Beta Thalassemia Major Research Articles

Studying the some biochemical parameters for thalassemia patients in AL-Najaf province

The current study aims to study some biochemical indicators for thalassemia patients in the Najaf governorate, and the study included 25 patients with major beta thalassemia during the period from November 2019 to February 2020 and their ages ranged between (2 - 65) years and 15 healthy people who arenot He had genetic blood diseases and their ages ranged between (2-65) years. The results of the study showed that there are in some biochemical indicators, as there was a significant increase in the level of the enzyme of liver function ALT that was the focus in patients 23.74 ± 29.53 U\L and in healthy people it was 4.61 ± 11.67U\L Also, the creatinine concentration patients 9.92 ± 26.08 mmol\L and in healthy was, 68.06 ± 51.54 mmol\L, Except for urea, we notice that there was a decrease in its concentration in patients 0.89 ± 3.96 mmol\L and in healthy was 1.03 ± 2.36 mmol\L, There was an increase in the concentration of iron in the blood in patients 382.05 ±64.37 Umol\L And in healthy was 9.48 ± 61.36 Umol\L, as well as a decrease in the concentration of glucose in patients and an increase in healthy people

Challenges of Blood Transfusions in β-Thalassemia during COVID-19 Pandemic in Low Middle-Income Country

Wuhan, Hubei province, China, was recognized as the center of an epidemic of pneumonia of unknown origin in December 2019. Ultimately, intense focus on the disease was raised in China and globally. Consequently, on January 7, 2020, Chinese research scientists identified the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an affected patient in Wuhan. Several members of this family circulate in humans, causing a wide range of disease conditions ranging from mild to life-threatening Beta thalassemia is a congenital hereditary disorder of inefficient erythropoiesis that leads to peripheral red cell breakdown due to defective β-globin series. The severity of the disease depends on multiple genetic and environmental factors. Individuals with beta-thalassemia are classified based on their transfusion demands as having transfusion-dependent thalassemia (TDT) or non-transfusion-dependent thalassemia (NTDT). Routine transfusion remains the recommended standard management for beta-thalassemia, as it efficiently controls the thalassemia symptoms. If left untreated, Beta thalassemia major (BTM) can eventually induce spleen enlargement, deformation of bone due to bone marrow growth, and heart failure due to severe anemia.

Effectiveness of an Educational Program on Parents' Knowledge about Home Health Care Management to Children with Beta Thalassemia-Major at Thalassemia Center in Al-Zahra Teaching Hospital for Maternity and Children in Al-Najaf City

Background Thalassemia is a hereditary condition that affects the formation of globin chains. Children with βeta-thalassemia major have a complete absence of globin production. βeta thalassemia- major is a severe type of disease that require life-long blood transfusions for survival. Objectives: To evaluate the effectiveness of an educational program on parents' knowledge regarding home health care management related to children with Beta Thalassemia-Major Methodology: A quasi experimental study was carried out at Thalassemia Center in Al-Najaf City during the periods 25 February 2021 to 20 March 2022. Non-probability (purposive) sample of (70) parents were selected from thalassemia center (38 mothers and 32 fathers). Results: The study findings show that there are high significant difference in overall main domains relating parents' knowledge of beta-thalassemia major between pre and post-tests 1&2 in the study group. In addition there is a statistical relationship between parental knowledge with regard to their age. Also there is high statistical significant relationship during parents’ knowledge with regard to their educational level Conclusion: The study finds that the efficacy of an educational program to improving parents' knowledge of home health care management for children with β-Thalassemia Major is high Keyword: Educational Program, Beta thalassemia, Children, AL-Najaf City

Cardiac iron overload detection using longitudinal strain in asymptomatic children with beta thalassemia major.

