Hemoglobin最新文献

Iron dysregulation in β-thalassemia major arises from a cycle of ineffective erythropoiesis, chronic transfusions, and suppressed hepcidin activity, leading to progressive iron overload and multi-organ toxicity. Erythroferrone (ERFE) plays a key role in modulating hepcidin and is associated with iron overload in β-thalassemia. This study aimed to evaluate ERFE and hepcidin levels in patients with β-thalassemia major with high plasma ferritin, and to compare them with those of healthy controls, while controlling for age, gender, disease progression, transfusion effects, chelation therapy, and splenomegaly. In this cross-sectional study, 85 participants (45 patients with β-thalassemia and 40 healthy controls) were enrolled. Blood samples were collected from patients 2 weeks post-transfusion to minimize the impact of the transfusion on ERFE and hepcidin levels. ERFE and hepcidin levels were measured by immunoassay. ERFE levels were significantly higher in patients with β-thalassemia (90.00 ng/ml [75.25 - 103.50]) than in controls (19.30 ng/ml [13.85 - 30.22]), whereas hepcidin levels were lower in patients (22.80 ng/ml [17.40 - 33.17]) than in controls (49.55 ng/ml [30.42 - 74.12]). Ferritin was significantly elevated in patients at 2998.00 ng/ml (1998.50 - 4087.50), concurrent with increased serum iron at 234.00 μg/dl (182.00-264.00) and decreased iron-binding capacity. Notable correlations included an inverse relationship between ERFE and hepcidin (ρ = -0.408, p = 0.005) and a positive correlation between ERFE and ferritin (ρ = 0.320, p = 0.032). These findings reveal a significant association of elevated ferritin with iron overload in β-thalassemia major. Hepcidin suppression appears primarily disease-driven, and ERFE inversely correlates with hepcidin levels. Targeted interventions are necessary to address iron overload and dysregulated hepcidin in affected individuals.

β-Thalassemia is a prevalent inherited disorder of β-globin chains. The clustered regularly interspaced short palindromic repeats (CRISPR) genome editing system has emerged as a potential curative strategy. We conducted a bibliometric analysis to map global research trends in CRISPR-based thalassemia research. Original and review research articles were retrieved from the Scopus database using the search terms [TITLE-ABS-KEY ('βeta thalassemia' OR 'β thalassemia' OR thalassemia*) AND TITLE-ABS-KEY ('gene edit*' OR crispr* OR 'clustered regularly interspaced short palindromic repeats')] AND [LIMIT-TO (DOCTYPE, 're') OR LIMIT-TO (DOCTYPE, 'ar')] for analysis. Bibliometric mapping and network visualization were performed using VOSviewer to analyze publication trends, authorship networks, international collaborations, keyword clusters, and citation metrics. Major CRISPR-based therapeutic strategies for thalassemia were reviewed to place experimental and clinical developments within a translational framework. The analysis demonstrates a clear transition from foundational genomic studies to translational applications, with leading contributions from the United States and China. Two dominant therapeutic strategies have emerged: direct correction of the HBB gene in hematopoietic stem cells and fetal hemoglobin reactivation via BCL11A repression. The latter strategy culminated in regulatory approval of exagamglogene autotemcel (Casgevy). Advances in base editing, prime editing, and strategies to improve engraftment are expected to enhance the precision and long-term efficacy of next-generation approaches. Clustered regularly interspaced short palindromic repeats-based research on thalassemia continues to expand, supported by extensive international collaboration and growing clinical translation. Future large-scale implementation will require advances in bioprocess engineering, cost reduction for ex vivo manufacturing, and adaptable treatment models for diverse healthcare systems.

Beta-thalassemia, caused by mutations in the β-globin gene, is an important disease for both basic and translational research. This hemoglobinopathy is molecularly and clinically heterogeneous, and its high prevalence in certain geographic areas has been attributed to a combination of evolutionary, environmental, and sociocultural factors. This report provides an update on the genetic dissection of β-thalassemia in western Andalusia (southern Spain) using a population genetics approach. The results were consistent with previous reports and support the idea of a specific substrate for the disorder in southwestern Iberia, with variant IVS I-1 (G > A) being a hallmark of autochthonous people. A single case of the hemoglobin variant Hb City of Hope (CD 69), a rare mutation reported in fewer than fifty individuals worldwide, was detected. Clinical differences associated with the specific β-globin mutation were also explored, with significance observed only for MCV when comparing mean values of IVS II-745 vs. CD 39 and IVS II-745 vs. IVS I-1.

Matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT) is a viable curative option for children with transfusion-dependent thalassemia major lacking a matched sibling donor. This study aimed to evaluate outcomes of MUD-HSCT in pediatric patients (≤ 12 years) because data on such a cohort are sparse. A retrospective analysis was conducted on 25 patients with thalassemia (≤12 years) who underwent MUD-HSCT. Data on patient demographics, transplant characteristics, post-transplant complications, and survival outcomes were collected. Kaplan-Meier survival analysis was used to estimate overall survival (OS), thalassemia-free survival (TFS), graft-versus-host and relapse-free survival (GRFS), and graft-versus-host and thalassemia-free survival (GTFS). Cox regression analysis was performed to identify predictors of GRFS. Median age at transplantation was 9 years; 60.9% were male. Most patients (68%) were Nanfang Class III. Median ANC and platelet engraftment occurred at 16 and 15 days, respectively. Acute and chronic GVHD were observed in 52% and 16% of patients, respectively. CMV reactivation occurred in 24%. Estimated 5-year OS, TFS, GRFS, and GTFS were 95.8%, 92%, 75.8%, and 92%, respectively. Elevated ferritin levels > 2500 ng/mL were independently associated with inferior GRFS (HR: 0.040; p-value = 0.031). In conclusion, MUD-HSCT yields excellent outcomes for OS and TFS in pediatric patients with thalassemia aged ≤ 12 years. High pre-transplant ferritin adversely impacted GRFS, underscoring the importance of iron control. These findings support MUD-HSCT as a viable option with appropriate pre-transplant optimization and GVHD management.

Sickle cell disease is a structural hemoglobinopathy with high global prevalence, especially in Africa. Neurological complications affect a high percentage of patients. An observational, retrospective, multicenter study was conducted in Aragon (Spain) among patients ≥12 years of age with sickle cell disease followed up between 2021 and 2022. Sociodemographic, clinical, analytical and therapeutic variables were analyzed, along with alterations in cerebral blood flow velocity assessed by transcranial and carotid Doppler ultrasound, and findings from imaging and magnetic resonance. Forty patients were evaluated (aged 12-58 years; 52.5% male). Forty percent of patients had pathological findings on magnetic resonance imaging (7.5% infarction, 17.5% silent infarcts, 5% cerebral aneurysms, and 5% stenosis). Only 7.5% of patients presented alterations in flow velocity assessed by transcranial Doppler ultrasound, with imaging of the carotid and middle cerebral arteries. The most severe phenotypes of sickle cell disease were associated with a higher incidence of neurological complications. Deficiencies in natural anticoagulant proteins were observed. This study shows low Doppler ultrasound sensitivity in screening for neurological complications in patients with sickle cell disease. Although the sample size is limited, this analysis provides relevant information and generates new study hypotheses about the value of incorporating structural neuroimaging into long-term follow-up strategies and thrombophilia studies in selected patients. However, larger prospective studies are needed to refine screening algorithms and determine the prognostic implications of neurological lesions in sickle cell disease.

Pyruvate kinase (PK) activators enhance glycolytic flux, increasing ATP production and lowering red blood cell (RBC) 2,3-diphosphoglycerate (2,3-DPG), thereby improving oxygen affinity and potentially reducing hemoglobin S polymerization in sickle cell disease (SCD). Through these biochemical effects, PK activation may decrease hemolysis and improve anemia. This systematic review and meta-analysis evaluated the impact of PK activators on hematologic and hemolytic parameters in adults with SCD. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception through April 2025 for clinical trials evaluating PK activators in adults with SCD treated for ≥2 weeks. The primary outcome was mean change in hemoglobin (Hb). Secondary outcomes included changes in lactate dehydrogenase (LDH) and absolute reticulocyte count (ARC). Random-effects models were used for all pooled analyses. Five early-phase clinical trials (n = 115) were included, predominantly involving adults with HbSS, most receiving concomitant hydroxyurea. PK activator therapy significantly increased Hb (mean difference [MD] 1.23 g/dL; 95% CI 1.03-1.43), reduced LDH (MD -83.2 U/L; 95% CI -115.9 to -50.2), and decreased ARC (MD -62.8 × 10³/µL; 95% CI -92.1 to -33.5). Heterogeneity was low to moderate across outcomes, and sensitivity analyses confirmed the robustness of effect estimates. PK activators improve key hematologic and hemolytic markers in adults with SCD, supporting their mechanistic potential as disease-modifying agents. Larger, randomized Phase 3 trials are needed to determine effects on clinical endpoints such as vaso-occlusive crises, transfusion requirements, and long-term safety.

