Thalassemia Research Articles

β-Thalassemia minor is associated with high rates of worsening anemia in pregnancy.

We identified 347 pregnancies in patients with beta thalassemia minor. Hemoglobin was below 9 g/dL in 31% during third trimester and 7.6% at delivery. Postpartum hemorrhage occurred in 8.9%. Forty-six percent of intravenous iron administration was to iron-replete patients.

Outcomes of Hematopoietic Stem Cell Transplantation in Patients With Thalassemia Major: How Do Anti-HLA Antibodies Impact?: The Impact of Anti-HLA Antibodies on Transplantation Outcomes in Thalassemia Major.

To investigate the effects of anti-human Leucocyte Antigen (HLA) antibody positivity on early hematopoietic stem cell transplantation (HSCT) results in patients with thalassemia major (TM). One hundred and twenty-four HLA-matched HSCTs were performed in patients with TM between 2015 and 2022. Ninety-one patients were screened for anti-HLA antibodies by testing panel reactive antigens (PRA). Demographic and transplantation characteristics of patients were recorded. The presence of PRA was tested with the Antibody Testing Assay (Luminex LIFECODES HLA Antibody Identification System). The number of PRA-positive patients was 54. There was no relationship between acute graft versus host disease (GVHD), chronic GVHD, grade of GVHD, and viral reactivation of the patients. However, platelet engraftment took around 3 days longer in the PRA-positive group (p = 0.05). The median number of erythrocyte transfusions was significantly higher in PRA-positive patients in the post-transplant period (p = 0.003), as was the median number of platelet transfusions (p = 0.003). Treosulfan conditioning increased the stable mixed chimerism (MC) rate by 3.8-fold (p = 0.011). In contrast, reduced rates of MC were found in patients who received matched unrelated donor cells or peripherally derived stem cells (p = 0.011 and p = 0.039, respectively) in the posttransplantation period in TM patients. PRA-positivity did not affect MC (p = 0.478). However, 80% of patients who had primary graft failure (n = 5; p = 0.59) and 75% of patients who died (n = 4) were PRA positive (p = 0.64), but these results were statistically insignificant due to the low number of patients. Anti-HLA antibodies primarily delayed platelet engraftment in TM patients and increased the erythrocyte and thrombocyte transfusion requirements. Although PRA positivity was more common in patients with primary graft failure or who died, there was no statistically significant impact of PRA positivity on chimerism, acute or chronic GVHD, viral activation, or mortality rates.

Shear Wave Elastography in the Assessment of Liver Iron Overload in Children With Beta Thalassemia Major

Abstract Shear wave elastography (SWE) is an ultrasound method that effectively demonstrates liver fibrosis. This prospective study aimed to compare magnetic resonance imaging T2* and SWE results of the liver in children with thalassemia major (TM). Patients with TM who had regular follow-ups were included. SWE was performed first, followed by MRI T2*. In addition, a healthy control group of the same age group, known to have no liver disease, was recruited. For these participants, only SWE was performed, and their results were compared with the SWE parameters of the TM patients. The study included 38 patients and 25 individuals who made up the control group. The groups with mild, moderate, and severe iron overload according to MRI T2* were compared in terms of SWE with parameters, and no statistically significant difference was found. However, when comparing the SWE parameters between the control group and patients, the median, average, and standard values were found to be statistically significantly higher in the patient group (P < 0.001, P < 0.001, P = 0.026). When comparing MRI T2* results, the median, average, and standard values were found to be statistically significantly higher in the patients with normal and mild iron overload (P < 0.001, P < 0.001, P = 0.033). SWE is an effective, more accessible, and easy-to-apply method for demonstrating early changes in the liver in pediatric patients with TM. This study serves as a guide for more comprehensive studies that may investigate the effect of SWE in this patient group.

