Β-thalassemia Major Patients Research Articles

Frequency and potential risk factors of polyneuropathy in transfusion-dependent Β-thalassemia major patients: a cross-sectional study

BackgroundNeurological complications, including peripheral polyneuropathy, have been reported in β-thalassemia patients that negatively impact their quality of life. Chronic hypoxia, iron overload, average age, and iron chelators-induced neurotoxicity might contribute to the development of neuropathy. However, the leading offender of this complication remains not clear. We aimed to study the frequency and potential risk factors of polyneuropathy in β-thalassemia patients. We performed a cross-section study on 150 transfusion-dependent β-thalassemia major patients with a mean age of 16.44 ± 3.32 years. We performed electrophysiological studies for motor and sensory nerves.ResultsWe found that 31.3% of cases had neurological manifestations with significant relation to age, duration of the disease, and frequent transfusion. Out of 47 patients with neurological manifestations, 12 (25.5%) had abnormal nerve conduction velocity (NCV). Abnormal median, peroneal, and tibial nerve motor amplitudes were detected in 10.6%, 10.6%, and 14.9% of patients respectively. Abnormal median, peroneal, and sural nerve sensory amplitudes were detected in 4.3%, 2.2%, and 10.6% of patients respectively. Apart from a significant relation between abnormal NCV and older ages, no significant relation was detected with other studied clinical and laboratory parameters.ConclusionWe detected a high frequency of motor and sensory polyneuropathy in B-thalassemia patients. Polyneuropathy was predominately detected in older ages highlighting that neuropathy in thalassemia patients is probably age-dependent. Other factors including disease duration, transfusion frequency, and iron overload might have a contributing effect, however, that could not be confirmed in this study. Further studies are needed to verify the frequency and predictors of polyneuropathy in B-thalassemia patients.

Left atrial strain in patients with β-thalassemia major: a cross-sectional CMR study.

The aim of this cross-sectional study was to investigate the association of left atrial (LA) strain parameters with demographics, clinical data, cardiovascular magnetic resonance (CMR) findings, and cardiac complications (heart failure and arrhythmias) in a cohort of patients with β-thalassemia major (β-TM). We considered 264 β-TM patients (133 females, 36.79 ± 11.95 years) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia (E-MIOT) project. Moreover, we included 35 sex- and age-matched healthy controls (14 females, mean age 37.36 ± 17.52 years). Reservoir, conduit, and booster LA functions were analysed by CMR feature tracking using dedicated software. Compared to the healthy control group, β-TM patients demonstrated lower LA reservoir strain and booster strains, as well as LA reservoir and booster strain rates. However, no differences were found in LA conduit deformation parameters. In β-TM patients, ageing, sex, and left ventricle (LV) volume indexes were independent determinants of LA strain parameters. The number of segments with late gadolinium enhancement (LGE) significantly correlated with all LA strain parameters, with the exception of the LA conduit rate. Patients with cardiac complications exhibited significantly impaired strain parameters compared to patients without cardiac complications. In patients with β-TM, LA strain parameters were impaired compared to control subjects, and they exhibited a significant correlation with the number of LV segments with LGE. Furthermore, patients with cardiac complications had impaired left atrial strain parameters. Clinical relevance statement In patients with β-thalassemia major, left atrial strain parameters were impaired compared to control subjects and emerged as a sensitive marker of cardiac complications, stronger than cardiac iron levels. • Compared to healthy subjects, β-thalassemia major patients demonstrated significantly lower left atrial reservoir strain and booster strains, as well as left atrial reservoir and booster strain rates. • In β-thalassemia major, ageing, sex, and left ventricular volume indexes were independent determinants of left atrial strain parameters, while left atrial strain parameters were not correlated with myocardial iron overload. • An independent association between reduced left atrial strain parameters and a history of cardiac complications was found in β-thalassemia major patients.

Point Shear Wave Elastography Detected Liver Stiffness Increased in Pediatric Patient With Thalassemia Major.

