Transfusion-dependent Thalassemia Research Articles

Quantitative MRI evaluation of iron deposition in patients with transfusion-dependent thalassemia: clinical management insights

ABSTRACT Background In patients with thalassemia, different organs are affected differently by iron overload. Nevertheless, the reasons for this could be the same key transporters. This study investigated the iron deposition in different organs of transfusion-dependent thalassemia (TDT) patients and its correlation. Research design and methods This cross-sectional study involved 54 TDT patients who underwent MRI T2* examinations of the heart, liver, pancreas, spleen, kidneys, and pituitary. The study analyzed the iron deposition in each organ and evaluated the correlation of iron deposition using Spearman’s test. Results Among the 54 patients with TDT, liver iron overload was found in 49/54 (90.7%) cases, pancreas iron overload in 43/54 (79.6%) cases, spleen iron overload in 18/26 (69.2%) patients, heart iron overload in 20/54 (37.0%) cases, and kidney iron overload in 8/54 (14.8%) patients. Most patients (66.7%) with iron overload in the liver but not in the heart exhibited spleen iron abnormalities. Pituitary T2* and pancreas T2* (r = 0.790), pituitary T2* and kidney T2* (r = 0.692), kidney T2* and pancreas T2* (r = 0.672) showed positive correlation (all p < 0.05). Conclusions Patients with TDT exhibited significant organ-specific iron overload. These findings highlight the importance of routine MRI screening for monitoring and managing iron overload in patients with TDT. Pituitary, pancreas, and kidney may have similar iron-loading mechanisms.

Contextualizing prophylactic red blood cell antigen matching in the lifelong care of sickle cell disease and thalassaemia patients.

Alloimmunization to minor red blood cell antigens has been linked to patient morbidity and mortality, especially among people living with sickle cell disease and transfusion-dependent thalassaemia. Prophylactic antigen matching is commonly used to prevent alloimmunization, but the evidence supporting this common practice is very limited. The report by Wolf etal. summarizes the latest literature on this topic and importantly finds that there is insufficient evidence to recommend prophylactic extended antigen matching (beyond ABO, RhD, RhCcEe and K). In an era of chronic blood shortages, this approach may help to assure patient access to elective surgery and cellular therapies, while preserving the supply of extensively antigen-matched red cells for patients with specific needs. Commentary on: Wolf etal. Red cell specifications for blood group matching in patients with haemoglobinopathies: An updated systematic review and clinical practice guideline from the International Collaboration for Transfusion Medicine Guidelines. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19837.

Role of Malondialdehyde Levels in The Occurrence of Hypogonadism in Transfusiondependent Thalassemia Male Patients

Role of Malondialdehyde Levels in The Occurrence of Hypogonadism in Transfusiondependent Thalassemia Male Patients

Beta Thalassemia in Children: Established Approaches, Old Issues, New Non-Curative Therapies, and Perspectives on Healing.

Despite a decrease in prevalence and incidence rates, beta thalassemia continues to represent a significant public health challenge worldwide. In high-resource settings, children with thalassemia have an open prognosis, with a high chance of reaching adulthood and old age with a good quality of life. This is achievable if transfusion therapy is properly managed, effectively mitigating ineffective erythropoiesis and its associated complications while also minimizing excessive iron accumulation. Adequate iron chelation is essential to maintain reactive forms of iron within the normal range throughout life, thus preventing organ damage caused by hemosiderosis, which inevitably results from a regular transfusion regimen. New therapies, both curative, such as gene therapy, and non-curative, such as modulators of erythropoiesis, are becoming available for patients with transfusion-dependent beta thalassemia. Two curative approaches based on gene therapy have been investigated in both adults and children with thalassemia. The first approach uses a lentivirus to correct the genetic defect, delivering a functional gene copy to the patient's cells. The second approach employs CRISPR/Cas9 gene editing to directly modify the defective gene at the molecular level. No non-curative therapies have received approval for pediatric use. Among adults, the only available drug is luspatercept, which is currently undergoing clinical trials in pediatric populations. However, in many countries around the world, the new therapeutic options remain a mirage, and even transfusion therapy itself is not guaranteed for most patients, while the choice of iron chelation therapy depends on drug availability and affordability.