Demographics, clinical profiles and healthcare utilization of patients with beta thalassemia major: A single centered study

Thalassemia is an inherited autosomal recessive blood disorder that occurs due to abnormal form of hemoglobin in the blood. It is an autosomal recessive condition caused by decreased formation of alpha or beta chains of hemoglobin. Pakistan continues to suffer from a high thalassemia burden with statistics rising every year. With around 10 million carriers across the country, it is reported that each year, around 5000 children are diagnosed with thalassemia. The aim of this study is to bridge the gap between the problems faced by thalassemic patients in Pakistan and the facilities not available to them as compared to the developed countries. Method: A cross- sectional study was conducted with the duration of this study was 12 months. The data was collected from six tertiary care hospitals and eight Thalassemia centers, with the selection based on the accessibility of data. The inclusion criteria for the study was: a clinical diagnosis of Beta Thalassemia Major and age group between 1-18 years, irrespective of gender. The exclusion criteria included patients who were over 18 years of age and had comorbidities or complications other than Beta Thalassemia Major, as well as those who did not give consent. A questionnaire was circulated to record the data. It had two parts. The first part included demographics and the second part had close-ended questions related to the treatment of Thalassemia. Results: The total number of participants were 255 in which 122 (47.8%) were males and 133 (52.2%) were females. A positive correlation was observed between age and hospital visits, showing that an increase in age was associated with an increase in hospital visits among Beta Thalassemia patients (p value< 0.05) (CL:95%). Positive correlation was observed between the age of patients and the number of Liver Function tests. (p-value<0.05) (CL: 95%), viral profile done per year and age among B-thalassemia major patients. (p-value< 0.05) (CL:95%) and between age and cbc conducted per month (p-value < 0.05). Another positive correlation was observed between weight and frequency of blood transfusions in B-thalassemia major patients (p-value< 0.05) (CL:95%) and weight and liver function tests conducted per year among thalassemia patients. (p-value< 0.05) (CL:95%). Conclusion: This study aims to highlight the problems faced by thalassemia patients in Pakistan and the facilities not available to them compared to developed countries. A cross-sectional study was conducted for 12 months, collecting data from six tertiary care hospitals and eight Thalassemia centers. A questionnaire was used to record data on demographics and close-ended questions related to thalassemia treatment. Positive correlations were observed between age and hospital visits, liver function tests, viral profiles, and CBCs conducted. Weight was positively correlated with the frequency of blood transfusions and liver function tests conducted per year.

EVALUATION OF THE RELATIONSHIP BETWEEN IRON LOAD, AGE, AND CARDIAC FUNCTION IN CHILDREN AND YOUNG ADULTS WITH THALASSEMIA MAJOR: A PULSED-WAVE DOPPLER AND TISSUE DOPPLER IMAGING STUDY

Objective: To determine the structural and functional cardiac differences in children and young adults with thalassemia major (TM) compared to healthy subjects using pulsed-wave Doppler and tissue Doppler imaging methods and determine the relationship between iron overload and these differences. Materials and Methods: We analyzed the data of pediatric and young adult TM patients (n = 44) aged 4–22 years and an age- and gender-matched control group (n = 40) in our hospital data system between Oct.01.2023 and Oct.01.2024. Height, weight, body mass index (BMI), systolic–diastolic blood pressure measurements, complete blood count, ferritin, cardiac T2* magnetic resonance imaging (MRI) values, and echocardiography results were recorded. In addition to comparisons between the two groups, correlation analysis was performed between ferritin–cardiac T2* MRI results and echocardiographic parameters and age in TM patients. Results: Our study showed growth retardation (low height standard deviation score (SDS), low weight SDS and low BMI SDS), dilatation of the left cavities (high left ventricular internal diameter end diastole (LVIDd)), increased left ventricular muscle mass (high left ventricular mass index (LVMI)), cardiac distinctive diastolic (restrictive pattern: left ventricular (LV) peak early diastolic flow (E)/peak late diastolic flow (A) and E/early diastolic myocardial peak flow (E') high), and subclinical systolic (LV peak systolic flow low and LV Tei index high) dysfunction. In addition, iron load (ferritin and cardiac T2* MRI) was correlated with LVMI, and cardiac diastolic and systolic function indicators. As age increased, ferritin value did not change, but cardiac T2* MRI value decreased and diastolic–systolic parameters worsened. Conclusion: Periodic cardiac T2* MRI and Doppler echocardiography examinations of patients with TM may detect subclinical myocardial dysfunction at an early stage, thus providing a window of opportunity for intervention.

Coexistence of Vascular Ehlers-Danlos Syndrome and Sticky Platelet Syndrome: A Lethal Combination in A Young Patient with Thrombophilia and Haemorrhagic Diathesis.