Transient elastography (TE) and point shear wave elastography (pSWE) are 2 elastographic ultrasound examinations used in liver stiffness (LS) measurement. It was shown that the LS value detected by TE in pediatric β-thalassemia major patients has increased, and there was no LS evaluation obtained with pSWE in literature. Thus, in this study, it was aimed to evaluate LS with pSWE examination in children with thalassemia major and to determine LS-related parameters in these patients. Sixty-three schoolchildren with a diagnosis of β-thalassemia major and 21 healthy controls between the ages of 7 and 18 years were included. In addition to routine anamnesis, physical examination, and laboratory examinations, renal and liver ultrasounds were performed. Liver stiffness values were measured by pSWE examination. Serum levels of urea, aspartate-aminotransferase, alanine-aminotransferase, iron, and ferritin were significantly higher in patients, and serum creatinine, iron binding capacity, and hemoglobin levels were found to be significantly lower (P < 0.05 for each). Liver stiffness values were significantly higher in patients compared with healthy controls. In linear regression analysis, serum iron and iron binding capacity values were found to be closely related with LS (P < 0.001 vs. β = 0.482 and P = 0.047 vs. β = 0.237, respectively). Liver stiffness values obtained by pSWE examination increase significantly in patients. According to the results of our study, in addition to the previously known TE method, we think that the LS evaluation obtained by pSWE, a new method that can make more accurate measurements, can be used in the possible early detection of target organ damage in children with thalassemia major.

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.

Red blood cell alloimmunization in blood transfusion-dependent β thalassemia major patients in Sana’a City-Yemen

The development of erythrocyte alloantibodies complicates transfusion therapy in β thalassemia major patients. These antibodies increase the need for blood and intensify transfusion complications. Data on erythrocyte alloimmunization is scarce in Yemeni thalassemia patients. We studied the frequency of alloimmunization in multitransfused β-thalassemia major patients and investigated risk factors that affect antibody formation. Blood samples were taken from 100 β thalassemia major patients who received multitransfused leukodepleted packed red-blood cells. Antibody screening and identification were performed by indirect antiglobulin test using the gel column technique. All patients were tested for autoantibodies using autocontrol and direct antiglobulin test. No adsorption test was done as no autoantibodies were detected in any patient. In our study of 100 β-thalassemia patients, 50 were male and 50 were female with ages ranging from 1 to 30 years. Alloantibodies were present in 6% of patients, while no autoantibodies were detected. Of the 17 alloantibodies identified, the majority were directed against Kell (41.2%) and Rh (29.4%) blood groups. Alloimmunization was significantly associated with age group and sex (p = 0.013, p = 0.030), respectively in β thalassemia major patients. The development of alloantibodies was not significantly associated with duration, total number of transfusions and splenectomy (P = 0.445, P = 0.125, P = 0.647). No autoantibodies found in patients with β thalassemia major. The study found low rates of erythrocyte alloimmunization in multitransfused β-thalassemia major patients, but significant alloantibodies were produced primarily from Kell and Rh blood groups, suggesting the need for providing phenotypically matched cells for selective antigens to improve transfusion efficiency.

Diabetes mellitus progression in β-thalassaemia major patients: The impact of iron overload

ABSTRACT Regular blood transfusion therapy and enhanced iron absorption in patients with β-thalassemia major lead to progressive accumulation of iron in the patient’s tissues. Iron overload disrupts the function of pancreatic β-cell, deteriorates insulin resistance, increases blood glucose levels, and precipitates diabetes mellitus (DM). A family history of DM, obesity, sedentary lifestyle, and age increase the risk of DM in β-thalassemia patients. The prevalence of DM among individuals with β-thalassemia major is on the rise despite considerable screening and management efforts. Therefore, more research is still warranted to fully understand the molecular underpinnings linking β-thalassemia major and the onset and progression of DM to develop more robust screening and management approaches. In this context, no reliable biomarkers are currently available to predict or detect DM in such patients. In this review, we elaborate on key tentative links between thalassemia and DM and expand on established metabolic alterations that associate with DM in patients with β-thalassemia major. The review also addresses the prevalence rates and patient management strategies and underscores the need for identifying DM-related predictive and diagnostic biomarkers in β-thalassemia major patients.

