Beta-thalassemia Major Patients Research Articles

Correlation of iron metabolism genes haplotypes with beta thalassemia major patients in Palestine

Correlation of iron metabolism genes haplotypes with beta thalassemia major patients in Palestine

A Study of Hepcidin Gene Polymorphism in Beta Thalassemia Major Egyptian Patients Refractory to Iron Chelation

A Study of Hepcidin Gene Polymorphism in Beta Thalassemia Major Egyptian Patients Refractory to Iron Chelation

Acute Graft versus Host Disease in Beta Thalassemia Patients Following Allogeneic Haematopoietic Stem Cell Transplantation.

To analyse the frequency, risk factors, and clinical symptoms of acute graft-versus-host disease (aGvHD) in patients with beta-thalassemia major after allogeneic haematopoietic stem cell transplantation (HSCT). Descriptive study. Place and Duration of the Study: Department of Clinical Haematology, Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan, from January 2017 to December 2021. Data were obtained from patients diagnosed with bone and tissue malignancies (BTM) who had undergone haematopoietic stem cell transplantation (HSCT) and experienced aGVHD. Patients who experienced initial graft failure and individuals who underwent subsequent bone marrow transplantation were excluded. Total of 117 patients diagnosed with BTM underwent fully matched HSCT, including 76 (65%) males, and 41 (35%) females. The median age of the patients undergoing transplantation was 7.34±7.32 years and the donors' median age was 7.6±9.85 years. Among the donors, 53 (45.3%) were males and 64 (54.7%) were females. Gender disparity was observed in 46 (39.3%) instances as a female donor matched with a male recipient. A total of 106 individuals underwent bone marrow harvest (BMH); with 5 (4.3%) patients receiving peripheral blood stem cells (PBSC) and 6 (5.2%) patients receiving both BMH and PBSC. Acute GvHD was observed in 50 (42.7%) patients, including 30 (60%) males and 20 (40%) females. Grade I GvHD occurred in 32 (27.3%) individuals, Grade II GvHD in 16 (13.7%) patients, and Grade III GvHD in one (0.8%) patient. It had no statistically significant association with recipient/donor age, gender disparity, the source of the graft source, the dose of stem cells, or the presence of thymoglobulin (TG). Acute GvHD was observed in high frequency in Beta-thalassemia patients receiving morrow harvesting proportional to their gender distribution. Associated factors were GvHD prophylaxis measure, mucositis and, CMV reactivation. Beta thalassemia major patients, Acute graft versus host disease, Allogeneic haematopoietic stem cell.

Very low serum IGF-1 levels are associated with vertebral fractures in adult males with beta-thalassemia major.

Patients with beta-thalassemia major (BTM) often develop several endocrine disorders due to chronic iron overload. They are also prone to osteoporosis and vertebral fractures. Plasmatic insulin-like growth factor-1 (IGF-1) levels are often low in subjects with BTM, which origin is multifactorial. The aim of this study was to evaluate a possible relationship between serum IGF-1 levels and the presence of osteoporosis and/or vertebral fractures. We retrospectively evaluated the occurrence of vertebral fractures in 30 adult male patients affected by BTM (mean age 43.3 ± 7.9years) with low serum IGF-1 (median value 52.4ng/ml, 38.5-83.4). Only 6 of them (20.0%) were diagnosed with GH deficiency (GHD) after GHRH/arginine stimulation test, while 23 (76.7%) had osteoporosis and 12 (40.0%) had known vertebral fractures. All patients except one also showed at least one endocrine disorder. Serum IGF-1 was significantly lower in BTM patients with vertebral fractures compared to patients without vertebral fractures (U = 41.0, p = 0.005) while it was not significantly different between patients with low bone mass compared to patients without low bone mass. The diagnosis of GHD was significantly associated with lower serum IGF-1 (p = 0.001) and vertebral fractures (p = 0.002) but not with low bone mass. After ROC analysis, we found that very low IGF-1 (≤ 50.0ng/dl) was associated with vertebral fractures (sensitivity 83.3%, specificity 75.0%) and was also predictive of GHD (sensitivity 75.0%, specificity 100.0%). Our study shows that, in male patients with BTM, serum IGF-1 ≤ 50.0ng/dl is a marker of vertebral fractures and it is predictive of a diagnosis of GHD.