The coexistence of hypercoagulability and bleeding diathesis in the same patient represents a potentially lethal combination due to its complex management. Vascular Ehlers-Danlos syndrome (vEDS) and sticky platelet syndrome (SPS) are classified as rare diseases due to their low prevalence. vEDS is associated with bleeding tendencies caused by vascular wall fragility, while SPS is characterized by atypical arterial and venous thrombosis. We report a 27-year-old woman, smoker and regular consumer of energy drinks, with a medical history of subclinical hypothyroidism, minor thalassemia, recurrent joint sprains, high myopia, and anterior mitral valve prolapse, who was diagnosed with both vEDS and SPS type I. The patient experienced a catastrophic progression over a short time period, marked by numerous thrombotic and bleeding episodes, ultimately leading to a fatal outcome. This report documents the first known case of concurrent vEDS and SPS, highlighting the complexity and challenges in the management of these two rare conditions together. The interplay between these syndromes necessitates careful clinical consideration and the development of tailored management strategies to mitigate associated risks. This underscores the crucial role of the internist in overseeing such cases. Further studies are needed to explore new therapeutic strategies aimed at improving survival rates and outcomes for patients with this unique combination of disorders. The coexistence of vascular Ehlers-Danlos syndrome (vEDS) and sticky platelet syndrome (SPS) creates a unique clinical scenario where the underlying connective tissue weakness and platelet hyperaggregability synergistically increase the risk of both thrombotic and haemorrhagic events, complicating management strategies.Internists must assume a pivotal role in the integrated management of patients with vEDS and SPS, facilitating a multidisciplinary strategy that not only addresses the dual risk of thromboembolic and haemorrhagic complications but also emphasizes the importance of personalized treatment algorithms and ongoing surveillance to optimize long-term outcomes.

Prevalence of beta thalassemia, heart failure and valvular abnormalities in children at tertiary care hospital

Objective: to evaluate, stratified by age and educational attainment, the distribution of pediatric beta-thalassemia, heart failure, and valve anomalies in order to find any appreciable variations in the prevalence rates. Methods: A study using a cross-sectional design was carried out on 115 youngsters. There were two age categories of participants: 43.5 percent were between the ages of 2 and 9 and 56.5% were those over 10. Children's educational status was divided into two categories: those who attend school (8.7%) and those who do not (91.3%). Medical records were used to gather information on the prevalence of valvular anomalies, heart failure, and beta-thalassemia. P-values and other statistical analyses were used to assess the significance of variations in prevalence rates among different age and educational groups. Result: 17.4% of participants in the research had beta-thalassemia; there were no significant variations in this condition between age groups (p=0.101) or educational attainment (p=0.820). Children who attended school had a higher prevalence of heart failure (69.6%) than children who did not attend school (34.4%), however this difference was not statistically significant (p=0.625). Children who did not attend school (38.2%) had considerably higher rates of valve anomalies than children who attended school (8.6%); a p-value of less than 0.001 indicated a highly significant difference. Conclusion: The study finds no significant changes in the prevalence of beta-thalassemia or heart failure across age and educational status, but it does show a substantial difference in the prevalence of valvular anomalies between children who attend school and those who do not. These results highlight how crucial it is to address socio-economic and educational gaps in order to improve health outcomes for communities that are already at risk.

Comparison of the effects of deferasirox film-coated tablets (Jadenu®) and deferasirox dispersible tablets (Exjade®) in patients with beta thalassemia major: a preliminary report of the effects on the satisfaction, convenience, cardiac/liver MRI T2*, serum ferritin level, and biochemical profiles.