This study aimed to evaluate health-related quality of life (HRQoL) and its determinants in patients with transfusion-dependent thalassemia (TDT) to inform clinical decision-making and patient-centered outcomes. A cohort of 111 patients aged 2-17.9 years from Ganzhou, Jiangxi Province, was assessed using the Chinese versions of the Pediatric Quality of Life Inventory 4.0, with concurrent analysis of sociodemographic, clinical, and genetic parameters. Comparative analysis revealed that TDT patients who had undergone hematopoietic stem cell transplantation (HSCT) had statistically significant improvements in total HRQoL scores and across four specific subdomains-physical, emotional, social, and school functioning-compared with transfusion-dependent controls. Effect size analysis indicated the most pronounced intergroup differences in physical and school functioning, exceeding established minimal clinically important difference thresholds. After adjusting for age and ferritin levels via multivariable linear regression, ongoing transfusion dependence and the presence of complications were identified as independent predictors of reduced HRQoL scores. In conclusion, HSCT is associated with a significant improvement in quality of life for patients with TDT. These findings underscore the importance of standardizing transfusion protocols and proactively managing complications to optimize long-term outcomes in TDT care.

Thalassemia syndromes result from a significant reduction in the synthesis of globin chains (α, β, γ, δ). An imbalance between α- and non-α-globin chains underlies β-thalassemia. α-Globin tetramers accumulate and precipitate in erythroid precursors (ineffective erythropoiesis). Hemolysis also plays an important role, shortening the erythrocyte lifespan. α-Thalassemia syndromes are caused by approximately 200 deletions and point mutations, as well as rare large deletions. More than 350 mutations have been identified in β-thalassemia syndromes, the majority of which are point mutations, with rare large gene deletions. Molecular genetic diagnostic methods include the amplification refractory mutation system (ARMS), reverse dot blot (RDB) for known mutations, Gap-PCR, multiplex ligation-dependent probe amplification (MLPA) for unknown deletion mutations, and Sanger sequencing for point mutations. In recent years, next-generation sequencing (NGS) methods such as targeted panel tests allow rapid, high-throughput detection of genetic variants; whole exome sequencing (WES) and whole genome sequencing (WGS) are also used. We use a diagnostic algorithm in our center as follows: β sequencing, α MLPA, α sequencing, β MLPA. If a diagnosis cannot be made with these tests, we use an anemia panel containing 214 genes, WES, or WGS. In this study, we present difficult cases encountered at our center and discuss methods used for cases with genetic diagnostic challenges reported in the literature.

Vitamin B₁₂ deficiency is a frequent but underdiagnosed complication in patients with transfusion-dependent β-thalassemia. Folic acid supplementation, commonly prescribed in this population, may mask hematological signs and alter homocysteine metabolism, complicating diagnosis. We conducted a cross-sectional study of 80 patients with transfusion-dependent β-thalassemia receiving daily folic acid supplementation (1 mg). Fasting serum vitamin B₁₂ and plasma homocysteine levels were measured, and the correlation between B₁₂ status and homocysteine was analyzed. Nineteen patients (23.8%) had biochemical vitamin B₁₂ deficiency (<200 pg/mL). However, the mean homocysteine concentration did not differ significantly between B₁₂-deficient and non-deficient patients (7.5 ± 4.2 vs. 6.39 ± 3.73 µmol/L; p = 0.420). No significant correlation was found between serum B₁₂ and homocysteine levels (r = -0.128, p = 0.267). In patients with transfusion-dependent β-thalassemia receiving folic acid supplementation, homocysteine may not reliably reflect vitamin B₁₂ deficiency, and normal levels should not be used to exclude deficiency. Routine screening with more specific markers, such as methylmalonic acid, may be necessary to prevent undetected B₁₂ deficiency and its neurological complications.

Pain is the defining factor of sickle cell disease (SCD), an inherited blood disorder. A cross-sectional study on the prevalence of the neuropathic component of pain in the Indian tribal population was conducted from August 2024 to June 2025 in Mysuru and Chamarajanagar districts, Karnataka. Forty eight individuals (aged ≥10 years, mean age 26 years) with the HbSS genotype were assessed using the painDETECT questionnaire, translated and adapted for local use. 48% exhibited painDETECT scores suggestive of a neuropathic pain component. 29.2% had a definitive neuropathic component and 18.8% had a probable neuropathic component. 35.4% of patients reported a pain pattern consistent with neuropathic features (pain attacks with/without pain between them). Pain radiation, a feature of neuropathic pain, was reported by 70.8% of individuals. No significant associations were found between neuropathic pain scores and age or gender. Our study highlights the prevalence of the neuropathic component of pain in SCD in the Jenu Kuruba and Soligas tribal populations of India. Further research is necessary to identify a standardized pain evaluation tool for this population. Individualized culturally sensitive, neuropathic pain specific interventions could significantly improve pain control and the quality of life in this underserved population.