Urinary biomarkers of early kidney injury in children with beta-thalassemia

Beta-thalassemia is considered as one of the most common genetic disorders in the world caused by the reduced or absent synthesis of b-globin chain. The aim of this work was to evaluate renal function in children with b-thalassemia using predictive biomarkers such as urinary neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl-b-D-glycosaminidase (NAG). This prospective case–control study was carried out on 80 subjects aged between 3 and 17 years. The subjects were divided into two equal groups: thalassemia group which included 40 children with b-thalassemia major, and control group which included 40 age- and gender-matched healthy, non-anemic controls without any diseases that could potentially affect renal function, who underwent routine check-ups. All thalassemia patients received chelation therapy: 35 (87.5%) of them were treated with deferasirox and 5 (12.5%) patients received deferasirox + deferoxamine. The results of echocardiography, kidney function tests (serum creatinine, urea and estimated glomerular filtration rate as well as urinary albumin/creatinine ratio and urinary NGAL/urinary albumin–creatinine ratio were insignificantly different between the two groups. Abdominal ultrasound findings were significantly different between both groups. Total WBC counts, platelet counts, the results of liver function tests (total bilirubin, direct bilirubin, alanine transaminase and aspartate aminotransferase), urinary NAG/creatinine ratios, urinary NGAL/creatinine ratios and serum ferritin levels were significantly higher in the thalassemia group, while hemoglobin, urinary NAG/urinary albumin–creatinine ratios were significantly lower in this group. Urinary markers NGAL and NAG could be used as predictive markers of renal disease in b-thalassemia major patients. The study was initiated after obtaining approval from the Ethical Committee of Menoufia University Hospital. Informed written consent was obtained from the parents of the children involved in the study.

Comparison of oral iron chelators in the management of transfusion-dependent β-thalassemia major based on serum ferritin and liver enzymes

Background Excess iron deriving from a chronic transfusion and dietary intake increases the risk for cardiac complications in β-thalassemia major patients. Deferiprone and deferasirox are commonly prescribed to thalassemic patients who are at risk of iron overload. This study aimed to compare the performance and toxicity of deferiprone and deferasirox in β-thalassemia major patients. Methods A cross-sectional observation was performed on 102 patients with β-thalassemia major. Serum ferritin along with total, indirect, and direct bilirubin levels were measured. Levels of liver enzymes, transaminase (ALT), and aspartate transaminase (AST), were also determined. Ferritin correlations with serum ALT, AST, and total bilirubin were constructed based on Spearman’s rank correlation. Statistical differences based on the serum parameters were analyzed between deferiprone and deferasirox groups. The differences of iron chelators’ effects between those receiving short-term (≤7 years) and long-term (&gt;7 years) blood transfusion were also analyzed. Results The averaged levels of bilirubin, ALT, AST, and ferritin were found to be high. Ferritin was positively correlated with ALT (r=0.508 and p&lt;0.001) and AST ((r=0.569; p&lt;0.001). There was no statistical difference in ferritin levels between the deferiprone and deferasirox groups (p=0.776). However, higher total bilirubin and ALT were observed in the deferasirox group than in the deferiprone group (p=0.001 and 0.022, respectively). Total (p&lt;0.001), indirect (p&lt;0.001), and direct bilirubin levels (p=0.015) were significantly higher in patients with long-term transfusions than those receiving short-term transfusions. Higher ferritin was found with a statistical significance of p=0.008 in the long-term transfusions group. Conclusions Ferritin is high in people with transfusion-dependent β-thalassemia major and positively correlated with ALT and AST. Deferasirox might pose a higher risk of developing hepatic injury as compared with deferiprone. Yet, no significant change of deferasirox efficacy (based on ferritin level) was found between those receiving short-term and long-term transfusions.