Deferasirox (DFX) is a once-daily oral iron chelator with proven dose-dependent efficacy in patients with thalassemia major (TM). The reason for switching from DFX dispersible tablets (Exjade®) to DFX film-coated tablets (Jadenu®) was intolerance. Many patients also reported that deferasirox® did not taste good. In this study, we compared the effect of Jadenu® and Exjade® on satisfaction, convenience, cardiac/liver MRI T2*, serum ferritin levels, and biochemical profiles in patients with thalassemia major. Sixty-two patients with thalassemia over 2years of age, who had iron overload indicated by chelation therapy, were randomly divided into two groups. The first group (n = 32) is treated with Exjade®, and the second group (n = 30) is treated with Jadenu®. Laboratory investigations included alkaline phosphatase (ALK), alanine transferase (ALT), aspartate transferase (AST), and serum ferritin levels. Cardiac/liver MRI T2* levels and patient satisfaction and convenience, were assessed before and 1year after starting therapy. The study found that 53.3% of Jadenu® patients were satisfied with the taste of the medication compared to only 12.5% of Exjade® patients, which was statistically significant (p = 0.001). Additionally, 40% of Jadenu® patients were satisfied with the ease of taking the medication compared to 28.1% of Exjade® patients, and again, the difference was statistically significant (p = 0.047). A comparison of the cardiac MRI T2* levels between the two studied groups showed no significant difference (p = 0.851). Jadenu® offers patients an improved formulation that can be taken on an empty stomach, has a better taste, and presents fewer gastrointestinal tolerability concerns. Overall, patient satisfaction is higher with Jadenu®, which may improve adherence and reduce the frequency and severity of complications associated with iron overload. This, in turn, may help mitigate cardiovascular and hepatic complications from iron overload in the long term. https://irct.behdasht.gov.ir/search/result?query=IRCT20210830052346N1.

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.

Dengue fever with atypical manifestations in a child with beta thalassemia major post splenectomy

Dengue is one of the significant public health concerns in endemic countries. With plasma leakage as the primary pathophysiology in the process of severe dengue infection with hemoconcentration and thrombocytopenia being the significant laboratory diagnostic features in children, the presentation in children with underlying hemato-oncological conditions is atypical and often, anemia is found in these children, instead of hemoconcentration. We describe a young boy with beta thalassemia major who underwent splenectomy for hypersplenism 5-months ago with dengue illness, characterized by features mimicking a severe post splenectomy opportunistic infection with fever, loose stools and abdomen tenderness. Leucopenia, thrombocytopenia, minimal pleural effusion, ascites and gall bladder wall edema prompted us to think of dengue and was found to be positive. Child improved with appropriate supportive care measures. Pediatricians should be aware of the differences in the presentation of tropical infections in children with hemato-oncological disorders. Tropical infections should be kept in mind even in children with underlying hemato-oncological conditions, to ensure diagnosis and appropriate management.

Chelation: The Double-Edged Sword. A Case Report of Invasive, Disseminated Mucor Mycosis in a Beta Thalassemia Major During Transplant

Chelation: The Double-Edged Sword. A Case Report of Invasive, Disseminated Mucor Mycosis in a Beta Thalassemia Major During Transplant

Health Related Quality of Life in Transfusion Dependent Patients with Beta Thalassemia at a Resource Constrained Center

Background: Beta Thalassemia is a prevalent genetic disorder of hemoglobin affecting a significant portion of the global population with approximately 3% of people worldwide being carrier of the gene. About 5% of the population in Pakistan carry the genes for Beta Thalassemia, leading to approximately 5,000 new diagnoses each year. Majority of the patients are treated with regular red blood cell transfusions combined with iron chelation, few being able to afford definitive treatment in the form of allogeneic bone marrow transplant (BMT). Due to high disease burden and lack of adequate health care facilities the patients get inadequate blood transfusions and suboptimum iron chelation leading to numerous complications, early death and quality of life (QoL) problems. Objective: To evaluate health related quality of life in transfusion dependent beta Thalassemia patients registered at a single center Study Design: Cross sectional observational study Place and duration of the study: The study was conducted on patients treated at Pakistan Thalassemia Welfare Society (Pathwel) Center of Hematology and BMT Rawalpindi, Pakistan for at least one year between January 2006 to June 2024. Methodology: We evaluated 136 patients of transfusion dependent beta thalassemia with age range of 2-35 years and registered for more than 1 year at the center. Patients with age less than 2 years, those receiving hydroxyurea, undergoing BMT or registered for less than 1 year were excluded from the study. A face to face interview with structured questionnaire was used for data collection. Caregivers were interviewed for children of less than 10 years of age. Modified version of World Health Organization Quality of Life Brief Version (WHOQoL-BREF) questionnaire assessing 4 domains of QoL i.e. physical health, psychological health, social health and environment was used. IBM SPSS statistics version 23 was used for statistical analysis. Results: The estimation of health-related quality of life (HRQoL) in beta thalassemia patients provides important insights in the disease and its management. Majority of the responders were patients themselves 52.2% vs. caregivers 47.8%. All the 136 patients were transfusion dependent, 52.2% were female, 47.8% male, 84.6% were children and 15.4% adults. Mean age of the patients was 10.72 years (range 2-35, SD = 6.85).Out of 120 school-going age patients 68.3% were attending school, 22.5% had never been to any school, 9.1% left education at some point due to health related problems. Forty one percent of the patients had access to public transport for coming to thalassemia center for treatment while 39% faced difficulty reaching hospital and used private taxis. Only 58% patients underwent regular medical checkup from their GPs, 3.7% had irregular follow up visits. Socioeconomic status was; 39% upper middle class, 39.7% lower middle class and 21.3% poor. About half of the patient's socioeconomic status was affected by their disease, 46.3% did not had any effect while 3.7% were unaware of any effect. Forty five percent patients needed once a month red cell transfusion, 38.2% twice a month and 16.9% more than twice a month. According to 69.1% responders blood at the center was easily available while 28.7% had difficulty in getting blood for transfusion. Majority of them had either Rh negative blood groups or preformed antibodies. Mean pre-transfusion hemoglobin was 7.3 g/dl (SD=1.2).Hepatitis B Vaccination status revealed; 83.1% vaccinated, 8.1% not vaccinated while 8.8% were unaware of their vaccination status. Hepatitis C positivity was seen in 25% of the patients at some point of life while 2.2% were positive for hepatitis B. Eight out of the 23 patients with transfusion requirement more than twice a month had positivity for hepatitis C. Conclusion: This study underscored the considerable negative impact of thalassemia and its treatment on health-related quality of life (HRQoL), particularly due to comorbidities, availability of the blood, low income and lack of adequate knowledge about the disease. It suggests that adjusting current thalassemia management and care practices could be beneficial. Implementing psychosocial and counseling programs could help patients discuss and accept their condition, support a normal lifestyle, and strengthen connectivity among patients, schools, families, and healthcare providers leading to improved HRQoL and academic performance.

