidative stress. HU increases IE, and this may be one way in which it increases HbF levels, through increasing selection of HbF-containing cells. In contrast, regular blood transfusions decrease IE in SCD, possibly by improving the dysfunctional BM microenvironment. Overall, IoIE seems to be a useful tool, and monitoring this index may be helpful in assessing response to HU, transfusions, and other therapeutic approaches. More generally, understanding of BM activity in SCD might offer opportunities to better comprehend the clinical heterogeneity of patients and optimize treatment approaches.

1. S. El Hoss et al. Fetal hemoglobin rescues ineffective erythropoiesis in sickle cell disease. Haematologica, 2021; 106(10), 2707–2719.

2. J. Brewin et al. A novel index to evaluate ineffective erythropoiesis in hematological diseases offers insights into sickle cell disease. Haematologica, 2022; 107(1), 338–341.

Topics: 006–Health services and outcomes research including psychology

D.D. Dwomoh¹, D.N.Y. Abankwah¹, A.B.A. Benneh-Akwasi Kuma¹, J.M. Spector², J.Q. Quartey¹, O.A. Egbujo³, K.M. Marfo³, S.F.O. Fiifi Ofori-Acquah⁴, J.N. Nonvignon¹

University of Ghana¹, Novartis Biomedical Research², Novartis Pharmaceuticals Corporation³, Sickle Cell Foundation of Ghana⁴

Background: Sickle cell disease (SCD) affects millions of people worldwide, with nearly 80% of the global burden incurred in sub-Saharan Africa (SSA).¹ As part of a public-private partnership to address SCD in Ghana, a multi-faceted health systems strengthening programme was implemented that included novel digital applications (“Apps”) to support newborn screening (NBS) data management and clinical use of hydroxyurea (HU). The Apps were designed according to inputs received by clinicians (physicians, nurses, and pharmacists) and patients in Ghana to address local needs and were engineered by an mHealth company (Dimagi) that specialises in customisable digital tools for use in low-resource settings.

Aims: This analysis evaluated utilisation, benefits, and challenges associated with NBS and HU management Apps among healthcare workers in Ghana.

Methods: This evaluation is part of a mixed-method monitoring and evaluation (M&E) study involving quantitative and qualitative research designs.² Healthcare professionals (HCPs) who used the Apps were interviewed. Questionnaires and tools were used to assess satisfaction, challenges, relevance, ease of use, and other relevant parameters for both Apps using a 5-point Likert scale (with “5” corresponding to the most positive assessment). The efficiency and impact of the Apps were determined using indicators such as time spent with patients, patients' length of stay at healthcare centres, time/effort of result distribution and tracking, and more. Data were analysed using appropriate statistical methods.

Results: Overall, 57 in-depth interviews of HCPs were conducted (Figure 1A). Their mean (range) age was 36.4 (24–55) years, and, on average, they worked for 4 years in the SCD units. Nearly half of the HCPs interviewed had heard about the NBS App, 7% were trained to use it, and <5% were actively using it at the time of the survey; 52% had heard about the HU App, of which 63% were trained to use it and 65% used it. Using the NBS App allowed for data aggregation and direct communication among personnel across birth centres, laboratories, regional programme coordinating centres, and SCD counsellors. Users of the NBS App felt strongly (mean score, 4.4) that the App was useful for their healthcare practice and helped HCPs to manage their patient's health effectively. Additional observed benefits of the NBS App included the timely availability of screening results facilitating informed decision-making for both HCPs and parents and easy access, transfer, and retrieval of records. The mean scores for both Apps were nearly 4.0 or higher for ease of learning to use the App, improved ability to deliver healthcare services, and improved communication/interaction with patients (Figure 1B). Reported challenges included an extended data entry process (for the HU management App), limited duration of data storage, and difficulties in synchronising data during poor internet connectivity. Nonetheless, most HCPs expressed acceptance of the Apps and highlighted their ease of use.

Conclusion: Digital Apps were reported to be user-friendly and associated with improved efficiencies compared with traditional paper-based chart records. Continued inclusion of these Apps as part of routine clinical care processes in Ghana may help to support optimized patient management. Of note, use of the NBS App is currently being expanded to multiple countries in Africa through a consortium organised through the American Society of Haematology.

