Transfusion-dependent Β-thalassemia Research Articles

A systematic review of clinical trials for gene therapies for β-hemoglobinopathy around the world

Background aimsAmidst the success of cell therapy for the treatment of onco-hematological diseases, the first recently Food and Drug Administration–approved gene therapy product for patients with transfusion-dependent β-thalassemia (TDT) indicates the feasibility of gene therapy as curative for genetic hematologic disorders. This work analyzed the current-world scenario of clinical trials involving gene therapy for β-hemoglobinopathies. MethodsEighteen trials for patients with sickle cell disease (SCD) and 24 for patients with TDT were analyzed. ResultsMost are phase 1 and 2 trials, funded by the industry and are currently recruiting volunteers. Treatment strategies for both diseases are fetal hemoglobin induction (52.4%); addition of wild-type or therapeutic β-globin gene (38.1%) and correction of mutations (9,5%). Gene editing (52.4%) and gene addition (40.5%) are the two most used techniques. The United States and France are the countries with the greatest number of clinical trials centers for SCD, with 83.1% and 4.2%, respectively. The United States (41.1%), China (26%) and Italy (6.8%) lead TDT trials centers. ConclusionsGeographic trial concentration indicates the high costs of this technology, logistical issues and social challenges that need to be overcome for gene therapy to reach low- and middle-income countries where SCD and TDT are prevalent and where they most impact the patient's health.

P29 Evaluating the Appropriateness of the EQ-5D-5L Descriptive System and the Derived Health Utility Index Scores in Adults with Transfusion-Dependent Beta-Thalassemia: A Mixed-Methods Study

Transfusion-dependent β-thalassemia (TDT) is a severe form of β-thalassemia requiring lifelong red blood cell transfusions (RBCTs) and iron-chelation therapy. EQ-5D is commonly used to derive health utility index scores for use in cost-effectiveness analyses. However, despite the range of symptoms and functional impacts of TDT, prior studies show that EQ-5D health utility scores in TDT are often comparable to general population scores and may not adequately represent the impact of TDT. To our knowledge, this is the first study examining the appropriateness of EQ-5D-5L descriptive system (DS) for use in adults with TDT.

EE287 Healthcare Resource Utilization Among Patients with Transfusion-Dependent Beta-Thalassemia in England

Patients with transfusion-dependent β-thalassemia (TDT) have reduced or absent β-globin production and require regular red blood cell transfusions (RBCTs) for survival. This study aimed to describe the healthcare resource utilization (HCRU) associated with TDT in England.

EE58 Healthcare Resource Utilization Among Patients with Transfusion-Dependent Beta-Thalassemia in Italy

Patients with transfusion-dependent β-thalassemia (TDT) require regular red blood cell transfusions (RBCTs) for survival. This study sought to understand the healthcare resource utilization (HCRU) among patients with TDT in Italy.

PCR29 Sustained Humanistic Burden and Work Impact in Adults with Transfusion-Dependent Beta-Thalassemia (TDT): Results from a Global Longitudinal Survey

Transfusion-dependent β-thalassemia (TDT) is a severe form of β-thalassemia requiring frequent, lifelong red blood cell transfusions and iron chelation therapy. This longitudinal study examined the impact of TDT on participants’ health-related quality of life and work productivity.

PCR132 Symptoms and Impacts of Transfusion-Dependent Beta-Thalassemia: A Qualitative Interview Study and the Development of a Conceptual Model

Transfusion-dependent β-thalassemia (TDT) is a severe form of β-thalassemia that requires lifelong red blood cell transfusions (RBCTs) and iron chelation therapy beginning in infancy. To date, the impacts of TDT and current treatments on health-related quality of life (HRQoL) have not been qualitatively explored from a patient perspective.