Gene Therapy of Transfusion-Dependent β-Thalassemia Patients with Quick Engraftment of Reinfused Hematopoietic Stem Cells: An Investigator-Initiated Trial of KL003

Introduction In recent years, autologous hematopoietic stem cell (HSC)-based gene therapy has emerged as one of the most promising curative therapies for the treatment of severe hereditary anemia, including β-thalassemia major. Although several clinical trials of gene therapy for β-thalassemia major patients have been completed in developed countries, clinical data of gene therapy remain scarce for patients in developing countries. These patients are often in poor clinical condition because of severe iron overload and insufficient blood transfusion due to limited blood supply. They account for the majority of the β-thalassemia major patients in developing countries. Unlike in developed countries, most β-thalassemia major patients in developing countries cannot survive to adulthood as a consequence of irregular treatments due to the limitation of medical facilities and/or personal financial conditions. Methods We conducted a non-randomized, single-dose, open-label investigator-initiated clinical trial (ChiCTR2200055565) in representative patients in southern China, including those with ferritin above 5000 µg/L. Among the 11 β-thalassemia major patients (aged 6-22) we enrolled, 6 of the patients were in poor clinical conditions (e.g., medium (3000-5000 µg/L ferritin) to severe (&amp;gt;5000 µg/L ferritin) iron overload) due to inconsistent blood transfusions and iron chelation therapy before enrollment (Table). We treated patients using their own HSCs after transduced ex vivo with KL003, a lentiviral vector expressing a functional β-globin gene. We then monitored patients closely for safety and evaluated efficacy of KL003, including stem cell engraftment, hematopoietic reconstitution/recovery, and blood transfusion requirement. Results Blood transfusion was no longer needed for all 11 patients from median day 14 (range: 10-30 days) after treatment. The longest duration of no blood transfusion has been 18 months. The median engraftment time was 14 days for neutrophils (range: 8-15 days) and 14 days (range: 11-33 days) for platelets. This is a significant improvement compared with much longer engraftment time from previous autologous HSC-based gene therapies in the literature, which were around 4 weeks for neutrophils and 6 weeks for platelets. It is worth noting that the platelet engraftment time (33 days) for patient No. 07, who had a severe iron overload, was much longer than others (Table). This may represent a common challenge for treating patients with severe iron overload. The safety profile was consistent with that typical of busulfan-based myeloablation conditioning. There were no severe adverse events associated with KL003. Conclusion Our clinical trial results demonstrate potentially curative results in β-thalassemia major patients, including those in poor clinical condition. In addition, the optimized transduction process of HSCs may have contributed to maintaining stemness of HSCs, which is essential for quick engraftment and often gets lost during ex vivo manipulation. This has led to significantly faster engraftment and better efficacy. Thus, KL003 could be a potential functional cure for β-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.

Hepatic Iron Deposition Quantification in Patients with β-Thalassemia Using Magnetic Resonance Imaging

Background: Detection and quantification of liver iron overload are significant to initiate treatment and monitoring of iron overload. This study aimed to quantify liver iron deposits in β-thalassemia major patients using MRI T2* and its correlation with age and heart iron deposition. Methods and Results: This retrospective study included 54 records of patients between 5-16 years of age with hepatic iron deposition due to β-thalassemia major. Data were collected from MRI reports in Picture Archiving and Communication Systems-Radiology Information System (PACS-RIS) and serum ferritin (SF) test results obtained from Hospital Information Systems and written into a dedicated datasheet. The information was recorded on a data collection sheet. The datasheet included all the required data, demographic data, lab results, T2* mapping for iron deposition in the liver and heart, and liver measurements. All subjects had high SF (from 1120 to 9850 ng/ml) with an average of 4317.93±2779.9 ng/ml. Age and SF correlated positively (r=0.368, P=0.0006). A negative correlation was observed between SF and liver T2* (r= -0578, P=0.000) (Table 3), whereas between liver T2* and heart T2* correlation had a positive direction (r= 0.329, P=0.015) Conclusion: MRI provides accurate, non-invasive, valid, and repeatable techniques, which are more acceptable to patients for assessing iron load. Furthermore, MRI T2* methods measure iron overload within the target organ precisely.