Cardiomyopathy mediated by iron disposition in cardiomyocytes is a dreadful cause of morbidity and mortality in patients with beta thalassemia major (BTM). Conventional transthoracic echocardiography (TTE) parameters are preserved at late stages of cardiomyopathy induced by iron overload. Therefore, cardiac imaging modalities based on myocardial deformation such as strain imaging are used for early detection of cardiac iron overload. To demonstrate the contribution of longitudinal strain (LS) in early detection of cardiac iron overload in children with BTM. Sixty children (30 children with BTM and 30 healthy controls) were enrolled in this study. Conventional TTE study was performed in both patient and control groups. LV regional longitudinal strain (RLS) were determined and compared between the two study groups. Mean age was 10.4 ± 5years in BTM group compared to 10.2 ± 5years in control group (p = 0.876). Compared to control group, there was no significant difference in conventional TTE parameters except for indexed left atrium (LA) area and volume. LA was significantly larger in BTM children (27.59 ± 13.1ml/m2 vs. 18.23 ± 4.33ml/m2, p = 0.001). RLS was lower in anterior, septal and inferior walls in basal and middle segments of LV in BTM group while there was no significant difference in RLS in apical segment between the two groups (-27.30 ± 5.1 vs.-28.83 ± 4.33, p = 0.22). In asymptomatic BMT children with normal conventional TTE parameters, LS could be used for the detection of subclinical myocardial dysfunction.

Two trade names of deferasirox (Osveral® and Exjade®) in reduction of iron overload parameters in major beta-thalassemia patients: A randomized open labeled clinical trial.

Background:Beta-thalassemia major patients typically require chronic transfusion and iron-chelating agents to reduce serum iron overload. Osveral® is an available Iranian brand name of deferasirox used by majority of thalassemic patients. The aim of this study was to compare the efficacy of Osveral® vs. Exjade® in major beta- thalassemia patients.Methods:In this randomized clinical trial, all patients received a single daily dose of 30 mg/kg either of Osveral® or Exjade® for 6 months. Primary outcome was the mean of bimonthly changes in serum ferritin concentration and secondary outcomes included mean changes of heart and liver MRI T2* after a year.Results:Finally, 80 patients completed the study. The mean serum ferritin level at the end of sixth month significantly decreased in Osveral® and Exjade® groups (p<0.01). After a year, means cardiac MRI T2* in Osveral® group were changed from 25.9±9.6 ms to 25.4±9.7 ms and in Exjade® group from 24.8±9.2 ms to 26.9±5.9 ms, with no significant difference (P=0.43). Mean liver MRI T2* for Osveral® and Exjade® groups were 8.6±6.4 ms (baseline 6.3±4.7) and 6.3±4 ms (baseline 4.9±3.5), respectively and there was no significant difference between two study arms (P=0.1).Conclusion:Osveral® decreased significantly the serum ferritin level and improved heart and liver iron overload as efficient as Exjade®. It can be a suitable cost-effective alternative agent in beta-thalassemia major patients.

T2-weighted cardiovascular magnetic resonance and echocardiographic arterial elasticity criteria for monitoring cardiac siderosis in patients with beta-thalassemia major.

Background:Despite the availability of iron chelators, toxicity due to increased iron load is the leading cause of death in thalassemia major patients, especially in Iran. This study was performed to determine the association between cardiovascular magnetic resonance using T2-weighted sequences (CMR T2*) and diagnostic value of echocardiographic arterial elasticity in major beta-thalassemia patients without cardiac symptoms in Isfahan, Iran, in 2019 and 2021.Materials and Methods:This cross-sectional study assessed the association between CMR T2*, advanced echocardiographic arterial elasticity criteria, and serum ferritin in 67 patients with major beta-thalassemia patients without cardiac symptoms at Chamran Cardiovascular, Medical, and Research Center in Isfahan, Iran, in 2019–2021. Data analysis was performed among the 67 patients using SPSS, version 24.0 (Statistical Procedures for Social Sciences, Chicago, Illinois, USA). Spearman's rank test was used to assess the correlation between T2*CMR, echocardiographic arterial elasticity criteria, and ferritin. All parameters are presented as mean ± standard deviation. The results were considered statistically significant at P < 0.05.Results:There was a positive correlation between CMR T2* and arterial elastance index (P = 0.035, r = 0.258), according to the Spearman test. In addition, CMR T2* was not correlated with the serum ferritin (P = 0.158, r = 0.201).Conclusion:Totally, according to the obtained results, it may be concluded that the arterial elastance index from echocardiography and the CMR T2* may be indicators of myocardial iron overload in patients with major beta-thalassemia patients without cardiac symptoms.