Evidence that platelets from transfusion-dependent β-thalassemia patients induce T cell activation

A hypercoagulable state leading to increased risk for thrombotic events represents one of the most common complications observed in transfusion-dependent β-thalassemia (TDT) patients. TDT patients have increased frequencies of circulating activated platelets. However, there is no information so far if platelets from TDT patients can activate T cells. In the present study we showed that T cells treated with platelets from TDT patients showed significant increased surface expression of CD69 compared to the T cells treated with platelets from healthy individuals. Patients with splenectomy showed increased T cell activation compared to patients with intact spleen. No T cell activation was observed following incubation with plasma alone, nor with platelets from healthy subjects. The percentages of regulatory T cells (Tregs) were also examined. TDT patients showed statistically significant increased percentages of Tregs compared to healthy controls. Additionally, we observed a positive statistically significant correlation between the percentages of Tregs and the platelet-induced activated T cells in patients who were not treated with aspirin. TDT patients showed increased levels of sP-selectin, suPAR and GDF-15, molecules implicated in platelet activation. We show that platelets from TDT patients can activate T cells in vitro. This activation correlates with markers of platelet activation and increased numbers of Tregs, perhaps in an effort to eliminate immune dysregulation, conceivably secondary to platelet activation.

COMPARISON OF DEFERASIROX AND DESFERRIOXAMINE AS IRON CHELATORS IN MULTI-TRANSFUSED PATIENTS OF Β-THALASSEMIA MAJOR

This study aimed to compare the efficacy of deferasirox and deferoxamine in improving hematological and immunological parameters in patients with transfusion-dependent β-thalassemia major. 200 patients were enrolled in the study, with 100 receiving deferasirox and 100 receiving deferoxamine. The study was conducted at Mayo Hospital, Lahore. The patients were followed up for six months, during which various hematological and immunological parameters were measured at regular intervals. The data were analyzed using appropriate statistical methods. Both deferasirox and deferoxamine effectively improved hematological and immunological parameters in patients with β-thalassemia major. However, deferasirox was more effective than deferoxamine in improving hemoglobin, red blood cell count, and hematocrit levels. In contrast, there was no significant difference between the two iron chelators in their impact on white blood cell count and platelet count. Deferasirox appears to be a more effective iron chelator than deferoxamine in improving hematological parameters in patients with transfusion-dependent β-thalassemia major

Ferroportin inhibitor vamifeport ameliorates ineffective erythropoiesis in a mouse model of β-thalassemia with blood transfusions.

β-thalassemia is an inherited anemia characterized by ineffective erythropoiesis. Blood transfusions are required for survival in transfusion-dependent β-thalassemia and are also occasionally needed in patients with non-transfusion-dependent β-thalassemia. Patients with transfusion-dependent b-thalassemia often have elevated transferrin saturation (TSAT) and non-transferrin-bound iron (NTBI) levels, which can lead to organ iron overload, oxidative stress, and vascular damage. Vamifeport is an oral ferroportin inhibitor that was previously shown to ameliorate anemia, ineffective erythropoiesis, and dysregulated iron homeostasis in the Hbbth3/+ mouse model of β-thalassemia, under non-transfused conditions. Our study aimed to assess the effects of oral vamifeport on iron-related parameters (including plasma NTBI levels) and ineffective erythropoiesis following blood transfusions in Hbbth3/+ mice. A single dose of vamifeport prevented the transient transfusion-mediated NTBI increase in Hbbth3/+ mice. Compared with vehicle treatment, vamifeport significantly increased hemoglobin levels and red blood cell counts in transfused mice. Vamifeport treatment also significantly improved ineffective erythropoiesis in the spleens of Hbbth3/+ mice, with additive effects observed when treatment was combined with repeated transfusions. Vamifeport corrected leukocyte counts and significantly improved iron-related parameters (serum transferrin, TSAT and erythropoietin levels) versus vehicle treatment in Hbbth3/+ mice, irrespective of transfusion status. In summary, vamifeport prevented transfusion-mediated NTBI formation in Hbbth3/+ mice. When given alone or combined with blood transfusions, vamifeport also ameliorated anemia, ineffective erythropoiesis, and dysregulated iron homeostasis. Administering vamifeport together with repeated blood transfusions additively ameliorated anemia and ineffective erythropoiesis in this mouse model, providing preclinical proof-of-concept for the efficacy of combining vamifeport with blood transfusions in β-thalassemia.

