Journal of Blood Medicine最新文献

Background: Awareness of inborn error immunity, such as Wiskott-Aldrich syndrome (WAS), is still lacking in Vietnam. The shortage of clinical immunologists and transplantation teams lead to poor prognosis for patients.

Objective: Describe initial data about hematopoietic stem cell transplantation (HSCT) for WAS.

Methods: Retrospective analyzing 15 procedures on 13 patients at the Vietnam National Children's Hospital from 2020 to 2024.

Results: The median age at HSCT was 34 months (range: 17-86). Of the patients, 73.3% received myeloablative conditioning based on busulfan, while 26.7% underwent reduced-intensity conditioning. Donor sources included matched sibling donors (MSD, 20.0%), unrelated cord blood (UCB, 33.3%), phenotypically identical family donor (MFD, 6.7%), and mismatched related donors (MMRD, 40.0%). The median stem cell dose was 4.9 × 10^6/kg of the recipient's body weight (range: 0.33 to 10.4 × 10^6/kg). Neutrophil and platelet engraftment occurred at a median of 14 days (range: 10-19) and 48 days (range: 14-143), respectively. By day +30, 73.3% of patients achieved full donor chimerism. One patient experienced graft failure, and another faced graft rejection two months post-transplant, both of whom underwent a second transplant with different donors. The overall survival rate was 92.3% with a median follow-up of 23 months (range: 6-53), with one patient died from chronic graft-versus-host disease (cGVHD). All surviving patients achieved normalization of platelet counts.

Conclusion: HSCT offers significant benefits to WAS patients, achieving an excellent overall survival rate.

Introduction: Hypercoagulability is one of the most reported state among Pregnant women. During pregnancy, the concentrations of D-dimer increase in a trimester-dependent- manner. The presence of gestational diabetes (GD) and gestational hypertension (GH) lead to further elevation in D-dimer levels. Pregnant women are at an increased risk of developing Venous thromboembolism (VTE), which can be fatal for both the mother and fetus. Elevated D-dimer levels during pregnancy could result in misdiagnosing other thrombotic diseases, emphasizing the need for further confirmatory testing for VTE. It is crucial to observe the plasma D-dimer concentrations among pregnant women at maternity and children's hospitals as it plays a role in guiding the anticoagulant treatments and minimizing the incidence of VTE among pregnant women.

Aim: The main objective of the current study was to detect the changes in the plasma D-dimer concentrations in healthy and complicated pregnancies across different gestational trimesters among women at the Maternity and Children's Hospital, Bisha, Saudi Arabia.

Methods: A cross-sectional study was conducted from March 2022 to March 2023, involving the analysis of plasma samples collected from 230 pregnant and non-pregnant women. Three samples were collected from each subject in each trimester. D-dimer measurement was conducted using an ACL Elite Pro Automated analyzer.

Results: The findings of this study show that D-dimer levels increased progressively throughout the pregnancy trimesters across all study groups. The increase was more noticeable among women with gestational diabetes (278.39 ± 29.808 ng/mL) and gestational hypertension (320.63 ± 12.157 ng/mL), suggesting that these complications influence D-dimer levels more significantly than healthy and multiple pregnancies. Notably, a positive correlation was found between age and D-dimer levels across all groups (p < 0.05), with the highest mean levels in the 41-48 age group.

Conclusion: D-dimer levels rise progressively throughout pregnancy and are significantly elevated in women with gestational diabetes and hypertension. These findings underscore the importance of interpreting D-dimer values in the context of gestational age and pregnancy complications. Additionally, maternal age influences D-dimer concentrations, emphasizing the need to interpret results within the context of age-related physiological changes during pregnancy.

Purpose: To describe the demographic and clinical characteristics of patients with hemophilia A receiving different levels of treatment personalization (TP), and to assess the relationship between TP and sport active time (SAT).

Patients and methods: This post hoc analysis of the CHESS II study used data from physician-completed patient record forms and patient self-completion forms for adult males receiving prophylaxis for severe hemophilia A in Europe between November 2018 and October 2020. SAT was assessed using propensity score matching (PSM) across levels of TP, including pharmacokinetic (PK)-guided and non-PK-guided.