How Age, Sex and Transfusion Affects the Incidence of Endo-crine and Bone Density Disorders in Major Thalassemic Patients

Background: Beta-thalassemia major patients frequently have endocrinopathies. We tried to determine relation between demographic and transfusion factor and endocrinopathies.
 Methods: Major beta-thalassemia patients (n=114 cases), 3–38 yr of age, entered this study. Female to male ratio was 51/63. Children (less than 20 yr) formed 57% of participants. Information about bone mineral density (BMD) and hormonal and biochemistry blood evaluation including fasting blood sugar (FBS), ferritin, triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH), testosterone (males), and estradiol (females) entered data sheet.
 Results: Sex and ferritin level showed no significant correlation with above disorders. Age significantly correlated to short stature, diabetes, low BMD at femur and neck (P, 0.031, 0.008, 0.009 and <0.001, respectively). The risk of short stature had increased in 12 yr and older patients 7.71 times than younger patients (P= 0.008). The risk of diabetes had increased in 35 yr and older patients 26.25 times than younger patients (P= 0.03). The risk of Z-score ≤ -2 in femoral region has increased in 19 yr and older patients 5.84 times than younger patients (P= 0.002). The risk of Z-score ≤ -2 in spinal region has increased in 14 yr and older patients 17 times than younger patients (P= 0.007).
 Conclusion: The main factor related with endocrinopathies was age. The correlation between age and short stature, diabetes and low BMD was positive. Therefore, we recommend early monitoring of thalassemia patients (in their late childhood and early teenage) for these complications.

Correlation between hepatomegaly and transfusion frequency in thalassemia patients: A cross-sectional study.

Objective: To investigate the relationship between transfusion frequency, serum ferritin levels, and hepatomegaly in beta-thalassemia major patients. Study Design: Cross-sectional study. Setting: Thalassemia Center, Liaquat University Hospital, Hyderabad. Period: January 2023 to June 2023. Material & Methods: Among 158 patients, age until 19 years, and β-thalassemia type major was considered as inclusion criteria. Data regarding hematological parameters and hepatomegaly was collected after informed consent. Data was analyzed using SPSS (version 22). Chi-square test was used to investigate the association between ferritin levels and hepatomegaly while Pearson’s correlation was used assess the correlation between ferritin levels and transfusion frequency. P-Value ≤ 0.05 was considered as statistically significant. Results: Majority of the participants were males (58.22%) as compared to females (41.77%). The mean age of the study participants was 9.31±4.47 years, and the mean age at first transfusion was 8.98±0.93 years. Majority of the participants were underweight 107(67.72%). Monthly transfusion rate was 1.95±0.31.The mean serum ferritin levels among the study participants were 2033.06±1309.36 ng/mL. Hepatomegaly was found to be present in 99 (62.65%) of the study participants. Statistically significant positive correlation between the frequency of transfusion and serum ferritin levels (r = 0.71, p<0.05) was observed. The difference of hepatomegaly in low-ferritin vs high-ferritin was also found to be statistically significant (p<0.05). Conclusion: It was concluded that higher transfusion rates were associated with elevated ferritin levels, and there was a significant association between higher serum ferritin levels and the presence of hepatomegaly.

Does TNF-α 308G/A (rs1800629) gene polymorphism associate with liver and pancreas disorders in Iraqi adults with beta thalassemia major?

TNF-α has been considered as the key regulator of inflammatory responses and is known to be participated in the pathogenesis of several diseases. The aim of this study was to explore the relationship of (rs1800629) gene polymorphism associated to liver and pancreas disorders in sample of β-thalassemia major adult Iraqi Patients. Blood samples were obtained from 40patients suffered from beta thalassemia with pancreas disorder, along with 40patient suffered from thalassemia with liver disorder, and 40patient suffered from thalassemia without pancreas or liver, from Ibn Al-Baladi Hospital, Baghdad, and 40samples from age and gender-matched apparently healthy individuals as control group, all subjects with age more than 18years. TNF-308G/A (rs1800629) gene polymorphisms were assessed by Tetra- ARMS-PCR. The result of showed that heterogeneous GA and homogeneous AA genotypes were higher, while GG wild genotype was lower in beta thalassemia major patients with liver and pancreas disorders compared to control group. It can be concluded that the prevalence of TNF-α 308G/A SNP plus (A) allele could be associated with risk of liver and pancreas disorders in sample of beta thalassemia major adult.