Detection of a Rare Mutation in the Initiation Codon of the β-Globin Gene (HBB:C.2T > C; P.Met1Thr)

β-thalassemia is one of the most common inherited autosomal disorders in the northern Iraqi Kurdistan region. This study reports a rare mutation in the initiation codon of the β-globin gene (HBB: c.2T > C; p.Met1Thr) in an 11-year-old male with severe transfusion-dependent β-thalassemia. Molecular testing to uncover the mutations of the β-globin gene in the proband and his parents was performed by amplification and reverse hybridization. Sanger sequencing was conducted for further identification. A severe β-globin gene mutation in codon 8/9 [+G] was initially identified in the proband and his mother’s DNA samples. However, the detection of only one β-globin gene mutation was not enough to elucidate the patient’s severe phenotype. Thus, a rare mutation in the initiation codon was identified later in the proband and his father by Sanger sequencing. In thalassemias, the presence of a rare mutation should be suspected when the patient’s genotype does not correlate with the phenotype.

Red Blood Cell Alloimmunization and Autoimmunization in Blood Transfusion-Dependent Sickle Cell Disease and β-Thalassemia Patients in Al-Ahsa Region, Saudi Arabia.

The risk of developing transfusion-related complications, especially alloimmunization, is an ongoing concern for transfusion-dependent patients. It is important to determine the rate of alloimmunization and autoimmunization in Al-Ahsa Region, Saudi Arabia, where sickle cell disease (SCD) and thalassemia incidence rates are the highest in Saudi Arabia. A cross-sectional study was conducted to review the transfusion history of patients with SCD and thalassemia at the King Fahad Hospital (KFH) in Al-Ahsa, Saudi Arabia. 364 transfusion-dependent patients were included in this study. Alloimmunization rates in patients with SCD and thalassemia were 16.7% and 11.97%, respectively, while autoimmunization rates in patients with SCD and thalassemia were 5.3% and 0.7%, respectively. The most frequent alloantibodies among the study participants were against Kell, Rh blood group systems. Blood transfusion-related alloimmunization and autoimmunization compromise the proper management of chronically transfused patients. Ideally, extended matched phenotyping should be implemented to prevent alloimmunization and reduce the risk of developing blood transfusion-related alloantibodies.

Efficacy of Hydroxyurea in Transfusion-Dependent Major β-Thalassemia Patients: A Meta-Analysis.

The present meta-analysis was conducted to determine the efficacy of hydroxyurea in patients with transfusion dependent major β-thalassemia.The present meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analyses of Observational Studies in Epidemiology (MOOSE) guidelines.A systematic search was carried out to evaluate the efficacy of hydroxyurea in patients with transfusion-dependent B-thalassaemia using electronic databases, including MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE. The keywords used to search for relevant studies included "hydroxyurea", "thalassemia", "transfusion-dependent", and "efficacy".Outcomes assessed in the present meta-analysis included transfusion in one year and intervals between transfusions (in days). Other outcomes assessed in the present meta-analysis were fetal hemoglobin (%), hemoglobin (%), and ferritin levels (ng/dl). Total of five studies were included in the analysis enrolling 294 patients with major B-thalassemia.The pooled analysis reported that the mean interval between transfusions was significantly higher in patients receiving hydroxyurea compared to those not receiving hydroxyurea (mean deviation {MD}: 10.07, 95% CI: 2.16, 17.99).Hemoglobin was significantly higher in patients receiving hydroxyurea compared to its counterparts (MD: 1.71, 95% CI: 0.84, 2.57).Patients receiving hydroxyurea had significantly lower ferritin levels compared to those not receiving hydroxyurea (MD: -299.65, 95% CI: -518.35, -80.96).These findings suggest that hydroxyurea may be a promising and cost-effective alternative to blood transfusions and iron chelation therapies for beta-thalassemia patients. However, the authors noted that further randomized controlled trials are needed to validate these findings and to determine the optimal dosages and treatment regimens for hydroxyurea in this patient population.

Evaluation of conventional renal function tests in β-thalassemia major patients in Nineveh province