Results: Of 54 patients, 32 (59.3%) received TP. Of these, 22 (68.8%) and 10 (31.3%) received non-PK-guided and PK-guided treatment, respectively. Median age varied between the TP and no-TP groups (29.5 and 34.0 years, respectively). Median (IQR) annual bleeding incidence was higher with non-PK-guided vs PK-guided TP (4.0 [3.0-8.0] vs 3.5 [2.0-4.0]). Median (IQR) problem joints were similar with non-PK-guided and PK-guided TP (1.0 [0.0-1.0] and 1.0 [0.0-2.0]). Patients in the TP vs no-TP group had higher median (IQR) SAT per month (3.3 [1.8-6.2] vs 1.8 [0.7-5.0] hours). Median (IQR) SAT per month was higher with PK-guided vs non-PK-guided TP (4.0 [3.0-20.0] vs 3.0 [1.3-5.3] hours). After controlling for confounding in the PSM model, SAT remained higher with TP vs no-TP and with PK-guided vs non-PK-guided TP. In both PSM models, P values were <0.05 for the average treatment effect and <0.01 for the average treatment effect on the treated. Sensitivity analyses confirmed the robustness of the PSM.

Conclusion: Patients receiving TP vs no-TP had higher median SAT. Of those with TP, those receiving PK-guided vs non-PK-guided TP experienced lower bleeding rates and higher SAT. PK-guided TP may help patients to be more active, potentially gaining the clinical and psychosocial benefits of exercise.

Introduction: Postoperative bleeding is a significant complication in dental surgeries, especially for patients on anticoagulants. Risk stratification based on patient factors can help reduce these complications, but current tools lack accurate risk prediction.

Aim: To examine point-of-care device accuracy for measuring International Normalized Ratio (INR) compared to laboratory INR and evaluate risk factors for post-dental surgical bleeding in warfarin patients.

Methods: The primary outcome was post-operative bleeding following invasive dental procedures. INR measurements were performed using both point-of-care devices and laboratory methods. One-way ANOVA compared INR values across bleeding severity groups and procedure types. Independent samples t-test compared INR values between low (<5 mg) versus high (≥5 mg) warfarin doses. Levene's test assessed variance equality.

Results: The study included 88 patients (61.4% female, mean age 49.7 ± 14.1 years). Bleeding outcomes were: no bleeding (33.0%, n = 29), minimal bleeding (34.1%, n = 30), moderate bleeding (20.5%, n = 18), and severe bleeding (11.4%, n = 10). No significant differences existed between <5 mg versus ≥5 mg warfarin groups in point-of-care INR (2.51 vs 2.70, p = 0.235) or laboratory INR (2.54 vs 2.63, p = 0.572). Significant associations were found between physician and procedure type (p < 0.001) and between point-of-care and laboratory INR measurements (r = 0.717, p < 0.001). No correlation existed between INR level and bleeding.

Conclusion: Bleeding risk in warfarin patients undergoing dental procedures depends on procedure complexity and duration rather than INR level alone. Point-of-care INR devices demonstrated accuracy comparable to laboratory measurements, offering valuable risk assessment that may help predict bleeding risk and provide reassurance for low-risk cases.

Microangiopathic hemolytic anemia with associated multiorgan failure is a medical emergency. The differential diagnosis for microangiopathic hemolytic anemia is broad and requires a systematic, focused approach at ruling out serious causes. However, with the rise of new vaccines and sporadic reports of vaccine-induced microangiopathic hemolytic anemia, it is essential for providers to include vaccines as a potential cause on their differential diagnosis. Here, we report the first case of respiratory syncytial virus vaccine-induced microangiopathic hemolytic anemia, anuric renal failure, and metabolic encephalopathy in the world.

Background: Fetal hemoglobin (HbF) is found at a measurable amount in red blood cells (RBCs) called F cells. High fetal hemoglobin (HbF) levels are linked with milder forms of sickle cell disease (SCD). However, some patients with high HbF levels still have severe symptoms. This variability has been associated with HbF per F cell (HbF/F cell) concentration; thus, it is hypothesized that high HbF/F cell (≥10 pg) is crucial in determining SCD disease severity rather than the overall HbF and F cell levels. This study assessed the utility of these three HbF parameters as predictors of SCD clinical events in Tanzania.