A study conducted in a tertiary care hospital to assess the cardiac function in paediatric beta thalassemia major patients and correlation with serum ferritin levels which are indicative of chelation status of the patients

Background: Thalassemia is one of the common inherited blood disorders and Beta Thalassemia Major is a homozygous form of deficiency of beta globin chain synthesis causing severe transfusion-dependent anemia, manifesting between 6 and 24 months of life. Objectives: The objective of the study is to study the pattern of cardiac function in children and adolescents with beta-thalassemia major by 2D Echocardiography and its correlation with serum ferritin levels. Methods: Fifty subjects diagnosed with Beta Thalassemia Major, after applying the inclusion and exclusion criteria were included in Group 1, and 50 age and gender-matched subjects without Beta Thalassemia Major were included in Group 2. Serum ferritin level was measured using Cobas 6000 analyzer. Echocardiography was done with the following parameters: Posterior wall thickness-diastolic (PWT-D), posterior wall thickness- systolic (PWT-S), left ventricular internal diameter-diastole (LVID-D), left ventricular internal diameter-systole (LVID-S), septal thickness and tricuspid regurgitation (TR) velocity. Results: Among the 50 study population, 28 children belonged to the age group 5–10 years (56%) and 22 children belonged to the age group 10–15 years (44%). Among the cardiac parameters, The PWT-D, PWT-S, LVID-D, LVID-S, TR velocity, and septal thickness values were higher in the cases group compared to the control group with p values suggesting strong significance. The ejection fraction in the cases was lower than the control group with a strongly significant p-value. Conclusion: Children with thalassemia have impaired cardiac function and the degree of dysfunction is correlated to the serum ferritin levels. Regular transfusion and adequate chelation are essential to decrease morbidity and mortality.

Cognitive impairment in beta thalassemia major and intermedia pediatric patients: a cross-sectional study

BackgroundThalassemia is a commonly occurring genetic hemoglobinopathy worldwide. Periodic and routine blood transfusions, iron chelation therapy and splenectomy procedures are all required for the treatment of thalassemia. Numerous organs and bodily systems could be impacted by thalassemia, particularly the nervous system, which could impede cognitive performance. The study aimed to assess cognitive abilities of pediatric patients diagnosed with beta thalassemia major and intermedia.Patients and methodsA total of 168 participants [54 β-thalassemic major children, 51 with β-thalassemia intermedia and 63 age-matched healthy controls from both genders (85 girls and 83 boys)] with age ranging from 8 to 16 years were participated in a cross-sectional study. Cognitive function was evaluated for all children by using the Wechsler Intelligence Scale For Children 4th edition.ResultsCompared with control group, a significant decline was found in all Wechsler Intelligence Scale subtests as well as in verbal comprehension index, perceptual reasoning index, working memory index, processing speed index and full scale index scores of thalassemia major and intermedia patients (p < 0.001). When compared to children with thalassemia intermedia, the beta thalassemic major children showed a significant decrease in all Wechsler Scale subtests as well as in all its five index scores (p < 0.001).ConclusionsThe study concluded that thalassemia negatively affects and impairs cognition and intellectual capacities.

Incidence, management and outcome of Hepatic Veno-Occlusive disease /Sinusoidal Obstruction Syndrome after hematopoietic stem cell transplant in Thalassemia major patients: A prospective study of Pakistani BMT.

Hepatic Veno occlusive disease (VOD), also known as sinusoidal obstruction syndrome (VOD/SOS), is a post-transplant life threatening complication. In this study, we aimed to discuss the incidence, management and outcome of VOD in post allogenic transplant patients of beta thalassemia major (BTM). A prospective study was conducted in Armed Forces Bone Marrow Transplant Center, between 2001-2022. A total of 385 fully Human Leucocyte Antigen (HLA) matched BTM patients, with Ursodeoxycholic acid for prophylaxis, were included in the study. Incidence of VOD was calculated through cumulative incidence estimates. Chi square test and Mann Whitney test were used to compare discrete and continuous variables respectively. VOD was diagnosed and graded according to European Society for Blood and Marrow Transplantation EBMT Pediatric diagnostic criteria. Risk factors for VOD were grouped as recipient, transplant and donor related. Univariate analysis was performed by log-rank test. All patients who developed VOD were managed primarily with fluid restriction and strict input output monitoring. Statistical analyses were performed using SPSS v 25.0. Out of 385 transplant patients, forty developed VOD. Median time from date of transplant till onset of VOD was 14 days (range 6-30). Cumulative incidence of all grade VOD was 10.39% (95% CI, 7-14). Eleven out of 40 patients who developed VOD died. Cumulative incidence of Transplant related mortality (TRM) for patients with and VOD was 20.5% (95% CI, 16.6-25.1) vs 27.5% (95% CI, 16.1-42) (p value 0.318) respectively. Among risk factors, age of recipient and fibrosis (p value of 0.04 and 0.000 respectively) were found to be significantly associated with VOD. Careful selection of transplant candidates before transplant can help reduce the incidence of VOD.