β-thalassemia is an inherited anemia, caused by impaired β-globin chain synthesis. The disease leads to serious health problems unless treated by regular blood transfusion and iron chelating therapy. However, complications from continuous therapy may arise due to iron overload and toxicity of iron chelating therapy, it may affects many organs in the body including the renal system. The present study was directed to study the changes in conventional renal function tests that may occur in β-thalassemia patients. The present study consisted of two groups of β-thalassemia patients; group A, 40 transfusion dependent β-thalassemia patients receiving only regular blood transfusion, age ranged 1-4 years; Group B, 40 transfusion dependent β- thalassemia patients receiving regular blood transfusion and deferroxamine chelation therapy, age ranged 4-20 years old. In addition to a control group C, 40 subjects, age ranged 1-20 years. Blood samples were collected and serum was separated for measurement of creatinine, urea, and ferritin. Urine samples were also collected for measurement of microalbuminuria. There was a significant decrease in serum creatinine, and a significant increase in serum urea in group B when compared with their control (P≤0.01). In addition, there was a significant increase in serum ferritin in groups A and B when compared with their controls (P≤0.01). On the other hand, there were no significant changes in microalbuminuria between groups A and B when compared with their controls. The results of the present study showed no deterioration in renal functions in β-thalassemia patients in both groups A and B regarding serum creatinine and urea in addition to microalbuminuria, although, subclinical alteration in renal functions could be expected in those patients, so that measurement of other early markers of renal dysfunction is occasionally recommended.

Hematological and Biochemical Parameters of β-Thalassemia Major Patients in Bushehr City: A Comparative Analysis

Background and Aims: β-thalassemia is the most common genetic disorder worldwide. β-thalassemia major results in severe anemia and serious complications. So, this study aims to evaluate the hematological and biochemical markers in β-thalassemia major patients in Bushehr city.
 Materials and Methods: Our study included 94 transfusion-dependent β-thalassemia major were compared with 94 normal healthy subjects as controls. Hematological assessments included complete blood count indices. The biochemical evaluations included liver, kidney, and thyroid function tests, lipid profile, sodium, potassium, calcium, phosphorus, fasting blood sugar, and serum ferritin.
 Results: All hematological parameters in patients, such as hemoglobin (p < 0.01), hematocrit (p < 0.01), mean corpuscular volume (p < 0.05), and mean corpuscular hemoglobin (p <0.05), were significantly reduced compared to the control group except mean corpuscular hemoglobin concentration which was insignificant (p > 0.05). Higher levels of triglyceride, phosphorus, fasting blood sugar, aspartate aminotransferase, alanine transaminase, alkaline phosphatase, uric acid, total and direct bilirubin, and lower levels of cholesterol, high-density lipoprotein, and low-density lipoprotein were observed in patients in comparison to the control group (p < 0.05). Serum sodium, potassium, calcium, and albumin was not significantly different from the control group (p > 0.05). The prevalence of primary hypothyroidism (thyroid stimulating hormone > 4.5 mIU/l and T4 < 5.6 μg/dl) was reported at 5.31%.
 Conclusions: This study emphasized the necessity for regular follow-up and evaluation of β-thalassemia, which could be used to improve treatment protocols.

5612617 EFFICACY AND SAFETY OF A SINGLE DOSE OF EXAGAMGLOGENE AUTOTEMCEL FOR TRANSFUSION-DEPENDENT-THALASSEMIA AND SEVERE SICKLE CELL DISEASE