Methods: A retrospective cohort study was conducted at Muhimbili University of Health and Allied Sciences, involving 92 SCD individuals aged ≥6 years, not on hydroxyurea, between September 2022 and February 2023. Data was collected from the Sickle Pan-African Research Consortium (SPARCO)-Tanzania registry. HbF/F cell was calculated as: HbF/F cell = (HbF% × MCH pg)/F cell%. STATA version 15 was used to analyze the association between HbF parameters and clinical events measured by ordinal logistic regression. A p-value <0.05 was considered statistically significant.

Results: Of the 92 SCD participants, the median age was 16 (IQR: 10-21) years, 53 (57.6%) were below 18 years, and males were 48 (52.2%). Eighty-two patients (89.1%) had HbF/F cells below 10pg. Males had significantly higher HbF/F cell levels with a median of 6.4 (IQR: 4.3-9.5) pg compared to females 5.3 (IQR: 3.5-6.5) pg (p-value = 0.004). Although, we did not observe a statistically significant association between HbF/F cell with clinical parameters, increased HbF and F cell percentages correlated with reduced odds of multiple blood transfusions by 11% (p-value = 0.016) and 3% (p-value = 0.020), respectively.

Conclusion: In this cohort, HbF and F cell levels remain important predictors of disease severity, as higher levels predicted reduced requirement for multiple blood transfusions in SCD patients, while HbF/F cells did not correlate with SCD clinical events.

Background: Higher-risk myelodysplastic syndromes (HR-MDS) are associated with increased progression to acute myeloid leukemia (AML) and poor prognosis.

Patients and methods: This chart review characterizes real-world treatment patterns, outcomes, and costs of HR-MDS in France, Germany, and the United Kingdom (UK). Treating oncologists collected data (01 January 2014-31 December 2016) for adult patients with HR-MDS (revised International Prognostic Scoring System [IPSS-R] score >3), who received first-line treatment (1LOT) and had ≥1 year follow-up post diagnosis or until death. Demographics, clinical characteristics, treatment patterns, outcomes, and healthcare resource use were collected during 1LOT. Kaplan-Meier methods were used for time-to-event outcomes. Costs, applied to resource use, were calculated through 1LOT.

Results: Forty-one physicians provided data for 95 patients (France, n=31; Germany, n=29; UK, n=35). At HR-MDS diagnosis, median patient age was 75 years, 62.1% were men, and 60.0% had very high-risk disease per the IPSS-R. Median follow-up was 34.5 months. In 1LOT, 89.5% of patients received azacitidine (median, 12.0 cycles). At the end of 1LOT, 24.2% of patients had a complete and 30.5% a partial remission. From start of 1LOT, median progression-free survival was 24.3 months. Overall survival (unadjusted) was 32.9 months in all patients and shorter in the 33.7% of patients with versus without AML transformation (17.0 vs 52.9 months). Costs for 1LOT were driven by adjunctive therapy and were higher for patients who were transfusion-dependent versus -independent at the start of therapy and who did versus did not have transformation to AML.

Conclusion: These results provide real-world data from France, Germany, and the UK on HR-MDS treatment patterns, clinical outcomes, and costs.

Background: Comparative studies on frontline haploidentical HSCT (haplo-HSCT) versus salvage haplo-HSCT after immunosuppressive therapy (IST) failure in severe aplastic anemia (SAA) are limited. To evaluate the effects of different transplantation timing on patient survival, the incidence of graft-versus-host disease (GVHD), and the risk of infection on the outcomes of patients with SAA.

Methods: This retrospective study included 82 SAA patients who underwent haplo-HSCT using the "Beijing protocol". Patients who underwent allogeneic HSCT within 3 months after diagnosis were in the first-line HSCT group, and patients who were treated with initial IST and followed with allogeneic HSCT after treatment failure or relapse were in the salvage HSCT group. Patients were categorized into the frontline HSCT group (n=40, 48.8%) and the salvage HSCT group (n=42, 51.2%) based on transplantation timing. All 82 patients received grafts from related haploidentical donors. Follow-up was until January 1, 2024, and all patients were followed for more than 12 months with a median follow-up of 49 (12-126) months, except for dead cases.