Genetic Modifiers of Hemoglobin Expression from a Clinical Perspective in Hemoglobinopathy Patients with Beta Thalassemia and Sickle Cell Disease.

Hemoglobinopathies, namely β-thalassemia and sickle cell disease (SCD), are hereditary diseases, characterized by molecular genetic aberrations in the beta chains of hemoglobin. These defects affect the normal production of hemoglobin with severe anemia due to less or no amount of beta globins in patients with β-thalassemia (quantitative disorder), while SCD is a serious disease in which a mutated form of hemoglobin distorts the red blood cells into a crescent shape at low oxygen levels (qualitative disorder). Despite the revolutionary progress in recent years with the approval of gene therapy and gene editing for specific patients, there is an unmet need for highlighting the mechanisms influencing hemoglobin production and for the development of novel drugs and targeted therapies. The identification of the transcription factors and other genetic modifiers of hemoglobin expression is of utmost importance for discovering novel therapeutic approaches for patients with hemoglobinopathies. The aim of this review is to describe these complex molecular mechanisms and pathways affecting hemoglobin expression and to highlight the relevant investigational approaches or pharmaceutical interventions focusing on restoring the hemoglobin normal function by linking the molecular background of the disease with the clinical perspective. All the associated drugs increasing the hemoglobin expression in patients with hemoglobinopathies, along with gene therapy and gene editing, are also discussed.

Outcome of Allogeneic Hematopoietic Stem Cell Transplant in Patients with Beta Thalassemia Major: Experience from Resource Constrained Centers

Outcome of Allogeneic Hematopoietic Stem Cell Transplant in Patients with Beta Thalassemia Major: Experience from Resource Constrained Centers

Beta thalassemia minor: a potential risk factor for osteopenia and osteoporosis

A 74-year-old male patient with beta thalassemia minor presented in 2022 for a follow-up of osteoporosis diagnosed prior to 2004. At the time of presentation, his medical history included: radiation exposure to his head and neck, goiter, prostate cancer status post resection in 2019 without a history of anti-androgen therapy, and atrial fibrillation, for which he had been prescribed apixaban since 2021. Treatment with risedronate occurred from approximately 2004 to about 2011, with improvement in bone density to osteopenia. He had also taken vitamin D and calcium supplementation and engaged in regular weight-bearing exercise. The patient had no other known risk factors for decreased bone mineral density preceding the onset of his osteoporosis, and a previous workup for secondary causes of his osteoporosis etiology proved negative. We propose that beta thalassemia minor is potentially a risk factor for osteopenia and osteoporosis, and that bisphosphonates can be considered for management when therapeutic intervention is indicated. Even in the absence of other known risk factors, clinicians should consider periodically screening beta thalassemia minor patients with DXA for evaluation of bone health.