Low Vitamin D Levels Are Associated with Increased Cardiac Iron Uptake in Beta-Thalassemia Major.

We evaluated the association of vitamin D and parathormone (PTH) levels with cardiac iron and function in beta-thalassemia major (β-TM) patients. Two-hundred and seventy-eight TM patients (39.04 ± 8.58 years, 56.8% females) underwent magnetic resonance imaging for the assessment of iron overload (T2* technique), biventricular function parameters (cine images), and replacement myocardial fibrosis (late gadolinium enhancement technique). Vitamin D levels were deficient (<20 ng/dL) in 107 (38.5%) patients, insufficient (20-30 ng/dL) in 96 (34.5%) patients, and sufficient (≥30 ng/dL) in 75 (27.0%) patients. Deficient vitamin D patients had a significantly higher frequency of myocardial iron overload (MIO; global heart T2* < 20 ms) than patients with sufficient and insufficient vitamin D levels and a significantly higher left ventricular end-diastolic volume index and mass index than patients with sufficient vitamin D levels. PTH was not associated with cardiac iron, function, or fibrosis. In the multivariate regression analysis, vitamin D, serum ferritin, and pancreatic iron levels were the strongest predictors of global heart T2* values. In receiver operating characteristic curve analysis, a vitamin D level ≤ 17.3 ng/dL predicted MIO with a sensitivity of 81.5% and a specificity of 75.3% (p < 0.0001). In TM, the periodic and regular assessment of vitamin D levels can be beneficial for the prevention of cardiac iron accumulation and subsequent overt dysfunction.

Can N-acetylcysteine reduce red blood cell transfusion burden in patients with transfusion-dependent β-thalassemia?

Patients with beta-thalassemia major require lifelong and frequent red blood cell transfusions for survival, impacting their quality of life and life expectancy. This treatment approach poses risks of organ damage, iron overload, and increased transfusion-transmitted diseases. N-acetylcysteine (NAC) has been studied for its potential antioxidant effects on hemoglobin stability, aiming to reduce the burden of red blood cell transfusions. To explore this possibility further, we conducted a quasi-experimental study involving 35 individuals with thalassemia major over six months All subjects were already receiving iron chelators and blood transfusions. They were given a daily oral dose of 10 mg/kg NAC for three months. After three months of treatment with NAC, the serum levels of ferritin and liver enzymes (SGOT and SGPT) did not show significant changes (p = 0.35, p = 0.352, and p = 0.686, respectively). However, the red blood cell transfusion burden was significantly reduced in all patients after NAC therapy (p = 0.029), with no corresponding decrease in serum hemoglobin levels (p = 0.931), indicating maintained hemoglobin concentration despite reduced transfusion volume. The study indicates that NAC can effectively decrease the burden of red blood cell transfusions without significant toxicity in these patients. This finding suggests the potential for NAC as a cost-effective and manageable treatment option for these patients. A larger clinical trial with more robust statistical methods could further confirm these results and pave the way for using NAC as a valuable therapeutic agent for managing beta-thalassemia major patients.