Background: Elevated fetal hemoglobin(HbF) is associated with improved outcomes in patients(pts) with transfusion-dependent β-thalassemia(TDT) and sickle cell disease(SCD). Exagamglogene autotemcel(exa-cel; formerly known as CTX001) is a cell therapy designed to reactivate HbF via non-viral, ex vivo CRISPR/Cas9 gene-editing at the erythroid enhancer region of BCL11A in autologous CD34+ hematopoietic stem and progenitor cells(HSPCs). Early data from the pivotal trials CLIMB THAL-111(NCT03655678) and CLIMB SCD-121(NCT03745287) showed that a single dose of exa-cel increased HbF and total Hb sufficiently to eliminate red blood cell(RBC) transfusions(TDT) and vaso-occlusive crises(VOCs; SCD). Aims: To report efficacy and safety data from the first 75 pts dosed with exa-cel in the ongoing CLIMB THAL-111 and CLIMB SCD-121 trials. Methods: Following pharmacokinetic-adjusted busulfan myeloablation and exa-cel infusion, pts(12-35y) are monitored for engraftment, total Hb, HbF, BCL11A edited alleles, transfusions, VOCs(SCD only), and adverse events(AEs). Data presented as mean(min-max) unless noted. Results: 44 pts with TDT(age 21.3 [12-35] y) and 31 pts with SCD(age 22.5 [12-34} y) had been infused with exa-cel at data cut(follow-up 12.3 [1.2-37.2] mo and 9.6 [2.0-32.3] mo, respectively). 26/44 pts with TDT(59.1%) had β0/β0 or a β0/β0-like genotype(β0/IVS-I-110, IVS-I-110/IVS-I-110). In the 2-yr period before screening, pts with TDT received 36.0(15.0-71.0) units RBC/yr and pts with SCD had 3.9(2.0-9.5) severe VOCs/yr. After exa-cel infusion, all pts engrafted neutrophils and platelets. Median time to neutrophil and platelet engraftment was 29 and 43 days in pts with TDT and 27 and 32 days in those with SCD, respectively. Overall, 42 of 44 pts with TDT stopped RBC transfusions(duration 0.8 to 36.2 mo); 2 pts had not yet stopped transfusions but had 75% and 89% reductions in transfusion volume. By Month 3, increases in HbF and mean total Hb levels(>9 g/dL) were achieved, with mean total Hb levels increasing to >11 g/dL thereafter and were maintained. All pts with SCD(n=31) no longer had severe VOCs after exa-cel infusion(duration 2.0 to 32.3 mo). The mean proportion of HbF was >20% by Month 3, increasing to ~40% at Month 4 and was stable thereafter, with mean total Hb levels >11 g/dL after Month 3. Pts with TDT and SCD with ≥1 yr follow-up had stable proportions of edited BCL11A alleles in bone marrow CD34+ HSPCs and peripheral blood mononuclear cells. Two pts with TDT had serious AEs(SAEs) considered related to exa-cel. The first pt was previously reported. The second pt had delayed neutrophil engraftment and thrombocytopenia, which were considered related to both exa-cel and busulfan. All SAEs resolved. No pts with SCD had SAEs considered related to exa-cel. There were no deaths, discontinuations, or malignancies. Conclusions: Exa-cel infusion led to elimination of transfusions in almost all patients with TDT and elimination of VOCs in all patients with SCD, with associated clinically meaningful increases in HbF and total Hb that were maintained over time. Proportions of CRISPR/Cas9-edited BCL11A alleles remained stable after more than 1 year, indicating that long-term HSCs were successfully edited. The safety profile was generally consistent with busulfan myeloablation and autologous transplant. These results indicate exa-cel has the potential to be the first CRISPR/Cas9-based therapy to provide a one-time functional cure for TDT and severe SCD. Reference 1. Frangoul et al, N Engl J Med 2021; 384:252-260.

5610224 THE USE OF LUSPATERCEPT IN PATIENTS WITH β -THALASSAEMIA AND MULTIPLE SYSTEMIC COMPLICATIONS INCREASES HEMOGLOBIN LEVEL, DECREASES TRANSFUSION BURDEN, AND IS UNAFFECTED BY COMPLICATIONS. SINGLE THALASSEMIA AND SICKLE CELL DEPARTEMENT’S EXPERIENCE.