Investigation of Depression, Anxiety, Sleep Quality, and Fatigue in Thalassemia Major Patients: A Study of the Correlation Between Sleep Quality and Laboratory Findings.

Thalassemia major (TM) experiences a high rate of psychiatric problems, with frequent occurrences of depression and anxiety as well as a high incidence of insomnia. In the present study, we aimed to investigate the severity of depression, anxiety, sleep disorders, sleep quality, and fatigue and explore the relationship between sleep quality and laboratory parameters. Twenty-eight patients and 37 healthy volunteers were included. Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Beck Depression Inventory, Beck Anxiety Inventory, and Fatigue Severity Scale were used. We found 46.43% of TM patients had depression, 78.5% had mild anxiety, and 3.57% had severe anxiety. ISI score (p = 0.027), ISI subthreshold insomnia percentage (p = 0.027), PSQI global score (p = 0.002), PSQI insomnia percentage (p = 0.025), PSQI subjective sleep quality (p = 0.008), PSQI sleep latency (p = 0.003), fatigue score (p = 0.026), and chronic fatigue (p = 0.037) percentage were significantly higher in the patients group than in the controls group. Ferritin was positively correlated with PSQI subjective sleep quality (r = 0.478, p = 0.010) and fatigue score (r = 0.427, p = 0.023). Heart involvement in magnetic resonance imaging was positively correlated with ISI score (r = 0.426, p = 0.024) and ISI classification (r = 0.455, p = 0.015). Depression and anxiety were significantly higher in TM patients compared to healthy controls. Chronic fatigue and insomnia were more common in TM patients, with subjective sleep quality being impaired and sleep latency prolonged. Furthermore, it was observed that individuals with higher ferritin levels had higher scores of subjective sleep quality and fatigue. Additionally, as cardiac involvement increased, severity of insomnia also increased.

The Relationship Between Ghrelin and Iron Metabolism In Beta Thalassemia Major Patients

IntroductionStudies in beta thalassemia major (β-TM) patients have shown that the responses of HIF2α, hepcidin and ferroportin molecules to high iron levels are impaired. In recent years, studies conducted in patients with iron deficiency anemia have investigated the relationship between ghrelin hormone and iron metabolism. In this study, we aimed to contribute to the etiopathogenesis of this disease by examining the changes in ghrelin hormone levels in patients with β-TM.Material and methodsFifty-two β-TM and 23 controls were included in our study. Blood counts, routine biochemical parameters, HIF2α, hepcidin and ghrelin levels were studied in blood samples taken from the volunteers.ResultsErythrocyte indexes, serum bilirubin, iron, unsaturated iron binding capacity, total iron binding capacity and ferritin levels showed significant differences between two groups (p<0.05) . There was no significant difference between two groups for serum HIF2α and hepcidin levels. When two groups were compared, ghrelin levels were found to be significantly higher in patients (p<0.05). When the correlation between parameters was examined in all subjects, a weak positive correlation was found between ghrelin and HIF2α (r=0.263) (p<0.05) and a significant positive correlation was found between ghrelin and ferritin (r=0.417) (p<0.05).ConclusionsOur study showed that there is a positive correlation between ghrelin and ferritin levels. Elevated ghrelin levels in patients with β-TM may have an important role in regulating impaired iron metabolism. Molecular level studies are needed to determine synthesis pathways.

Gene Therapy: A Revolutionary Step in Treating Thalassemia.

Beta thalassemia is an inherited blood disorder that results in inefficient erythropoiesis due to genetic mutation that leads to the reduction or absence of the hemoglobin beta-globulin protein. Approximately 8.5% of UAE residents suffer from β-thalassemia, a significant health and financial problem. The treatment options available for β-Thalassemia major are limited and associated with a wide range of complications. β-thalassemia gene therapy is emerging as a potential novel treatment option that eliminates the complications caused by the current long-term treatment modalities and the associated economic burden. This paper reviews the scientific literature related to emerging gene therapy for β-Thalassemia by analyzing all the articles published from January 2010 to December 2023 in the English language on Databases like PubMed, Scopus, ProQuest, and CINAHL. The use of gene therapy has demonstrated promising outcomes for a permanent cure of β-Thalassemia. To conclude, gene therapy is an innovative solution. It demonstrates a promising future, but does come with its own setbacks and is something that must be tackled in order to revolutionize it in the medical world. FDA-approved ZYNTEGLO is a potentially one-time curative treatment for β-Thalassemia. Although cutting-edge, its use is limited because of the high cost-a price of USD 2.8 million per patient.