Intravenous administration of iron dextran as a potential inducer for hemochromatosis: Development of an iron overload animal model

Iron overload in transfusion-dependent thalassemia patients represents a significant public health challenge due to its high mortality rate and risks of severe complications. Therefore, developing safe and effective therapeutic modalities for managing iron overload is critical, as current animal models inadequately replicate human conditions. The aim of this study was to investigate the effects of intravenous iron dextran on hepatocyte morphology, liver iron concentration, and serum iron profile changes as a model for hemochromatosis. An experimental design with a post-test-only control group method was conducted using animal models. Fifty rats were used and divided into ten groups, nine received different intravenous doses of iron dextran: 10, 20, 30, 40, 50, 60, 80, 100, and 120 mg/kg body weight (BW) and a control group received no treatment. The results showed that intravenous iron dextran starting at a dose of 10 mg/kg BW caused significant changes in liver iron concentration while starting at 20 mg/kg BW significantly affected hepatocyte morphology, transferrin levels, unsaturated iron binding capacity, serum iron levels, and transferrin saturation. Intravenous iron dextran starting at 40 mg/kg BW resulted significant changes in the level of total iron binding capacity compared to control group. In conclusion, intravenous iron dextran significantly altered hepatocyte morphology, increased liver iron concentration, and modified the serum iron profile, reflecting changes that might be observed in patients with transfusion-dependent thalassemia.

Bone turnover, areal BMD, and bone microarchitecture by second-generation high-resolution peripheral quantitative computed tomography in transfusion-dependent thalassemia.

Thalassemic osteopathy includes low bone mass and impaired bone microarchitecture. We aimed to evaluate the prevalence and determinants of bone quantity (osteoporosis) and quality (microarchitecture) in a cohort of adult patients with transfusion-dependent thalassemia (TDT). Patients with TDT (n = 63) and age- and BMI-matched controls (n = 63) were recruited in the study. Areal bone mineral density (BMD) was measured using DXA Hologic scanner. P1NP and β-CTX were estimated by electrochemiluminescence assay. Bone geometry and volumetric BMD (vBMD) were estimated by second-generation high-resolution peripheral quantitative computed tomography. Bone turnover marker β-CTX was significantly lower in the TDT group, but there was no difference in P1NP levels. Low bone mass (Z ≤ -2) was present in greater proportion of patients both at lumbar spine (LS) (54 vs 0%; p = .001) and femoral neck (FN) (33 vs 8%; p = .001). Hypogonadism was associated with low BMD at FN (OR 10.0; 95% CI, 1.2-86; p = .01) and low hemoglobin with low BMD at LS (OR 1.58; 95% CI, 0.96-2.60; p = .07). The mean trabecular bone score was also significantly lower in patients compared with controls (1.261 ± 0.072 vs 1.389 ± 0.058). Total, cortical and trabecular vBMD were significantly lower in cases than controls. The trabecular number and cortical thickness were significantly lower and trabecular separation higher in cases than controls. Adults with TDT have significantly lower areal, cortical and trabecular vBMD. The bone microarchitecture is also significantly impaired in terms of lower number and wider spacing of trabeculae as well as lower cortical thickness and area at both radius and tibia.

A rare mutation, deletion of HBB intron 2 to HBG1 exon 3 gene regions (12.6 kb) along with c.27dup, leading to transfusion-dependent thalassemia

A rare mutation, deletion of HBB intron 2 to HBG1 exon 3 gene regions (12.6 kb) along with c.27dup, leading to transfusion-dependent thalassemia

Role of Transient Elastography in Pediatric Transfusion Dependent Thalassemia Patients from Lower Socioeconomic Strata and its Correlation with Serum Ferritin: A Cross-Sectional Study

Role of Transient Elastography in Pediatric Transfusion Dependent Thalassemia Patients from Lower Socioeconomic Strata and its Correlation with Serum Ferritin: A Cross-Sectional Study

Exploring alterations of gut/blood microbes in addressing iron overload-induced gut dysbiosis and cognitive impairment in thalassemia patients

Iron overload causes cognitive impairment in thalassemia patients. The gut-brain axis plays an important role in cognitive function. However, the association between gut/blood microbiome, cognition, and iron burden in thalassemia patients has not been thoroughly investigated. We aimed to determine those associations in thalassemia patients with different blood-transfusion regimens. Sixty participants: healthy controls, transfusion-dependent thalassemia (TDT) patients, and non-transfusion-dependent (NTDT) patients, were recruited to evaluate iron overload, cognition, and gut/blood microbiome. TDT patients exhibited greater iron overload than NTDT patients. Most thalassemia patients developed gut dysbiosis, and approximately 25% of the patients developed minor cognitive impairment. Increased Fusobacteriota and Verrucomicrobiota with decreased Fibrobacterota were observed in both TDT and NTDT groups. TDT patients showed more abundant beneficial bacteria: Verrucomicrobia. Iron overload was correlated with cognitive impairment. Increased Butyricimonas and decreased Paraclostridium were associated with higher cognitive function. No trace of blood microbiota was observed. Differences in blood bacterial profiles of thalassemia patients and controls were insignificant. These findings suggest iron overload plays a role in the imbalance of gut microbiota and impaired cognitive function in thalassemia patients. Harnessing probiotic potential from those microbes could prevent the gut-brain disturbance in thalassemia patients.