Left atrial stiffness evaluation in beta-thalassemia major patients

Abstract Introduction Diastolic dysfunction is the earliest cardiac abnormality in β-thalassemia major (β-TM) patients and HFpEF is the predominant cardiac phenotype in symptomatic β-TM patients. Left atrial stiffness index (LASI) has been proved to have prognostic value in HFpEF patients. Purpose In our study we aimed to evaluate LASI in β-TM patients and assess its relation with conventional indices of diastolic function. Methods Sixty β-TM patients and twenty-nine controls were included in this cross-sectional study. Left ventricular ejection fraction (LVEF), early mitral inflow velocity to basal septal early diastolic velocity ratio (E/e'), left atrial volume index (LAVI), tricuspid valve regurgitation velocity (TVR) and left atrial deformation at reservoir phase (LASr) were calculated. T2* was used for myocardial iron load estimation. LASI was calculated as the [E/e’]/[LASr] ratio. Patients with LVEF &amp;lt;50% were excluded. LAVI, E/e’ and TVR were used as criteria of diastolic dysfunction. Results LASI was greater in patients compared to controls (0.30 ± 0.22 vs 0.18 ± 0.06, p = 0.003). Patients with diastolic dysfunction (n = 16) had greater LASI than patients without (n = 20) (0.49 ± 0.35 vs 0.21 ± 0.05, p = 0.001) as well as lower LASr (34.0 ± 15.6% vs 42.1 ± 6.7%, p = 0.043). Patients with indeterminate diastolic status (n = 24) had LASI = 0.26 ± 0.08 and LASr = 45.5 ± 13.6%. No correlation was found between LASI and T2* (p = 0.221). Conclusions β-TM patients with echocardiographic evidence of diastolic dysfunction have increased LASI. Myocardial iron load did not correlate with left atrial stiffness. A significant portion of β-TM patients have indeterminate diastolic function based on conventional criteria and novel indices, such as LASI or LASr, could be useful for reclassification of these particular patients.

Novel biochemical markers for the prediction of renal injury in beta-thalassemia major pediatric patients

Beta-thalassemia major is a severe inherited disorder characterized by inadequate production of hemoglobin beta chains, ineffective erythropoiesis, chronic hemolysis and necessitates lifelong transfusions, which lead to iron overload. The disease manifests itself in early childhood and persists throughout an individual’s life with a high risk of developing renal impairment, which cannot be reliably determined using routine markers. The objective of this research was to apply biomarkers to the evaluation of renal injury in pediatric­ patients within the age range of 1–14 years diagnosed with beta-thalassemia major. In the case-control study, the blood samples obtained in the Genetic Hematology Center in Thi-Qar Iraq Province were used: 60 samples from healthy individuals and 60 samples from the patients with beta-thalassemia, subdivided into 1-7 and 8-14 years old groups. The levels of hemoglobin, ferritin, creatinine and potassium were estimated with standard tests, enzyme-linked immunoassay was used to determine the level of neutrophil gelatinase-associated lipocalin (NGAL) and beta-2-microglobulin (β2M) as novel markers of tubular and glomerular dysfunctions. The study revealed a statistically significant decrease in hemoglobin, serum potassium levels and an increase in ferritin, NGAL and β2M levels in the patients from both groups compared to controls and elevation of creatinine level in the 8–14-year-old group. It was concluded that NGAL and β2M levels may be considered indicators for the early diagnosis of renal injury in pediatric patients with beta-thalassemia, as these biomarkers exhibit elevated levels before an increase in creatinine is observed. Keywords: beta-2-microglobulin, beta-thalassemia major, creatinine, ferritin, neutrophil gelatinase-associated lipocalin, renal injury

Iron Overload In Beta Thalassemia Major And Intermedia Patients In West Bengal

Iron overload is a significant concern in beta-thalassemia major and intermedia patients. These conditions lead to reduced production of hemoglobin, necessitating frequent blood transfusions. As a result, excess iron accumulates in the body, primarily in vital organs like the heart and liver. This can cause serious complications, including heart failure and liver damage. To manage iron overload, patients often require chelation therapy, which involves the use of medications to remove excess iron from the body. Regular monitoring and treatment are essential to mitigate the long-term consequences of iron overload in these individuals. This is a study to create awareness about the consequences of iron overload in the patients of West Bengal.