Introduction: Luspatercept is a novel recombinant protein that improves erythroid maturation and has been shown to reduce the transfusion burden in transfusion dependent β -thalassemia patients. The aim of this study is to evaluate transfusion needs, biochemical markers, and biomarkers of tissue iron overload in transfusion-dependent patients with -thalassemia and comorbidities following Luspatercept administration. Methods: In a single department of thalassemia and sickle cell disease over a 9-month period, 17 patients (Women/Men: 9/8, mean age: 50.61 years)with transfusion-dependent β-thalassemia were evaluated 12 weeks before Luspatercept administration and 12 and 24 weeks after Luspatercept administration, respectively. (image1:genotypes and cormobidities)The authors evaluated hemoglobin levels, transfusion demands, transfusion intervals, and biochemical markers. In parallel, they evaluated clinical comorbidities, liver iron content (LIC), liver fibrosis by Fibroscan, and left ventricular ejection fraction. Other treatments were provided to patients according to standard clinical practice. SPSS was used to perform statistical analysis of the results. p0.05 indicates statistical significance. Results: In three patients, the dose was increased from 1 mg to 1.25 mg/kg after three cycles of luspatercept, while in one patient there was no response and treatment discontinued. Five of the seventeen patients terminated treatment due to fatigue (4/5) and lower extremity edema (1/5). A non-statistically significant improvement in liver fibrosis and LIC was reported 24 weeks following the onset of treatment, whereas the ejection fraction improved. At 12 weeks, there was a statistically significant increase in hemoglobin levels, a decrease in blood needs, and longer intervals between transfusions. Patients continue to demonstrate statistically significant improvement in terms of improved transfusion intervals and hemoglobin levels 24 weeks after initiating therapy. Except for the increase in uric acid and LDH, the remaining biomarkers continue to improve without a statistically significant effect at 24 weeks. Ferritin levels decreased over a period of 12 to 24 weeks. There was no statistical correlation among comorbidities (pulmonary hypertension, atrial fibrillation, hypogonadism, osteoporosis, albuminuria, thrombophilia, hepatitis C, extramedullary foci) and genotypes in luspatercept response (Detailed results in table 1). Conclusions: Treatment with Luspatercept in TD patients with beta-thalassemia major and severe comorbidities has a positive effect on therapeutic efficacy. Table - of the results displaying different parameters in 17 patients pre- and post- Luspatercept administration parameter baseline 12 wks 0 to 12 wks (p<0.05) 24 wks 0 to 24 wks(p<0.05) 12 to 24 wks(p<0.05) Hb (g/dl) 10.11 11.4 <0.001 10.50 0.150 <0.001 transfused blood volume 3227 2427 <0.001 2320 0.054 <0.001 transfusion interval 15.58 21.76 <0.001 22.53 <0.001 <0.001 LIC 6.31 5.51 0,089 Fibroscan 7.57 6.82 0.093 E.F 56.59 59.53 0.011 Ferritin 1704 1204 0.139 816 0.234 0.014 LDH 311 328 0.720 412 0.263 <0.001 Uric Acid 5.5 5.7 0.421 6.38 0.28 <0.001

5612535 THE IMPACT OF COVID19 PANDEMIC ON TRANSFUSION DEPENDENT -THALASSEMIA MANAGEMENT: EXPERIENCE OF A SINGLE PEDIATRIC TREATMENT CENTER

Background: Health care systems have been facing COVID19 pandemic around the world for almost two years. Transfusion dependent (TDT) β-thalassemia patients represent a vulnerable group,totally dependent upon hospital-based services. Aims: Aim of the present study was to evaluate the impact of COVID19 pandemic on management of TDT patients in a single pediatric treatment center in Northern Greece. Methods: Patient records were reviewed in order to assess changes in management before and during the 24-month pandemic in Greece (03/01/2018-29/02/2020 and 03/01/2020 -28/02/2022, respectively) in terms of transfusion volume and transfusion frequency, mean value of pretransfusional hemoglobin, as well as laboratory parameters reflecting iron overload (ferritin levels, liver and heart MRI). Results: The study included 28 patients, 19 male (67.8%) and 9 female (32.2%), with an age range of 8 to 21 years. Mean number of hospital visits for transfusion was 19.97 ± 3,52/ year prior to the pandemic and 22.38 ± 4.35/year during the pandemic (p: 0.003). Average transfusion volume was 176.18ml ± 38.32/kg/year και 178.67 ± 37.64ml/kg/year, respectively (p: 0.54). With regards to hemoglobin level, mean value was 9.56 ± 0.42g/dl prior to the pandemic and 9.45 ± 0.48gr/dl during the pandemic period. As to iron overload, mean ferritin level was 1362.05 ± 517.56 ng/mL prior to the pandemic and 1021.27 ± 508.92 ng/mL during the latter time period (p:0.016). Out of 28 enrolled patients, 26 underwent heart and liver MRI before pandemic and 23 during the pandemic period. Mean LIC values were 6.84 ± 7.37 mg/gdw and 6.43 ± 6.46 mg/gdw (p: 0.97) before and during the pandemic, respectively (p:0.97). Myocardial MRI values were within normal limits both before and during the pandemic. Summary-Conclusion: Covid19 pandemic did not seem to negatively affect the primary goal of transfusion therapy (pretransfusion Hb), even if an increased number of visits was required in order to transfuse the same blood volume - due to limited availability of blood units per visit. Of interest, pandemic conditions appeared to favor patient adherence to chelation therapy. Reference 1. Jean-Mignard E et al, Transfusion Clinique et Biologique 2022; 29: 70-74

Incidence, characteristics and laboratory parameters of epistaxis in children with β-Thalassemia major at a Tertiary Care Hospital of South Punjab, Pakistan.