1. GBD 2021 SCD collaborators. The Lancet Haematology, 2023; 10, e585–e599.

2. Moore et al. BMJ, 2015; 350, h1258.

Topics: 003–Clinical and epidemiological studies

I.M. Idris¹, A.A. Yusuf¹, I.I. Ismail¹, A.M. Borodo², S.A. Aji¹, A. Kuliya_Gwarzo¹, K. Mohammad¹, R. Alkassim³, N. Hussain⁴, M. Rodeghier⁵, A.L. Burnett⁶, M.R. DeBaun⁷

Aminu Kano Teaching Hospital¹, Kano², Aliko Dangote University³, Bayero University Kano⁴, Rodeghier Consulting⁵, Johns Hopkins University⁶, Vanderbilt University Medical Center⁷

Introduction: Recurrent ischemic priapism is a common complication of sickle cell anemia (SCA) shown to be driven by phosphodiesterase-5 (PDE5) dysfunction in a setting of relative nitric oxide deficiency.¹ All previously concluded trials for priapism prevention in SCA failed to show treatment efficacy.² Our trial focused on assessing the feasibility of conducting phase III for priapism prevention.

Methods: The trial was conducted at Aminu Kano Teaching Hospital (AKTH) and started recruitment on 13th Apr 2022. A Data Safety and Monitoring Board (DSMB) supervised the trial. We conducted a randomized, controlled, double-blind feasibility trial (N = 64) comparing tadalafil (PDE-5 inhibitor) plus hydroxyurea at 20 mg/kg/day (experimental arm) with hydroxyurea plus placebo (standard care arm) among men (18–40 years) with SCA, with at least three episodes of priapism in the past 12 months, to assess the recruitment, retention, and adherence (defined as monthly visits) rates as a feasibility outcome. The priapism data were obtained daily from the participants via replies to text messages and a monthly review of self-reported diaries during clinic visits.

All potential participants passed a screening phase (2–4 weeks). Randomization (1:1) was performed by a statistician using computer-generated numbers. The investigators, participants, and trial staff (except the pharmacist) were blinded to the treatment assignments. Secondary outcomes were priapism rate, duration, and pain intensity. We collected semen at baseline, exit, and 3 months after the participants stopped taking hydroxyurea to assess its effect on fertility. The IRBs of VUMC and AKTH approved the trial [Clinicaltrials.gov (NCT05142254) and the Pan African Clinical Trial Registry (PACTR202105561969346)].

Results: The DSMB met on 22nd May 2023 and stropped the trial due to futility based on the data locked as of 27th Feb 2023. The last participant exited the trial on 12th June 2023. Our trial achieved 100% recruitment, with retention and adherence rates for monthly visits of 98.6% and 97.4%, respectively. Adherence rates to tadalafil and hydroxyurea were 93% and 94%, respectively. Over a median of 10 months (3–12), 3.1 and 2.7 events per month were recorded in the experimental and standard care arms, with a rate ratio of 1.2; 95% CI: 0.5–2.8; p = 0.654. We noted a significant drop in priapism self-report after 4 months and elected to do post hoc analysis with only 4-month data. Post hoc, single-arm, pre-, and post-analysis limited to the 4 months of treatment compared to the screening period showed 46.3% rate reduction in the experimental arm (from 8.9 to 4.8 [difference 4.1; 95% CI: 1.6–6.6; p = 0.002]) and 50.5% rate reduction in the standard care arm (from 5.9 to 2.9 [difference 3.02; 95% CI: 0.6–5.4; p = 0.016]). The proportions of severe priapism pain dropped from 28.1% to 5.1% in the experimental arm (p < 0.001), and excruciating pain dropped from 25% to 0.9% (p < 0.001) in the standard care arm. The median priapism duration dropped in experimental (105 vs 60 min, p < 0.001) and standard care (60 vs 56, p < 0.001) arms. However, the rates of adverse events were similar.

Forty-one participants in the trial had seminal fluid analysis at baseline, exit, and 3 months after stopping hydroxyurea. Their median sperm concentration (millions/per mL) dropped at exit (66.6 vs 38.1, p = 0.047) but recovered 3 months after stopping hydroxyurea (38.1 vs 71.2, p = 0.003). The median progressive motility dropped at exit (11.6 vs 2.0, p = 0.027) but recovered 3 months after stopping hydroxyurea (2.0 vs 9.6, p = 0.002). A similar pattern was observed for nonprogressive motility and normal forms.

Conclusion: Hydroxyurea decreases the priapism rate by 50% compared to the baseline, with no difference between the tadalafil and hydroxyurea arms. Hydroxyurea at 20 mg/kg/day decreases sperm concentration and motility; however, there is complete recovery after hydroxyurea cessation for 3 months.