Factors Related to Reduced Bone Density in β-Thalassemia Major Patients: Mazandaran Thalassemia Registry

Introduction: OsteoPenia and osteoPorosis are known to be one of the main comPlications of β-thalassemia major (β-TM). The aim of this study was to determine the factors associated with decreased bone density of these Patients.&#x0D; Methods: Lumbar and femoral neck bone mineral density (BMD) in β-TM Patients characterized via Dual-energy X-ray absorPtiometry (DXA) to PinPoint the association of iron chelators, diabetes mellitus, serum ferritin above 3000 ng/mL, hemoglobin below 8 gr/dl, using hydroxyurea, liver siderosis and moderate to severe hePatic and cardiac siderosis with BMD. The information was collected from the thalassemia registry in 2019 and statistical analysis was Performed by STATA-13 software.&#x0D; Results: Out of 1959 ParticiPants with β-thalassemia major registered in the registry, 139 ones (7.09%) had bone mineral density (53 males and 86 females). The Prevalence of abnormal bone density in the lumbar and femoral neck was (52.48 to 47.66) 57.5 and (40.18 to 57.52) 48.85 Percent, resPectively. After adjusting for the effects of Possible interventions, the odds ratio of abnormal bone density in the Patients consuming hydroxyurea and deferasirox were 0.24 (0.03 to 1.73) and 0.25 (0.03 to 1.69), resPectively. The highest odds were 8.21 (0.18 to 360.22), and 6.72 (0.60 to 74.83) for moderate to severe cardiac and hePatic dePosition, resPectively.&#x0D; Conclusion: The Prevalence of osteoPenia and osteoPorosis is high among thalassemia major Patients. ConsumPtion of hydroxyurea and deferasirox is the most imPortant Protective factor and moderate to severe cardiac and hePatic siderosis are the most imPortant risk factors for abnormal bone density.

Mutational analysis of hemoglobin genes and functional characterization of detected variants, through in-silico analysis, in Pakistani beta-thalassemia major patients

Thalassemia is one of the most prevalent genetic disorders worldwide. The present study aimed to explore the mutational spectrum of all hemoglobin (HB) encoding genes and to identify the potentially damaging and pathogenic variants in the beta (β)-thalassemia major patients and thalassemia minor carriers of Southern Punjab, Pakistan. A total of 49 β-thalassemia major patients and 49 carrier samples were screened for the identification of HBA1, HBA2, HBB, HBD, HBE1, HBG1 and HBG2 variants by NGS. PCR was performed for the amplification of HB encoding genes and the amplified product of 13 patients and 7 carrier samples were processed for the Sanger sequencing. Various bioinformatics tools and databases were employed to reveal the functional impact and pathogenicity potential of the observed variants. Results depicted a total of 20 variants of HB-related genes by NGS and 5 by Sanger sequencing in thalassemia patients. While 20 variants by NGS and 3 by Sanger were detected in carriers. Few known genetic variants of HB-encoding genes are being reported for the first time in Pakistani thalassemia patients and carriers. However, two novel HBB variants c.375A>C (p.P125P) and c.*61T>G and a novel variant of HBE1 (c.37A>T (p.T13S)) were also documented. Pathogenicity analysis predicted the pathogenic potential of HBB variants (c.47G>A (p.W16*), c.27-28insG (p. S10fs), and c.92+5G>C) for β thalassemia. The study of functional impact indicated that these HBB variants result in the premature termination of translation leading to the loss of functional β-globin protein. It is therefore suggested that the pathogenic HBB variants, identified during present study, can be employed for the diagnosis, carrier screening, and planning therapy of thalassemia.

Evaluation of craniofacial anthropometry of children with β-thalassemia major in the eastern Anatolia: a case-control study.