Effect of low dose pamidronate in the treatment of thalassemia-induced osteoporosis

Introduction: Thalassemia is the most common genetic defect, globally affecting about 200 million individuals. Increased longevity in transfusion-dependent thalassemia patients is accompanied by complications such as osteopenia, osteoporosis and skeletal disabilities. In this regard, increased bone reabsorption in beta-thalassemia has led to the administration of bisphosphonates for these patients. Objectives: Although there is growing consensus on the effectiveness of pamidronate in thalassemia osteoporosis, the findings about the dosage and duration of pamidronate are inconsistent. Accordingly, the present study aimed to assess the impact of low-dose pamidronate on the bone mineral density (BMD) of major beta-thalassemia patients. Patients and Methods: In this study, the participants encompassed 20 transfusion-dependent major thalassemia patients with Z-score&lt; -2.5 in bone mineral densitometry. Bone density was determined in the lumbar vertebras and hip by using dual X-ray absorptiometry. Pamidronate was administered intravenously in monthly dosage of 1 mg/kg over six months. Results: According to the findings, the participants’ mean age was 16.55±3.15 years (Range: 10-25 years). The baseline mean of Z-score for lumbar vertebras was -2.92±1.14 and reached -1.95±1.2 after six months (P&lt;0.001). Moreover, the baseline mean of Z-score for the hip region was -2.00 (0.65) and reached -1.55 (0.77). Conclusion: The dosages of 1 mg/kg over six months had a statistically significant effect on bone density and improved Z-scores of lumbar vertebrae and hip bone density by 45% and 20%, respectively.

Bleeding Versus Thrombotic Tendency in Young Children With Beta-Thalassemia Major.

IntroductionBleeding and thrombotic events are known to occur in beta-thalassemia major (BTM) patients and have been attributed to hepatic iron overload associated with multiple blood transfusions. We evaluated hemostatic parameters in children with BTM who had no previous history of bleeding or thrombotic episodes.Materials and MethodsHemostatic parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), platelet aggregation, protein C and S, iron profile, and liver function tests were evaluated in 54 children (median age = 12 months, age range = 4-144 months) with BTM and 15 age and sex-matched controls.ResultsThe mean PT and APTT of patients were significantly higher (P=0.016 and P <.001) than that of controls. Mean protein C, protein S activity and platelet aggregability with adenosine 5-diphosphate (ADP) as an agonist in patients were significantly lower (P <.001, P <.001 and P=0.007, respectively) than that in controls. Mean serum ferritin in BTM children was not significantly elevated to be associated with hepatic dysfunction.ConclusionDeranged hemostatic parameters indicative of bleeding and thrombotic tendencies are observed in BTM children from an early age and may not be solely due to hyperferritinemia-associated hepatic dysfunction. Despite the presence of deranged hemostatic parameters, a state of balance exists between bleeding and thrombosis, and an imbalance may lead to bleeding or thrombotic events at a later age.

Comparing measurement properties of EQ-5D-Y-3L and EQ-5D-Y-5L in paediatric patients

BackgroundThe adult versions EQ-5D-3L and EQ-5D-5L have been extensive compared. This is not the case for the EQ-5D youth versions. The study aim was to compare the measurement properties and responsiveness of EQ-5D-Y-3L and EQ-5D-Y-5L in paediatric patients.MethodsA sample of patients 8–16 years old with different diseases and a wide range of disease severity was asked to complete EQ-5D-Y-3L, EQ-5D-Y-5L, PedsQL Generic Core Scale, and selected, appropriate disease-specific instruments, three times. EQ-5D-Y-3L and EQ-5D-Y-5L were compared in terms of: feasibility, (re-)distribution properties, discriminatory power, convergent validity, test–retest reliability, and responsiveness.Results286 participating patients suffered from one of the following diseases: major beta-thalassemia, haemophilia, acute lymphoblastic leukaemia, acute illness. Missing responses were comparable between versions of the EQ-5D-Y, suggesting comparable feasibility. The number of patients in the best health state (level profile 11111) was equal in both EQ-5D-Y versions. The projection of EQ-5D-Y-3L scores onto EQ-5D-Y-5L for all dimensions showed that the two additional levels in EQ-5D-Y-5L slightly improved the accuracy of patients in reporting their problems, especially if severe. Convergent validity with PedsQL and disease-specific measures showed that the two EQ-5D-Y versions performed about equally. Test–retest reliability (EQ-5D-Y-3L 0.78 vs EQ-5D-Y-5L 0.84), and sensitivity for detecting health changes, were both better in EQ-5D-Y-5L.ConclusionsExtending the number of levels did not give clear superiority to EQ-5D-Y-5L over EQ-5D-Y-3L based on the criteria assessed in this study. However, increasing the number of levels benefitted EQ-5D-Y performance in the measurement of moderate to severe problems and especially in longitudinal study designs.