Erythropoiesis and Gene Expression Analysis in Erythroid Progenitor Cells Derived from Patients with Hemoglobin H/Constant Spring Disease.

Hemoglobin H/Constant Spring (Hb H/CS) disease represents a form of non-deletional Hb H disease characterized by chronic hemolytic anemia that ranges from moderate to severe and may lead to transfusion-dependent thalassemia. To study the underlying mechanisms of this disease, we conducted an analysis of erythropoiesis and gene expression in erythroid progenitor cells derived from CD34+ hematopoietic stem/progenitor cells from patients with Hb H/CS disease and normal controls. Twelve patients with Hb H/CS disease and five normal controls were enrolled. Peripheral blood samples were collected to isolate CD34+ hematopoietic stem/progenitor cells for the analysis of cell proliferation and differentiation. Six samples from patients with Hb H/CS disease and three controls were subsequently studied for gene expression by next generation sequencing analysis. Erythroid progenitor cells derived from patients with Hb H/CS disease exhibited a trend towards increased rates of erythroid proliferation and decreased cell viability compared to those from controls. Moreover, erythroid progenitor cells derived from patients with Hb H/CS disease demonstrated delayed terminal differentiation. Gene expression profiling revealed elevated levels of genes encoding molecular chaperones, including the heat shock protein genes (HSPs) and the chaperonin containing TCP-1 subunit genes (CCTs) in the Hb H/CS disease group. In summary, erythroid progenitor cells derived from patients with Hb H/CS disease exhibit a trend towards heightened erythroid proliferation, diminished cell viability, and delayed terminal differentiation. Additionally, the increased expression of genes encoding molecular chaperones was observed, providing information on potential underlying pathophysiological mechanisms.

Magnetic Resonance Imaging T2* Study of Pancreatic and Tissue Iron Overload and Glucose Dysregulation in Young Children with Transfusion Dependent Thalassemia

Abstract Background MRI has become the gold standard for monitoring somatic iron stores. It is assumed that there would be a latency time before pancreatic iron burden could give impaired glucose tolerance. The therapeutic window between clinically silent iron deposition and irreversible pancreatic damage is an appropriate timing for intensification of iron chelation and saving organ function Objective The primary objective of our study is to determine pancreatic, cardiac and hepatic iron overload using MRI T2* in patients with transfusion dependent thalassemia(TDT) and correlate it with type and dose of iron chelation and serum ferritin. The secondary objective is to correlate these findings and the effect on Beta cell function and glucose dysregulation. Subjects and Methods This was a cross sectional study of 50 patients with TDT, 30 (60%) males and 20 (40%) females, aged 7-16 years. Clinical data involved mainly; frequency of transfusion, history of splenectomy, iron chelation therapy and compliance on medications in addition to anthropometric measures and Tanner staging. Laboratory work up included mainly mean pre-transfusion Hb, serum ferritin, serum fructosamine, fasting glucose and insulin levels with calculation of (HOMA-B and HOMA-IR) and MRI T2* to assess Cardiac, liver and pancreatic MRI. Results The mean age was 9.8 ± 2.52 yrs. Almost 40% of adolescents had delayed puberty (Tanner stage 1) of the studied TDT patients, 48% were on Deferasirox, 6% on Deferiprone, 20% was on Deferasirox &amp;Deferiprone and 18% were on Deferiprone &amp; Deferoxamine and two thirds were compliant on iron chelation therapy. Almost 50% were on hydroxyurea. The mean serum ferritin was 2646.6 ± 2334.55ng/ml. 16% had mild hepatic iron overload, 20% had moderate hepatic iron overload while 8% only had severe hepatic iron overload. Regarding the cardiac MRI results, 96% of studied group had no evident cardiac iron overload while 4% had moderate cardiac iron overload and 8% had evidence of severe pancreatic iron overload. The mean fructosamine was 236±56.72, mean HOMA-IR value was 1.4±0.79(0.32-2.5) yet only 4 patients(8%) had HOMA-IR of ≥ 2.5 indicating mild insulin resistance. There was significant positive correlation between LIC(p0.028), fasting glucose(p0.050), insulin level(p &amp;gt; 0.001) and HOMA IR, positive correlation between T2*-weighted MRI pancreas and insulin level (p0.026) as well as positive correlation between mean serum ferritin and insulin level(p0.001),negative non-significant correlation(p0.455) between mean serum ferritin and cardiacMRIT2*. Conclusion In patients with TDT, pancreatic siderosis (late onset presentation) was correlated with hepatic T2*;but not with the cardiac T2* values. Glucose homeostasis and markers of insulin resistance were correlated to pancreatic and liver iron load. Glucose dysregulation may precedes evident pancreatic siderosis so strict iron chelation is essential to maintain B-cell function.