The present study aims to compare β-thalassemia major patients and healthy individuals in terms of anthropometric characteristics and changes in craniofacial profile. Craniofacial anthropometric measurements were performed on a total of 422 subjects (199 β-thalassemia major patients and 223 healthy individuals) by using a millimetric caliper and tape measure on 19 anthropometric parameters (8 horizontal, 10 vertical, and 1 head circumference) in cranial, facial, nasal, orolabial, and orbital zones. The difference between the orbital, nasal, and orolabial zone parameters of healthy subjects and β-thalassemia major patients was found to be statistically significant (p < 0.05). There was no statistically significant difference between the groups in terms of head circumference in the cranial zone and total facial height in facial zone (n-gn) values (p˃0.05). In intragroup comparison between females and males with β-thalassemia, statistically significant differences were found in forehead width (ft-ft), forehead height (tr-gl), right eye width (R ex-ex), and upper lip height (sn-stm) (p < 0.05). Understanding the craniofacial profile changes in β-thalassemia major patients and increasing our knowledge about the relationship between the course and severity of disease and the level of these changes would contribute to the advancements in diagnoses to be made in facial and jaw zones of these patients and in the treatment plans. We believe that the analysis and results of the craniofacial anthropometric data obtained in the study will contribute to the diagnosis and treatment processes of patients with β-thalassemia major in areas of expertise such as craniofacial surgery, orthodontics, and hemato-oncology.

Clinical outcome and humoral immune responses of β-thalassemia major patients with severe iron overload to SARS-CoV-2 infection and vaccination: a prospective cohort study

COVID-19 has raised special concern for patients with β-thalassemia major (β-TM) due to frequent comorbidities, regular blood transfusions, and iron overload. However, the exact implications of COVID-19 for patients with β-TM remain uncertain. We aimed to explore the COVID-19 incidence and severity, and the serological response to SARS-CoV-2 infection and vaccination in patients with β-TM. Patients with β-TM (n=105) and age-matched healthy controls, all individuals of all control groups were health care workers of the hospital, were prospectively enrolled at the haematology department of Al-Shifa hospital in the Gaza Strip from January 1st, 2021 to December 31st, 2021. Data on COVID-19 incidence and severity were analysed, with Alpha, Beta, and Delta SARS-CoV-2 variants dominating at that time. Anti-SARS-CoV-2 IgG antibody levels were measured and compared between study groups. Patients with β-TM showed a higher incidence of SARS-CoV-2 infection than the general population (61.9% vs. 7.1%, p<0.0001). Most patients with β-TM had asymptomatic (70.8%) or mild disease (26.1%), with no fatalities recorded. COVID-19 illness was more severe among female than male patients with β-TM. Anti-SARS-CoV-2 IgG antibodies were significantly higher in symptomatic patients with β-TM than controls post-infection (geometric mean÷geometric standard deviation 1299.0÷3.3 vs. 555.7÷2.4 AU/mL, p=0.009) and post-vaccination (8404.0÷3.9 vs. 2785.6÷5.0 AU/mL, p=0.015). Similar responses were observed when comparing splenectomised to non-splenectomised (both asymptomatic and symptomatic) patients with β-TM post-infection (595.4÷3.9 vs. 280.7÷3.5 AU/mL, p=0.005) and post-vaccination (13,778.2÷3.2 vs. 4961.8÷4.1 AU/mL, p=0.045). This distinctive β-TM cohort exhibited a high susceptibility to SARS-CoV-2 infection but mild disease course. Our findings support favourable serological responses to SARS-CoV-2 infection and to vaccination in patients with β-TM, indicating a potential interplay between iron availability and COVID-19-related immunity. This study was funded by Mr. Hosam and Wasim s. El Helou.

Evaluating von Willebrand factor and ADAMTS13 levels in thalassemia major patients and assessing a possible association with Thrombospondin-1.