Evaluation of the Thyroid Status and Types of Thyroid Dysfunction in Beta-Thalassemia Major Patients More Than 9 Years of Age in Wassit, Iraq 2020

Background: Hypothyroidism is one of the commonest endocrine complications that can happen in patients with Beta-Thalassemia Major (BTM) above nine years old which may pass hidden and untreated for years. Aim: To evaluate the thyroid status and types of thyroid dysfunction in Beta-Thalassemia Major Patients above 9 years of age. Method: A Cross-Sectional study was performed on sixty-six randomly selected patients above 12 years of age with BTM in Al-Kut Heriditory Blood Disease Center at Wassit province from March to August 2020. Thyroid function tests were done (TSH, T3, and T4) to detect the thyroid status and identify patients with thyroid dysfunction and determine the type of hypothyroidism (Primary, central, Subclinical). Data collected include Age, Sex, weight, height, Serum ferritin and mean hemoglobin level, Type of chelation therapy, dose, compliance, and frequency of blood transfusion, other diseases such as Diabetes Mellitus, HCV, HBV, HIV, and Heart Failure were evaluated statistically. Results: In the studied patients, Thirty-one patients (46.96%) were found to have hypothyroidism;( Seven of them (10.6%) had primary hypothyroidism, Sixteen(24.2%) had subclinical hypothyroidism and eight (12.1%) had central hypothyroidism). Twenty-one (67.74 %) patients with Hypothyroidism were found to have stunted height or short stature (with significant p.value 0.03) from the 13 (41.9%) who had subclinical hypothyroidism. By Pearson correlation, increasing serum ferritin levels significantly affect decreasing thyroxin (T4) levels with inverse correlation (P value 0.0001), (r)= -0.45. Conclusion: in this study, there was a high prevalence of hypothyroidism in BTM and subclinical hypothyroidism is the most common type, which signifies the importance of regular screening and close supervision especially when high ferritin and or short stature are present.

Comprehensive Review: Extramedullary Hematopoiesis in Patients with Beta Thalassemia Major (transfusion dependent thalassemia)

AbstractIntroduction:Thalassemia is one of the most common hemoglobinopathies, with around 5% of world's population expected to have some degree and type of thalassemia. Beta thalassemia (BT) occurs due to a deficient production of the beta-globin chain of hemoglobin. BT is classified into minor, intermedia, and major, defined by their clinical and laboratory findings. Extramedullary hematopoiesis is one of the complications of BT, primarily seen in minor/intermedia subtypes. EMH is the production of blood cells outside the marrow as a compensatory response to longstanding hypoxia. Due to chronic transfusions, it is not expected in patients with beta thalassemia major (BTM). However, there are multiple case reports of EMH in BTM. The incidence of EMH in BTM is thought to be <1%. However, given the increasing cases, it seems that the true incidence is much higher than expected. This systematic review aims to pool the available data and provide cumulative evidence on the occurrence of EMH in BTM patients.Methods:This is a systematic review of case reports, series, and retrospective studies that presented data on the occurrence of EMH in BTM patients. Data were recorded and analyzed in Microsoft Excel 2016 and SPSS 26. The protocol has been registered in PROSPERO: CRD42021242943.Results:Data from 253 cases of EMH in BTM patients were extracted from 2 retrospective studies and 71 case reports (some of the descriptive data from case reports and most of the descriptive data from retrospective studies was missing). The mean age at presentation was 35.3 +/- 0.5 years. Males constituted 57.7% of the total population. Mean hemoglobin at presentation with EMH was 8.2 +/- 2.1 mg/dL. Lower limb weakness was the most common presenting feature (N=23). Other features included localized pain, urinary incontinence, and an incidental finding of EMH. Magnetic resonance imaging (MRI) was the most widely used diagnostic modality (N=226). However, computed tomography scans, positron emission tomography scans, tissue biopsy, myelograms, and X-rays were also used to diagnose EMH. Various treatments were reported either alone or in combination. Overall, blood transfusion was the commonest reported treatment (N=30), followed by radiotherapy (N=20), surgery (N=15), hydroxyurea (N=12), steroids (N=6), and exchange transfusion (N=2). An outcome was reported in 20% of patients, all recovered, with no reported mortality.Conclusion:EMH is considered a rare phenomenon in BTM patients. However, there are many cases reported in which EMH occurred in BTM despite chronic blood transfusions. EMH can occur in any organ system and can present with a varied clinical feature. MRI can effectively diagnose EMH, and conservative management is reported to have similar results compared to invasive treatments. More extensive studies, focusing especially on outcomes, are required to enhance the guidelines on managing EMH in patients with BTM. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Protocol for extramedullary hematopoiesis in patients with transfusion-dependent β-thalassemia (TDT): A systematic review.