1. IM Idris et al. Hematology, 2022; 1, 450–458.

2. FI Chinegwundoh et al. Cochrane Database of Systematic Reviews, 2020; 4.

3. MR DeBaun, Expert Review of Hematology, 2014; 6, 767–773.

Topics: 006–Health services and outcomes research including psychology

M.A. Ampomah¹, A.H. Hood², F.J.K. Kirkham³, K.H.A. Amegan-Aho⁴

Department of Family and Community Health, Fred N. Binka School of Public Health, University of Health and Allied Sciences¹, University of Manchester, UK², University College of London, UK³, University of Health and Allied Sciences, Ho, Volta Region Ghana⁴

Background: Sickle cell disease (SCD) is a public health issue in Ghana, with approximately 2% of babies born with the condition annually.¹ Contemporary management involves comprehensive care to prevent complications, yet many children in Ghana do not fully benefit from such care due to late diagnosis and poor adherence to clinic appointments.^2,3 School-age children, in particular, are diagnosed late because of a lack of newborn screening, and may miss SCD clinic appointments frequently when clinic appointments conflict with their school schedule.^4,5 Existing literature on SCD school-based initiatives focuses more on SCD curriculum implementation, awareness creation, education of teachers, and education accommodations.^6,7 To maintain and improve the academic performance of these children, it is essential to manage SCD in the educational setting, especially where newborn screening is lacking, and there are a limited number of SCD clinics. This approach necessitates increased awareness, early diagnosis, and regular follow-up, but may improve attendance at clinic appointments and academic attainments.

Aims: To screen basic school children for SCD in the Volta Region of Ghana as part of the 2023 World SCD Celebration, and to discuss the implications and rationale for managing SCD within the educational setting.

Methods: A multistage sampling was used to select schools and pupils within the Hohoe Municipality, Volta Region, Ghana. Prior to the screening, a two-week educational campaign, comprising three sessions per day, was conducted in the communities of the selected schools. After obtaining approval from the education and health authorities, 10,000 consent forms were distributed to the guardians of the identified pupils. Pupils whose guardians consented were screened using haemoglobin electrophoresis between the 21st and 31st of August 2023.

Results: Of the 5000 identified pupils, 3390 (67.8%) from 71 public and private basic education schools (nursery to junior high schools) were screened. Among these pupils, 58.5% were female, with a mean age of 11.70 ± 3.04 years. The screening results were as follows: Hb SS (50; 1.5%), Hb SC (57; 1.7%), Hb CC (29; 0.9%), Hb AS (459; 13.5%), Hb AC (325; 9.6%), and Hb AA (2454; 72.4%). The prevalence of SCD (Hb SS and Hb SC) was 3.2%, with 107 pupils affected. Among the SCD-affected pupils, 57.0% were female, and the mean age was 11.64 ± 3.07 years. These findings, along with a proposal for establishing a school-based management program, are being discussed with the local educational and health authorities.

Conclusion: The prevalence of SCD among the basic school pupils screened is higher than previously reported in Ghana. Establishing a comprehensive school-based program to provide SCD services can bring the necessary care closer to the children and enhance the cooperation of school teachers, improving the health and academic outcomes of these pupils.

1. CI Segbefia et al. Implementing newborn screening for sickle cell disease in Korle Bu Teaching Hospital, Accra: Results and lessons learned. Pediatric Blood & Cancer, 2021; 68(7), e29068.

2. AM Sims et al. Diagnosis patterns of sickle cell disease in Ghana: a secondary analysis. BMC Public Health, 2021; 21: 1–7.

3. M de Montalembert. Sickle cell disease: a comprehensive program of care from birth. Hematology American Society of Hematology Education Program, 2019; 1, 490–495.

4. LE Crosby et al. School performance and disease interference in adolescents with sickle cell disease. Physical Disabilities: Education and Related Services, 2015; 34(1), 14.

5. N Haridasa et al. Student perspectives on managing sickle cell disease at school. Pediatric Blood & Cancer, 2019; 66(2), e27507.

6. EI Obeagu & GU Obeagu. Incorporating sickle cell disease curriculum in schools: an effective approach. Elite Journal of Health Science, 2023; 1(1), 30–36.

7. EI Obeagu & Tukur M. School-based initiatives: fostering sickle cell disease education. Elite Journal of Health Science, 2024; 2(5), 12–18.