Alterations in the endothelium and endothelial adhesion proteins such as von Willebrand factor (vWF) play major roles in hypercoagulability in thalassemia. vWF protein release leads to platelet aggregation and thrombi formation at the site of vascular injury. It is then degraded by the proteolytic enzyme ADAMTS13. Thrombospondin-1 is a multifactorial glycoprotein, which was reported to compete with ADAMTS13 for sites of vWF proteolysis. In this study, levels of vWF, ADAMTS13, and TSP-1 proteins were determined in β-thalassemia major patients. A possible association between TSP-1 and vWF and ADAMTS-13 was also evaluated. The study was conducted on 80 β-thalassemia major patients and 80 age and sex matched healthy controls. The 80 patients were sub-divided into two groups; splenectomised and non-splenectomised. vWF, ADAMTS13 and TSP-1 plasma level were measured using ELISA technique. There was no significant difference in vWF and TSP-1 levels between patients and controls (p > 0.05). However, ADAMTS13 levels and ADAMTS13 activity/vWF antigen ratio were significantly higher in patients compared to controls (p < 0.05). VWF antigen and TSP-1 level were significantly higher in splenectomised patients (p = 0.025 and p < 0.001, respectively). We also observed a significant decrease in ADAMTS13 activity/vWF antigen ratio among splenectomised compared to non- splenectomised patients (p = 0.019). Correlation analysis showed a significant negative correlation between TSP-1 and vWF Collagen Binding Activity (r = -0.394, p = 0.021) and a positive correlation with ADAMTS13 activity/vWF antigen ratio (r = 0.356, p = 0.039) in splenectomised compared to non- splenectomised patients. Our findings highlight the adequacy of patient management protocols for β-TM in Kuwait as patients presented with comparable levels of platelets, vWF and TSP-1 compared to normal controls. The reported increase in ADAMTS13 in patients may be required to maintain normal levels of vWF. Although no active thrombotic episodes were reported at the time of the study, the significant rise in platelets, vWF:Ag and TSP-1 levels in splenectomised patients may indicate a tendency towards hypercoagulability. Monitoring of splenectomised patients is recommended.

Pattern and clinical correlates of renal iron deposition in adult beta-thalassemia major patients.

We evaluated pattern and clinical correlates of renal T2* measurements in adult β-thalassemia major (β-TM) patients. Ninety β-TM patients (48 females, 38.15 ± 7.94years), consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia network, underwent T2* magnetic resonance imaging (MRI) for quantification of iron overload (IO) in kidneys, liver, pancreas, and heart. Ten (11.1%) patients showed renal IO (T2* < 31ms). Global kidney T2* values did not show a correlation with gender, age, splenectomy, regular transfusions or chelation starting age, pre-transfusion hemoglobin, and serum ferritin levels. Global kidney T2* values showed an inverse correlation with MRI liver iron concentration (LIC) values (R = - 0.349; p = 0.001) and a positive correlation with global pancreas T2* values (R = 0.212; p = 0.045). Frequency of renal IO was significantly higher in patients with cardiac IO than in patients without cardiac IO (50.0% vs. 6.3%; p = 0.001). A significant inverse association was detected between global kidneys T2* values and lactate dehydrogenase (LDH) (R = - 0.529; p < 0.0001). In multivariate regression analysis, MRI LIC and LDH were the strongest predictors of global kidney T2* values. A MRI LIC > 4.83mg/g dw predicted the presence of renal IO (sensitivity = 90.0%; specificity = 61.2%). Global kidney T2* values were inversely correlated with uric acid (R = - 0.269; p = 0.025). In conclusion, in adult β-TM patients, renal iron deposition is not common and is linked to both hemolysis and total body iron overload.

Assessment of glucose homeostasis in young adult female β-thalassemia major patients (β-TM) with acquired hypogonadotropic hypogonadism (AHH) never treated with sex steroids compared to eugonadal β-TM patients with spontaneous menstrual cycles.