Background and aimsThalassemia is one of the most common hemoglobinopathies, with around 5% of the world's population expected to have some degree and type of thalassemia. Beta thalassemia (BT) occurs due to a deficient production of the beta‐globin chain of hemoglobin. Extramedullary hematopoiesis (EMH) is one of the complications of BT, mainly observed in minor/intermedia subtypes. EMH is the production of blood cells outside the marrow as a compensatory response to longstanding hypoxia. Due to chronic transfusions, it is not expected in patients with beta‐thalassemia major (BTM). However, there are increasingly reported cases of EMH in BTM. The incidence of EMH in BTM is thought to be <1%. However, it seems that the true incidence is much higher than expected. This review aims to pool the available data and provide cumulative evidence on the reports of EMH in BTM patients.MethodsWe aim to conduct a systematic review via searching multiple electronic databases (PubMed, Scopus, Google Scholar) to identify eligible articles from any date up to December 2020. Eligible studies should report extramedullary hematopoiesis in BTM. Case reports, case series, observational studies with cross‐sectional or prospective research design, case‐control studies, and experimental studies will be included if found relevant. Two reviewers (FA and ES) will individually analyze the study quality using the statistical methodology and categories guided by the Cochrane Collaboration Handbook, PRISMA guidelines, and Joanna Briggs Institute checklist for case reports and series.ResultsThis study will analyze and incorporate the available evidence on EMH in BTM concerning patient demographics, sites of EMH, management, and clinical outcomes of EMH.ConclusionBy summarizing and statistically analyzing the data about EMH in BTM, this study will generate extensive knowledge on the topic for a better understanding of atypical presentations in BTM, a common hemoglobinopathy.

The correlation of cardiac biomarkers and myocardial iron overload based on T2* MRI in major beta-thalassemia.

Cardiac hemosiderosis is the primary factor to derive the pathogenesis of cardiac dysfunction in patients with transfusion dependent thalassemia. Biomarkers assessment along with T2 * MRI study could be employed to evaluate the severity of iron deposition-related damage and determination of the diagnostic and prognostic value of these inflammatory factors. The study was conducted on 62 patients (12-44years old) with major thalassemia. The patients were under regular blood transfusion and they had no signs of cardiac defects, and chronic diseases. The serum levels of inflammatory factors (NT-proBNP, CRP, Copeptin HS) were determined before routine transfusion. Cardiac iron overload was assessed by T2* MRI (within the last three months), and T2* lower than 20ms was considered as cardiac siderosis. The obtained results were analyzed using statistical methods. 92% of patients showed an increased level of hs-CRP (> 2µg/dL). All cases showed increased levels of NT-proBNP (> 150pg/mL). Only 29% of subjects showed high level of Copeptin, 25.8% of patients demonstrated cardiac siderosis based on the T2* MRI (< 20ms) results. The serum levels of inflammatory factors were not significantly correlated with cardiac siderosis. Given the obtained results, it could be deduced that the serum levels of inflammatory factors could not be exploited for early detection of cardiac siderosis in major beta-thalassemia patients.