Immunological Changes and Complement Proteins in Major Thalassemia Patients Proteins Post-Splenectomy

Background: Thalassemia is one of the most prevalent genetic disorders worldwide, with infections being a leading cause of mortality due to compromised immune function. Specific Background: Prior studies suggest that major thalassemia patients are highly susceptible to microbial infections, possibly due to altered immunological profiles, particularly immunoglobulin (IgG, IgM) and complement (C3, C4) levels. Knowledge Gap: However, the specific immunological changes pre- and post-splenectomy in these patients remain underexplored. Aims: This study aims to assess the levels of immunoglobulins (IgG and IgM) and complement proteins (C3 and C4) in major thalassemia patients both before and after splenectomy compared to healthy controls. Results: Our analysis of 50 thalassemia patients (34 males, 16 females) and 30 healthy individuals revealed that thalassemia patients exhibited significantly lower levels of C3 and C4 (88.52±24.49, 21.20±6.66) compared to healthy controls (123.50±19.04, 32.87±9.77). IgG and IgM were elevated in patients (1288.12±467.87, 153.46±51.29) compared to controls (1129.93±295.96, 148.67±50.17). Post-splenectomy, patients showed a significant decline in IgG (1001.56±154.14) and IgM (110.08±25.83) levels, along with further decreases in C3 (83.28±24.13) and C4 (17.48±4.86). Novelty: This study provides novel evidence of the immunological shifts in thalassemia patients post-splenectomy, demonstrating significant reductions in both immunoglobulins and complement proteins, thereby elevating the risk of infection. Implications: These findings highlight the spleen's crucial role in maintaining immune competence and suggest that splenectomy in thalassemia patients requires careful post-operative immune monitoring to mitigate infection risks. Highlights: Splenectomy lowers IgG, IgM, C3, and C4 levels in thalassemia patients. Post-splenectomy patients face higher infection risk due to immune weakening. Highlights spleen's crucial role in immune defense for thalassemia patients. Keywords: Thalassemia, Splenectomy, Immunoglobulins, Complement Proteins, Immune Competence

The Utility of Micro-R/Hypo-He Ratio Cut-off for Distinguishing Iron Deficiency Anemia and Minor Thalassemia

Thalassemia is a genetic disease with impaired synthesis of the globin chain that causes anemia. Thalassemia and Iron Deficiency Anemia (IDA) are both microcytic hypochromic anemia but have different proportions of hypochromic and microcytic erythrocytes due to differences in disease mechanisms. Research parameters of the hematology analyzer: %Micro-R, %Hypo-He, and MH ratio can be used as early screening for thalassemia and IDA. This study aimed to evaluate the cut-off of %Micro-R, %Hypo-He, and MH ratio to differentiate thalassemia from IDA. A cross-sectional study was carried out on 217 subjects. Subjects were divided into two groups, thalassemia and IDA based on hemoglobin electrophoresis, hematology examination, and Mentzer index. Differences and cut-off values of %Micro-R, %Hypo-He, and MH ratio between the two groups were analyzed. The number of collected data was 134, consisting of 89 thalassemia patients and 45 IDA patients. Thalassemia patients had a median %Micro-R value of 51.2 (4.3-79.0), %Hypo-He value of 7.2 (0.2-50.2), and MH ratio of 7.17 (1.10-64.50), higher than IDA patients (p=0.000; p=0.176; p=0.000). The optimal cut-off value for %Micro-R in discriminating thalassemia trait from IDA was >12.7, with the area under the ROC curve (AUC) of 0.945, sensitivity of 92.1%, and specificity of 82.2%. The cut-off value for MH ratio > 3.27 with AUC 0.833, sensitivity of 85.4%, and specificity 77.8% showed lower performance of cut-off value compared to %Micro-R. The algorithm using %Micro-R and MH ratio was proposed for thalassemia trait screening. High %Micro-R and MH are suggestive of thalassemia trait than of IDA.