Results: Multivariate analysis identified salvage HSCT (HR: 5.344, 95% CI: 1.904-14.995), ferritin levels >1000 (HR: 5.588, 95% CI: 1.696-18.414), and CMV infection (HR: 11.909, 95% CI: 2.335-60.725) as independent risk factors for graft failure. The overall survival rate was significantly higher in the front HSCT group (90%, 36/40) compared to the salvage HSCT group (71.4%, 30/42) with mortality rates of 10.0% (4/40) and 28.6% (12/42), respectively (p=0.029). The expected 5-year OS was significantly higher in the frontline HSCT group compared to the salvage group. Salvage HSCT, ECOG score ≥1, and ferritin levels >1000 were identified as independent risk factors for prognosis.

Conclusion: Frontline haplo-HSCT demonstrates superior survival and safety compared to salvage haplo-HSCT in young SAA patients without a matched sibling donor, warranting further clinical adoption.

Purpose: Few patients scattered among centers complicate investigation of thrombotic thrombocytopenic purpura (TTP) and Evans syndrome (ES). Routinely collected Danish register data captures the total population and includes lifelong follow-up. We aimed to validate registered TTP and ES diagnoses and to explore clinical characteristics.

Patients and methods: We identified all patients in Denmark with diagnosis registrations indicative of TTP or ES in the Danish National Patient Registry 2000-2019, validated diagnoses through medical record review, and extracted and presented data on initial treatment and complications.

Results: Diagnoses for patients registered with TTP and ES were confirmed for 46% and 59%, respectively. Among validated TTP patients the most widespread complications at time of diagnosis were neurological symptoms or deficits, observed in 81% of cases. Other frequent types of complications in TTP patients were any organ failure (32%) and infection (25%). Initial management and complications did not change for patients diagnosed between 2000 and 2009 and 2010 and 2019, and survival remained constant (overall mortality 26%, median follow up of 8.4 years). Treatments and complications also remained unchanged for ES patients.

Conclusion: Overall, diagnostic accuracy, complications and prognosis have remained relatively constant for patients over the study period. These now validated cohorts of Danish TTP and ES patients will be utilized in future studies to examine long-term health outcomes.

Introduction: Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by damaged and dysregulated immune system due to breakdown in the selection process during clonal growth of immune cells. Studies have shown that patients with systemic lupus erythematosus (SLE) display altered gene expression patterns and increased double-stranded DNA breaks within their hematopoietic stem and progenitor cells (HSPC). However, the current animal models for SLE found in the existing literature predominantly emphasize the use of peripheral blood mononuclear cells (PBMC) over HSPC for the creation of humanized mouse models. Nevertheless, these prior models were constrained by the limited efficiency of human cell engraftment and limited PBMC ability to replicate the capacity of HSPC to generate human SLE cells that can engraft host mice, thus making the transplant protocol inadequate.

Patients and methods: Transplantation was initiated by extracting HSPC from stable SLE patients by leukapheresis. The collected cells were assessed for purity before storage at -80 °C. Humanized mice were conditioned with cyclophosphamide and total-body irradiation before receiving the HSPC transplant. After transplantation, the mice were administered human granulocyte-colony stimulating factor and sacrificed to evaluate autoantibodies and HSPC in their bone marrow and blood samples. Statistical analysis was performed using Student's t-test and one-way ANOVA.

Results: Upon human stem cells engravement into mice, we found a noteworthy presence of HSPC, as evidenced by the positive expression of hCD45, hCD34, and/or hCD44, and the production of human antinuclear antibodies. The results indicated that the transplanted mice generated reactive autoantibodies against human cells, similar to that observed in the human donor patient. These findings shed light on the survival and behavior of transplanted human stem cells in a mouse model.

Conclusion: In this study, we successfully induced immunodeficiency in mice for xenotransplantation with human peripheral stem cells.