EXTRAMEDULLARY HEMATOPOIESIS IN PATIENTS WITH TRANSFUSION DEPENDENT β-THALASSEMIA (TDT): A SYSTEMATIC REVIEW

Thalassemia is one of the most common hemoglobinopathies, with around 5% of the world's population expected to have some degree and type of thalassemia. Beta thalassemia (BT) occurs due to a deficient production of the beta-globin chain of hemoglobin. Extramedullary hematopoiesis (EMH) is one of the complications of BT, mainly observed in minor/intermedia subtypes. EMH is the production of blood cells outside the marrow as a compensatory response to longstanding hypoxia. Due to chronic transfusions, it is not expected in patients with beta-thalassemia major (BTM). However, there are increasingly reported cases of EMH in BTM. The incidence of EMH in BTM is thought to be &lt;1%. However, it seems that the true incidence is much higher than expected. This review aims to pool the available data and provide cumulative evidence on the occurrence of EMH in BTM patients. We aim to conduct a systematic review via searching multiple electronic databases (PubMed, Scopus, Google Scholar) to identify eligible articles from any date up to December 2020. Eligible studies should report extramedullary hematopoiesis in beta-thalassemia major. Case reports, case series, observational studies with cross-sectional or prospective research design, case-control studies, and experimental studies will be included if found relevant. Two reviewers (FA and ES) will individually analyze the study quality using the statistical methodology and categories guided by the Cochrane Collaboration Handbook, PRISMA guidelines, and Joanna Briggs Institute checklist for case reports and series. Data from 253 cases of EMH in BTM patients were extracted with mean age of 35.3 +/- 0.5 years. Mean hemoglobin at presentation with EMH was 8.2 +/- 2.1 mg/dL. Lower limb weakness was the most common presenting feature (N=23) (paraspinal EMH). Magnetic resonance imaging (MRI) was the most widely used diagnostic modality (N=226). Overall, blood transfusion was the commonest reported treatment (N=30), followed by radiotherapy (N=20), surgery (N=15), hydroxyurea (N=12), steroids (N=6), and exchange transfusion (N=2). An outcome was reported in 20% of patients, all recovered, with no reported mortality. EMH is considered a rare phenomenon in BTM patients. It can occur in any organ system with varied clinical features. MRI can effectively diagnose EMH, and conservative management has similar results compared to invasive treatments. Larger studies, focusing on outcomes may enhance guidelines on preventive and therapeutic strategies for managing EMH in BTM.

Indicators of glucose dysregulation and the relationship with iron overload in Chinese children with beta thalassemia major

Patients with beta thalassemia major (TM) have a higher risk of diabetes and an abnormal oral glucose tolerance test (OGTT), but there is no single agree monitoring parameter that reflects glycemic status. The possible mechanisms include iron overload and blood transfusion, but they require further investigation. This study explored the role of glycated hemoglobin A1c (HbA1c), fructosamine, and glycated albumin (GA) in evaluating the glucose dysregulation and to determine the potential relationship between iron deposition and glucose metabolism disorder in beta TM. A cross-sectional study was performed on 118 patients with beta TM and the control group consisted of 33 healthy children with no statistical differences in age, sex, and body mass index (BMI). Fast plasma glucose (FPG), fast insulin (FINS), insulin resistance index (HOMA-IRI), and insulin sensitivity index (HOMA-ISI) were compared between the patient and control groups. HbA1c, GA, fructosamine, and serum ferritin (SF) were measured in the patient group. OGTT, as well as heart and liver magnetic resonance imaging (MRI) T2*, was performed. For all statistical analyses, SPSS 21.0 was used and p < 0.05 was accepted as statistically significant. FPG, FINS, and HOMA-IRI were significantly increased while HOMA-ISI decreased in the beta TM patients when compared with those in the control group. In patients with beta TM, 17 (14.41%) of patients had been diagnosed with diabetes, while 48 (40.68%) had both impaired fasting glucose and impaired glucose tolerance. HbA1c, GA, and fructosamine were increased according to the degree of abnormal glucose metabolism. Statistically significant differences were found in age, SF, and cardiac T2* between the abnormal and normal OGTT groups. HbA1c may be used as a significant measure for monitoring glycemic levels in patients with beta TM. Furthermore, GA and fructosamine were alternative indicators of glucose status. Patients with heart iron deposition or an SF > 4000 μg/L were prone to abnormal glucose metabolism, so chelation therapy should be reinforced.

Prevalence of occult hepatitis C virus infection in beta-thalassemia major patients in Ahvaz, Iran.