Acquired ypogonadotropic hypogonadism (AHH) is the most prevalent endocrine complication in thalassemia major (TM). Considering the detrimental effect of estrogen deficiency on glucose metabolism, the ICET-A Network promoted a retrospective study on the long-term effects of estrogen deficiency on glucose homeostasis in female β-TM patients with HH without hormonal replacement therapy (HRT). Seventeen β-TM patients with AHH (4 had arrested puberty; Tanners' breast stage 2-3), never treated with sex steroids, and 11 eugonadal β-TM patients with spontaneous menstrual cycles at the time of referral were studied. A standard 3-h OGTT was performed in the morning, after an overnight fast. Six-point plasma glucose and insulin level determinations, indices of insulin secretion and sensitivity, early-phase insulin insulinogenic index (IGI), HOMA-IR and β-cell function (HOMA-β), oral disposition index (oDI), glucose and insulin areas under the OGTT curves were evaluated. Abnormal glucose tolerance (AGT) or diabetes was observed in 15 (88.2%) of 17 patients with AHH and 6 (54.5%) of 11 patients with eumenorrhea. The difference between the two groups was statistically significant (P: 0.048). However, the group of eugonadal patients was younger compared to AHH patients (26.5 ± 4.8 years vs. 32.6 ± 6.2 years ; P: 0.010). Advanced age, severity of iron overload, splenectomy, increased ALT levels and reduced IGF-1 levels were the main clinical and laboratory risk factors for glucose dysregulation observed in β-TM with AHH compared to eugonadal β-TM patients with spontaneous menstrual cycles. These data further support the indication for an annual assessment of OGTT in patients with β-TM. We believe that a registry of subjects with hypogonadism is necessary for a better understanding of the long-term consequences of this condition and refining treatment options.

Correlation between Adherence Therapy of Iron Chelation Levels with Serum Ferritin Levels in Major Beta-Thalassemia Patients at Kediri District General Hospital

Repeated transfusions, increased absorption of iron, and ineffective erythropoiesis in patients with B thalassemia major cause iron overload, characterized by increased ferritin levels. Iron chelation therapy is needed to overcome iron overload in patients with beta-thalassemia major. The level of adherence affects the success of iron chelation therapy. This study aims to determine the relationship between adherence to iron chelation treatment and serum ferritin levels in patients with thalassemia beta major at Kediri District General Hospital. This type of research is an observational analytic with a cross-sectional design conducted on 17 subjects of B-thalassemia major patients at Pediatric Health Sciences (IKA) RSUD Kediri Regency who met the inclusion and exclusion criteria in December 2022-January 2023. The interviews used the Morisky Medication Adherence Scale questionnaire. -8, while the serum ferritin examination was obtained from the patient's medical record. There were 17 respondents who obeyed 11.76%; the non-compliant category was carried out by Spearman's correlation test and obtained a value of p = 0.01 and a value of r = -0.559. This shows significant results, and there is a moderate correlation between the level of adherence to iron chelation treatment and serum ferritin levels in beta-thalassemia major patients at Kediri District Hospital.

Is the total number of blood transfusion in β-thalassemia major patients can be used to assess their serum ferritin levels ?

β-thalassemia is an inherited blood disorder in hemoglobin synthesis that results in anemia, growth retardation and certain pathological changes. The treatment of choice for β-thalassemia is the repeated blood transfusion, but unfortunately it results in an iron overload with additional risk factors. The present study aims to evaluate iron profile in transfusion dependent β-thalassemia patients and the effects of repeated blood transfusion on serum ferritin level and the possibility of using the total number of blood transfusion to predict serum ferritin level. 40 transfusion dependent β-thalassemia patients were included in the present study all dependent on blood transfusion only with age range 1-4 years old. A control group of 20 apparently healthy children with age range 1-4 years old was used for comparison. Blood sample of 5 ml was collected from each individual and tested for serum levels of iron, TIBC, % saturation, and serum ferritin. The present study revealed significant changes in the levels of iron profile parameters between patients and control subjects manifested by significantly elevated serum iron and ferritin levels with significantly decreased serum TIBC. Iron status and iron overload in transfusion dependent β-thalassemia patients revealed a significant correlation between serum ferritin level and the number of transfused RBCs units. However this correlation is a rough correlation and some times unpredictable and it could not be used to assess the level of serum ferritin as used by some physicians.