Endocrinopathies in Adult Egyptian Thalassemia Patients, A Cross Section Study

Abstract background Endocrine abnormalities are the most common complications of transfusion dependent thalassemias (TDT). Although the prevalence of endocrinopathies is less in nontransfusion dependent thalassemias (NTDT), they are still encountered, especially with advancing age. This necessitates regular screening. Evaluation and treatment of endocrinological disorders are the same as that of transfusion dependent patients. Aim is to asses the common endocrinal disorders in patients with thalassemia; TDT and NTDT for early detection and replacement therapy. Subjects and Methods This study is across sectional study, it included 100 patients with thalassaemia; 50 patients who were (TDT) and 50 patients who were (NTDT). Patients who are ≥ 18 years old, with thalassemia major TM and thalassemia intermedia TI, Patients with or without splenectomy, Transfusion dependent and non-transfusion dependent patients, all were included in the study. Results Study showed that there is a statistically significant positive correlation between serum ferritin and thyroid stimulating hormone(TSH) and there is negative correlation with Sex Hormons, S.Cortisol, GH level. Also there is negative correlation between (Sex Hormons, S.Cortisol, Growth hormone GH) and frequency of transfusion. Study shows that Validity of serum ferritin at cutoff point more than 1100 for prediction of patients who are transfusion dependent.in terms of sensitivity was 100% and specificity was 90%. Conclusion thalassemia’s patients are still suffering from many endocrine disorders, and This necessitates early regular screening, as Early identification of endocrinal disorders and use of iron chelation reverse this disorders.

Combined effects of exercise and nutritional interventions on sarcopenia and its associated quality of life in transfusion-dependent thalassemia patients: a single-arm, open-label study

Combined effects of exercise and nutritional interventions on sarcopenia and its associated quality of life in transfusion-dependent thalassemia patients: a single-arm, open-label study

Vitamin D Deficiency among Blood Transfusion-Dependent Beta Thalassemia Children Admitted to Tertiary Level Pediatric Hospital in Nepal: A Descriptive Cross-Sectional Study

Introduction: Children with beta thalassemia are on regular blood transfusions, which could result in iron deposition in the liver causing decreased synthesis of Vitamin D-25OH. There are limited publications on the association of Vitamin D deficiency with blood transfusion-dependent thalassemia in the Nepalese population. This study aims to determine the prevalence of Vitamin D deficiency among blood transfusion-dependent beta-thalassemia patients.Methods: This was a descriptive cross-sectional study conducted among beta-thalassemia major patients under 15 years of age, receiving regular blood transfusion, from July 17, 2022, to July 16, 2023, after ethical approval obtained from Ethical Review Committee, Kanti Children’s Hospital (reference number 155). Data were collected using convenience sampling, and descriptive analyses were performed using Microsoft Excel and Statistical Package for Social Sciences (SPSS) 2024.Results: A total of 127 blood transfusion-dependent beta-thalassemia major patients were included in the study, of whom 82 (64.56%) were male. Among these patients, 104 (81.88%) were aged between 5 and 14 year. Almost one-third 41 (32.28%) had Vitamin D insufficiency, and a quarter, 34 (26.77%), had Vitamin D deficiency. Ten percent of the children were underweight, and a quarter were stunted.Conclusions: Children with blood transfusion dependent beta thalassemia major are at a greater risk for Vitamin D deficiency and iron overload

Outcomes of late endocrinologic evaluation in adult patients with thalassemia major: case series