Objective: To find out the incidence, characteristics and laboratory parameters of epistaxis in children with β-thalassemia major visiting a tertiary healthcare facility of South Punjab, Pakistan. Study Design: Retrospective study. Setting: Department of Hematological Disorder, Thalassemia and Bone Marrow Transplantation Centre, and Department of Biochemistry, Bahawal Victoria Hospital, Quaid e Azam Medical College, Bahawalpur, Pakistan. Period: January 2021 to November 2022. Material &amp; Methods: The hospital record of children of both genders aged from 2 to 18 years of age with blood transfusion dependent β-thalassemia was analyzed. Children reporting at least 1 episode of epistaxis in the preceding period were included in the final analysis to find out the incidence, characteristics and laboratory findings of children presenting with of epistaxis. Results: Out of 3772 children with β-thalassemia major, 85 reported at least 1 episode of epistaxis showing the incidence of epistaxis as 22.5/1,000 cases of β-thalassemia major. The mean age of the children at the time of enrollment and at the time of diagnosis of thalassemia was 9.93±3.48 years and 1.23±1.26 years respectively. The mean monthly frequency of blood transfusion was 1.71±0.75 blood transfusions per month. The mean monthly epistaxis frequency was reported to be 2.35±1.71 while 59 (69.4%) children had 2 or more than 2 monthly episodes of epistaxis. The mean serum ferritin level was noted to be 4058±2173 ng/ml. Ultrasonography findings revealed mean spleen size to be 9.25±5.80 cm. Conclusion: The incidence of epistaxis episodes among children with β-thalassemia was very high. Chronic iron-overload seemed to be common abnormality among children with β-thalassemia that should be addressed to potentially reduce the risk of epistaxis among these children.

Non-Vitamin K Antagonist Oral Anticoagulants in Patients with β-Thalassemia.

Background. Patients with β-thalassemia have a high incidence of atrial fibrillation (AF) and other supraventricular arrhythmias. The use of non-vitamin K antagonist oral anticoagulants (NOACs) for thromboembolic prophylaxis in patients with β-thalassemia has not been systematically evaluated. Methods. We enrolled patients with transfusion-dependent β-thalassemia, who were on treatment with NOACs for thromboembolic prophylaxis of supraventricular arrhythmias. Data on thromboembolic and bleeding events were collected. Results. Eighteen patients were enrolled. The patients had a history of AF (sixteen), typical atrial flutter (five), and atypical atrial flutter (four). The patients were treated with dabigatran (seven), apixaban (five), rivaroxaban (four) or edoxaban (two). The mean follow-up duration was 22 ± 15 months. No thromboembolic events were reported. No major bleedings were observed. Three patients had non-major bleeding events. Two patients reported dyspepsia during treatment with dabigatran and were shifted to a different NOAC. Conclusions. Our study suggests the efficacy and safety of NOACs in patients affected by transfusion-dependent β-thalassemia.

Polyneuropathy Associated with Age of Starting the Transfusion and Serum Ferritin Level in Iranian Patients with Thalassemia Major and Intermedia

Considering the importance of managing patients with β-thalassemia and the importance of early detection of disease complications, we examined the rate of sensorimotor neuropathy in patients with β-thalassemia and the risk factors related to it. This cross-sectional study included 44 blood transfusion-dependent β-thalassemia patients aged 5 years and older. Nerve conduction studies (NCSs) were performed via standard procedures for both motor and sensory nerves. Neuropathy was observed in 14 patients (31.8%). NCS results for sensorimotor nerves in patients were within normal range. In motor NCS results, increased ulnar nerve amplitude was observed in patients with increasing age, and peroneal nerve delay in patients with an increase in serum ferritin level (p < 0.05). In sensory NCS results, delayed ulnar and sural nerves latencies were found in patients with an increase in serum ferritin level (p < 0.05). We provide data that sensorimotor neuropathy exists in thalassemia patients. It seems that with the increase of serum ferritin level and the age of patients, neuropathy becomes more obvious, while other factors such as gender, body mass index, and the number of transfusions may not be associated with neuropathy.