Occult hepatitis C virus infection (OCI) is defined by the presence of HCV RNA in peripheral blood mononuclear cells (PBMCs) and liver tissue cells despite the absence of HCV RNA in plasma. Currently, OCI is classified into two types: seropositive OCI (anti-HCV positive and serum HCV RNA negative) and seronegative OCI (anti-HCV and serum HCV RNA negative). Beta-thalassemia is described as a blood disorder that decreases the synthesis of hemoglobin. Repeated blood transfusion is the standard treatment for patients with beta-thalassemia major (BTM), and this increases the risk of exposure to infectious agents. The aim of this study was to investigate the prevalence of OCI among BTM patients. Plasma and PBMCs were collected from 90 BTM patients who were referred to Shafa Hospital in the city of Ahvaz and were screened for HCV antibody using a commercial ELISA kit as the first step. Next, nested RT-PCR was performed on extracts of plasma and PBMCs. HCV RNA from positive PBMCs was sequenced, the sequences were aligned, and a phylogenetic tree was constructed to determine their relationship to reference sequences retrieved from the GenBank database. Seventy-nine out of 90 patients (87.8%) were negative for HCV Ab (seronegative), while 11 patients (12.2%) were seropositive. HCV RNA was found in PBMCs of four patients (66.7%) who were negative for HCV Ab (seronegative) and two patients (33.3%) who were positive for HCV Ab (seropositive). HCV RNA was not detected in plasma samples from these six patients. Six out of 90 BTM patients (6.7%) had OCI. HCV genotyping revealed that all six patients were infected with HCV subtype 3a. We found a high frequency of OCI in BTM patients, which warrants more attention, considering the importance of this infection. Further studies are needed to determine the actual prevalence of OCI in BTM patients in Iran.

Hidden brain iron content in sickle cell disease: impact on neurocognitive functions

Children with sickle cell disease (SCD) are at a high risk for neurocognitive impairment. We aim to quantitatively measure cerebral tissue R2* to investigate the brain iron deposition in children and young adults with SCD in comparison to beta thalassemia major (BTM) and healthy controls and evaluate its impact on neurocognitive functions in patients with SCD. Thirty-two SCD, fifteen BTM, and eleven controls were recruited. Multi-echo fast-gradient echo sequence brain MRI was performed, and brain R2* values of both caudate and thalamic regions were calculated. SCD patients were examined for the neurocognitive functions. SCD had high iron overload 0.30 ± 0.12mg/kg/day. 68.9% of SCD had under-threshold IQ, 12.5% had moderate to severe anxiety, and 60.8% had depression. There were no differences between SCD, BTM, and controls in brain MRI except that left thalamus R2* higher in BTM than both SCD and controls (p = 0.032). Mean right caudate R2* was higher in female than male (p = 0.044). No significant association between brain R2* and LIC or heart R2* values in SCD. Left caudate R2* directly correlate with age and HbS%, and negatively correlate with HbA% while right thalamus R2* negatively correlate with transfusion index and among SCD patients.Conclusion: Neurocognitive dysfunction in SCD could not be explained solely by brain iron overload. What is Known: • Children with sickle cell disease are at great risk of brain damage due to their irregularly shaped red blood cells that can interrupt blood flow to the brain. • There are a number of factors that have negative brain effects that result in learning difficulties, and this not only due to increase brain iron content. What is New: • Assessment of quantitative brain iron content using MRI R2* in children and young adults with SCD in comparison to beta thalassemia major and healthy controls. • Impact of brain iron content on neurocognitive functions of children and young adults with SCD.

Beta-thalassemia major alters sofosbuvir/ledipasvir exposure in Hepatitis C virus infected adolescent patients

BackgroundHepatitis C virus (HCV) infected adolescents with beta-thalassemia major (BTM) are considered a potential population for HCV micro-elimination model development where BTM may negatively impact the pharmacokinetic exposure parameters of sofosbuvir/ledipasvir (SOF/LED). ObjectivesThe study aimed at studying the effect of BTM on SOF/LED and SOF metabolite (GS-331007) pharmacokinetics. MethodsA prospective, controlled study recruiting BTM and control HCV infected adolescents (Clinicaltrials.gov identifier-NCT04353986). Pharmacokinetic exposure to GS-331007 and LED was the primary pharmacokinetic outcome. No-effect boundaries were set to 90% confidence interval (CI) of exposure geometric mean ratio (GMR) within 70–143%. Dose suitability was based on the 90% CI of exposure GMR within 50-200% compared to adults. The percentage of patients achieving sustained virologic response 12 weeks post-treatment (SVR12) was the primary efficacy endpoint. ResultsThirteen patients were enrolled per study group. All patients were included in the pharmacokinetic analysis (n=26). BTM patients showed lower GS-331007 and LED exposure that could, respectively, be as low as 45.4% and 36.1% compared to their control group. GS-331007 exposure in BTM patients was nearly half (56.8%, 90% CI 45.3–71.2%) that observed in adults. Despite that low drug exposure in 46.2% of BTM patients may alert dose unsuitability, they achieved SVR12. Moreover, patients with total bilirubin ≥1.93 mg/dL were predicted to have low GS-331007 exposure (0.913 receiver operating characteristic area under the curve with sensitivity and specificity >80%). Conclusion and RelevanceThe identified systematically lower drug exposure in BTM patients might partially explain relapses or treatment failures among BTM patients reported in other studies. BTM may be a hurdle towards implementing HCV micro-elimination model that may necessitate dose-adjustment.