Coagulation Abnormalities in Pediatric Patients with β-Thalassemia, An experience at a Tertiary Care Hospital

Life expectancy in thalassemia has markedly improved due to consistent blood transfer and amenability with iron chelation therapy, therefore this improvement is conditioned with various thromboembolic problems of this prolonged disorder including thromboembolic complaints. Objective: To determine coagulation abnormalities in beta (β) thalassemia major patients who have been multi transfused. Methods: This observational study was conducted at Department of Haematology &amp; Transfusion Medicine, Children hospital &amp; University of Child Health Sciences (CH&amp;UCHS), Lahore, from October 2022 to January 2023. The study included 60 β-thalassemic patient, age less than 16 years whose samples were compared with upper and lower normal value as regards to Prothrombin Time (PT), Active Partial Thromboplastin Time (APTT), Protein S, Protein C, liver enzymes (Alanine Transaminase (ALT), Aspartate Transaminase (AST), Gamma-Glutamyl Transferase (GGT). The data were analyzed using IBM SPSS version 23.0. Results: When values were compared, natural clotting inhibitors (Protein S, Protein C) were remarkably reduced in β-thalassemic paeds patients (p&lt;0.001).PT and APTT were prolonged in thalassemic children (p&gt;0.05 and p&lt;0.05 correspondingly). There was substantial increase in concentrations of ALT and AST in β-thalassemic patients (p &lt; 0.001 and p &lt; 0.001 respectively) due to iron over load by multiple transfusions. Conclusions: Marked changes in coagulation inhibition supporting thrombotic tendency was observed in thalassemic children. There were reduced levels of protein C and protein S, independent of slightly prolonged PT and APTT and elevated levels of ALT, AST with normal GGT in thalassemic children.

Left Ventricular Myocardial Dysfunction Evaluation in Thalassemia Patients Using Echocardiographic Radiomic Features and Machine Learning Algorithms

Heart failure caused by iron deposits in the myocardium is the primary cause of mortality in beta-thalassemia major patients. Cardiac magnetic resonance imaging (CMRI) T2* is the primary screening technique used to detect myocardial iron overload, but inherently bears some limitations. In this study, we aimed to differentiate beta-thalassemia major patients with myocardial iron overload from those without myocardial iron overload (detected by T2*CMRI) based on radiomic features extracted from echocardiography images and machine learning (ML) in patients with normal left ventricular ejection fraction (LVEF > 55%) in echocardiography. Out of 91 cases, 44 patients with thalassemia major with normal LVEF (> 55%) and T2* ≤ 20 ms and 47 people with LVEF > 55% and T2* > 20 ms as the control group were included in the study. Radiomic features were extracted for each end-systolic (ES) and end-diastolic (ED) image. Then, three feature selection (FS) methods and six different classifiers were used. The models were evaluated using various metrics, including the area under the ROC curve (AUC), accuracy (ACC), sensitivity (SEN), and specificity (SPE). Maximum relevance-minimum redundancy-eXtreme gradient boosting (MRMR-XGB) (AUC = 0.73, ACC = 0.73, SPE = 0.73, SEN = 0.73), ANOVA-MLP (AUC = 0.69, ACC = 0.69, SPE = 0.56, SEN = 0.83), and recursive feature elimination-K-nearest neighbors (RFE-KNN) (AUC = 0.65, ACC = 0.65, SPE = 0.64, SEN = 0.65) were the best models in ED, ES, and ED&ES datasets. Using radiomic features extracted from echocardiographic images and ML, it is feasible to predict cardiac problems caused by iron overload.

Prevalence and Management of Transfusional Iron Overload in Syrian Beta Thalassemia Major Patients Pre and during the Syrian Conflict.