AThalassemia is a group of inherited disorders characterized by the reduced or absent synthesis of the globin chains that make up hemoglobin. Transfusion-dependent thalassemia (TDT) is the most severe form, which requires lifelong transfusion. Complications related to the heart, liver and endocrine glands caused by the accumulation of excess iron in different organs due to transfusions are seen in adult patients. Of these complications, endocrine gland complications are widespread in adult patients. Hypogonadism is the most commonly reported endocrine complication, which affects 70-80% of thalassemia major patients. In this case series, we will present three female patients, aged 37, 18 and 27, who were followed up with the diagnosis of TDT and who underwent endocrinological evaluation in adulthood. We aim to emphasize that the diagnosis of hypogonadotropic hypogonadism and growth hormone (GH) deficiency was made late because the endocrinological evaluation of these patients was performed at an adult age, and we discussed the consequences of this. The survival of TDT patients has improved significantly in the last decade due to the introduction of transfusion, oral iron chelation therapies, and bone marrow transplantation, and these patients live into adulthood. Therefore, endocrinologic evaluation should be performed in pre-pubertal and pubertal periods. Early recognition of endocrine complications and early initiation of treatment are important to prevent irreversible sequelae.

Long term thalidomide therapy’s efficacy and safety in transfusion-dependent beta thalassemia major patients: a systematic review

Long term thalidomide therapy’s efficacy and safety in transfusion-dependent beta thalassemia major patients: a systematic review

Betibeglogene autotemcel (Zynteglo) for beta thalassemia.

Betibeglogene autotemcel (Zynteglo — Bluebird Bio), an autologous lentiviral vector cell-based gene therapy, has been approved by the FDA for one-time treatment of transfusion-dependent beta thalassemia in children and adults.

Assessment of growth retardation among transfusion-dependent Thalassemia patients in Peshawar, Pakistan

Assessment of growth retardation among transfusion-dependent Thalassemia patients in Peshawar, Pakistan

Blood Bonds: Transforming Blood Donation Through Innovation, Inclusion, and Engagement.

The journey of receiving blood as a patient with transfusion-dependent beta thalassemia has profoundly shaped my understanding of the life-saving power of blood donation. This personal experience underscores the critical importance of blood donors, not just for individual recipients but for the broader community, enhancing public health, productivity, and well-being. There are several challenges to securing a blood donor pool in current health care climate. Solutions that focus on the engagement of donors, clinicians, and patients are key to improving the donor pool and utilizing the blood supply in a judicious manner.

Prevalence of Hypothyroidism in Children with Transfusion Dependent Thalassemia Patient Attending in A Tertiary Care Hospital of Bangladesh

Background: Blood transfusions and iron chelation are standard treatments for β-thalassemia major and Hb E-Beta-Thalassemia. However, repeated transfusions raise body iron levels, leading to secondary hemosiderosis and complications in the heart, endocrine system, and liver. Thyroid dysfunction results from gland infiltration, chronic hypoxia, free radical damage, and iron overload. This study aimed to find out the prevalence of hypothyroidism in transfusion-dependent thalassemic children attending Bangladesh Shishu Hospital &amp; Institute. Methods: A descriptive cross-sectional study was conducted at the Thalassemia Centre, Department of Hematology and Oncology, Bangladesh Shishu Hospital &amp; Institute, from December 2019 to November 2020. The study included 140 children with thalassemia, aged 5 to 16 years, who were receiving blood transfusions. Data were collected using a structured questionnaire with participant consent. Statistical analysis was performed using SPSS version 23.0. Results: In this study, hypothyroidism was observed in 26.2% of patients, with 23.5% having subclinical and 2.9% overt hypothyroidism. In most of the patients (n=85), aged 11-16 years, 58.3% had normal thyroid function, 36.5% had subclinical, and 4.7% had overt hypothyroidism, which was statistically significant (p&lt;0.05). Of the 91 patients with hemoglobin levels below 11.5 g/dL, 85.7% had normal thyroid function, 13.2% had subclinical hypothyroidism, and 1.1% had overt hypothyroidism, also significant (p&lt;0.05). In the group with ferritin levels of 1200-2000 ng/mL, 78.1% had normal thyroid function, 18.8% had subclinical hypothyroidism, and 3.1% had overt hypothyroidism, which was not statistically significant (p&gt;0.05). Conclusion: Subclinical hypothyroidism is commonly seen in thalassemia patients aged 5 to 16 years who undergo regular blood transfusions. Regular physical exams and thyroid function assessments are crucial to detect overt hypothyroidism early. Timely hormone replacement can