Hemoglobinopathy in pediatric population: A cross sectional study at tertiary care center in Assam

Objectives: The objectives of the study were to find out the prevalence, epidemiology, and clinicohematological profile of hemoglobinopathies. Material and Methods: During the period of September 2010–August 2011, an observational study was done in the Department of Pediatrics, Assam Medical College and Hospital, Dibrugarh. Children (&lt;12 years) suffering from chronic anemia were the study population. Results: Hemoglobinopathies were noted in 72 (35.0%) out of 206 chronic anemia cases, of which sickle cell disease (SCD) was found in 23 cases (11.2%), beta-thalassemia major (BTM) in 21 cases (10.2%), hemoglobin E (HbE)-β thalassemia in 12 cases (5.8%), HbE disease was seen in 10 cases (4.8%), and HbE trait and sickle cell trait (SCT) in 3 cases each. Overall hemoglobinopathy was most commonly seen among teagarden community in Assam. Clinical presentation ranged from completely asymptomatic to congestive heart failure. In majority cases, decreased mean Hb (%) and mean corpuscular volume were found. Anisopoikilocytosis, reticulocytosis, and target cells were frequently noted in peripheral blood smear. Conclusion: Chronic anemia cases should be screened for hemoglobinopathies as these genetic disorders are commonly seen in Assam. SCD and BTM are the major types of hemoglobinopathies. Heterozygous hemoglobinopathies (HbE trait and SCT) had lesser clinical manifestations. As the definitive treatment of hemoglobinopathies is still difficult to avail in this region, genetic counseling should be considered for hemoglobinopathy patients and their families as well, to prevent new cases.

Evaluation of Transfusion-Related Hemodynamic Parameters in Patients with Beta-Thalassemia Major by Ambulatory Blood Pressure Monitoring Method

Introduction: There are very few studies on the effects of regular blood transfusions on the hemodynamic organization of patients with Beta-Thalassemia Major (BTM). Ambulatory Blood Pressure Monitoring is method that evaluates fluctuations in day-night periods and life cycle changes. In this study, we aimed to investigate the effects of blood transfusion on hemodynamic parameters by the Ambulatory Blood Pressure Monitoring method on the day of transfusion in patients with a diagnosis of Beta-Thalassemia Major. Material and Methods: This study was conducted in patients who were followed up with a diagnosis of BTM between June 2020 and July 2020. The study consisted of 30 patients. The blood pressure of the patients was measured by auscultation method on the morning of the day when they received routine red blood cell transfusion treatments, and the patients were fitted with an Ambulatory Blood Pressure Monitoring device. With Ambulatory Blood Pressure Monitoring, mean systolic blood pressure, diastolic blood pressure, heart rate, mean arterial pressure, values were calculated for each patient. Statistical analysis was performed by the IBM SPSS Statistics 21 package program. The significance limit for the p-value was accepted as &lt;0.05. Results: There was a significant difference in mean systolic blood pressure and heart rate values between pre-transfusion, transfusion, and post-transfusion periods. In our study, the rate of white coat hypertension was 8.3%, and the rate of masked hypertension was 4.1%. It was observed that 67% of the patients were non-dippers, and the blood pressure burden of one patient was more than 25%. Conclusions: Measurement of hemodynamic parameters with Ambulatory Blood Pressure Monitoring is the gold standard in terms of detection and follow-up of non-dipper patients, indicating increased cardiovascular risk. In practice, Ambulatory Blood Pressure Monitoring should be used more in the follow-up of chronic patients.