The primary aim of this study was to evaluate the prevalence of iron overload and the real-world clinical effectiveness of the iron chelation therapies (ICTs) in Syrian patients with transfusion-dependent beta thalassemia major (BTM) prior to and during the ongoing Syrian conflict. This single-center, two-stage observational study was conducted at Homs National Thalassemia Center (HNTC) prior to (2009) and during (2019) the armed conflict. The prevalence and the severity of iron overload, as well as the effectiveness of four iron chelation regimens, were assessed using serum ferritin (SF) concentrations as a means of monitoring in two cohorts of BTM patients receiving deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), or a combination of DFO and DFP therapy in both years. Statistical analyses encompassed one-way ANOVA, Kruskal-Wallis, Mann-Whitney U, and chi-square (χ2) tests for the comparisons of the variables and the frequencies between the two cohorts and subgroups. We included all eligible BTM patients at HNTC in 2009 (n = 205) and 2019 (n = 172). Only 84 patients from the 2009 cohort were accessible in 2019. Our findings revealed that 98% and 89% of the patients had iron overload (SF ≥ 1500 ng/mL) and comparable elevated median SF concentrations (3868 and 3757 ng/mL) in 2009 and 2019, respectively (P = 0.275). Furthermore, patients on DFO demonstrated the poorest control of iron overload and the highest SF concentrations (4319 and 5586 ng/mL), whereas those on DFX achieved superior outcomes and the lowest SF concentrations (3355 and 2152 ng/mL) in both years. Twenty-six patients from the 2019 cohort received no ICT for six years (from 2012 to 2018) and experienced extremely severe iron overload with SF levels ranging between 4481 and 16,000 ng/mL. Our findings prove a high prevalence of iron overload and suboptimal chelation outcomes in Syrian BTM patients, both prior to and during the ongoing armed conflict, despite the provision of free ICTs at HNTC. Poor adherence and older age of patients may explain the unfavorable outcomes of DFO and (DFO+DFP) regimens, whereas younger age and higher socioeconomic status may have contributed to the lowest SF and superior outcomes in patients on DFX. This study also demonstrates the crucial role of the National Thalassemia Centers, namely HNTC, in providing health services to BTM patients in times of peace and conflict.

Spectrum Of HBB Gene Variants And Major Endocrine Complications In Thalassemia Patients Of Pakistan.

To determine the molecular characterisation of beta-thalassemia major patients, pattern of major endocrine complications and its association with haemoglobin subunit beta gene variants. The cross-sectional study was conducted from November 2021 to November 2022 after approval from the ethics review committee of Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan, and comprised of 88 patients with beta thalassemia major aged >8 years and having serum ferritin level >1000 μg/L. The subjects were analysed for haemoglobin subunit beta gene variants and major endocrine complications, like growth retardation, hypogonadism, hypothyroidism, hypoparathyroidism and diabetic abnormalities using an automatic chemistry analyser, fully automatic chemiluminescence immunoassay analyser, enzyme-linked immunosorbent assay and real-time polymerase chain reaction. Data was analysed using SPSS 25. Of the 88 subjects, 40(45.4%) were girls and 48(54.5%) were boys. The overall mean age was 12±2.81 years. Of the total, 55(62.5%) had growth retardation, 41(46.6%) were cases of hypogonadism, 16(18.1%) hypothyroidism, 5(5.7%) hypoparathyroidism, 3(3.4%) diabetes mellitus and 8 (9.1%) had impaired glucose tolerance. Also, 65 (73.9%) patients confronted at least one endocrine complication. Endocrine complications were strongly associated with serum ferritin levels (p=0.000). The most common haemoglobin subunit beta gene variant identified was IVSI-5 (G>C) in 36 (40.9%), and the least identified variant was cluster of differenctiation-CD26(G>A) 1(1.1%). The association between haemoglobin subunit beta gene variants with endocrine complications was statistically non-significant (p>0.05). IVSI-5 (G>C) was found to be the most frequent haemoglobin subunit beta gene variant among beta- thalassemia major patients.

Assessment of the ovarian reserve in patients with beta-thalassemia major: a prospective longitudinal study

Repeated blood transfusions in women with beta-thalassemia major (BTM) may lead to iron overload and increase oxidative stress, consequently resulting in ovarian damage. The aim was to evaluate alterations in ovarian reserve in transfusion-dependent BTM patients over a time period of one year and to compare levels of anti-Mullerian hormone (AMH) in women with BTM and their healthy peers. This longitudinal prospective study was conducted in women with transfusion-dependent BTM at a tertiary level hospital. The hospital database was interogated for women diagnosed with BTM between 1996 and 2021. AMH levels were assessed at baseline and one year later. Forty-one women with BTM were identified, of whom 25 (60.9%) had amenorrhea and 16 (39.1%) had normal cycles. The mean AMH level of all women was 2.7±1.8 ng/mL at baseline, significantly lower than the age-matched nomogram value of 4.0±0.4 ng/mL for a healthy population (p=0.001). The baseline AMH level of patients with amenorrhea were significantly lower than patients with normal menstrual cycles (2.1±1.8 vs. 3.6±1.5 ng/mL, p=0.009). After one-year follow-up, there was a trend towards a decrease in the AMH levels of patients with normal menstrual cycles. Serum AMH values are decreased in patients with transfusion-dependent BTM. BTM patients should be educated about the possible effects of repeated blood transfusions on fertility.