Thalassemia Research Articles

A New Formula Based on Simple Blood Indices to Differentiate Beta Thalassemia Trait from Iron Deficiency Anemia.

Thalassemia is an inherited blood disorder with a defect in the sufficient production of a protein called hemoglobin. We aimed to investigate the simple blood indices of patients with Beta Thalassemia Trait (BTT) and Iron Deficiency Anemia (IDA) to propose a new formula using logistic regression for differentiate two characteristics from each other. Among the 702 records of the BTT Counseling Center (Khoy, Iran-2022), 292 cases (219 iron deficiency anemia (IDA) and 73 BTT) were eligible for the study. Blood indices such as RBC, HGB, HbA2 described and used to diagnose two types of participants. Blood indices had high multicollinearity that was modified. Logistic regression for blood indices fitted and goodness of fit indices with Area Under ROC curve (AUC) estimated. The average age of the participants was 24.56 yr. The status of Multicollinearity between independent variables was modified. The HGB, MCV, HbA2, and HbA variables were used in the model and only HbA2 status was significant (P<0.001). According to the output of the model, for each unit increase in HbA2, the chance of having BTT was about 8.5 times higher than IDA. The sensitivity, specificity, AUC curve, and accuracy of the final model were estimated to be 97, 72, 84, and 93%, respectively. A regression formula to differentiate BTT from IDA proposed. In studies related to the differentiation of the BTT from IDA, the presence of the HbA2 index in the model and prediction is very necessary.

Anti-sickling effect of Vigna subterranean (L.) Verdc on sickle cell beta thalassemia

Sickle cell disease affects millions of people worldwide and has been recognized as a global health concern by WHO. Presently, there is no cure for sickle cell disease. Treatment options which include bone marrow, stem cell transplantation, blood transfusions, and hydroxyurea are not only expensive but have their side effects. Medicinal plants are often employed in the treatment of diseases because of the therapeutic effects of the secondary metabolites in them. Vigna subterranean an important leguminous crop in Africa, is used in some parts of the world for the treatment and management of sickle cell disease. However, there are no established link between the use of Vigna subterranean and their pharmacological effects. The present study investigated the therapeutic effect of Vigna subterranean on a variant of sickle cell disease known as sickle cell beta thalassemia. Parameters such as reversibility test, polymerization test, osmotic fragility test, deoxygenation test, beta synthesis and oxy-haemoglobin concentration were used to study the anti-sickling potentials of sickle cell beta thalassemia. The result showed that the plant extract reversed the sickled cells, reduced the rate of polymerization, maintained the stability of the cell membrane, increased beta globin synthesis and increased the oxy-haemoglobin concentration. This suggests that Vigna subterranean possesses anti-sicking properties and could be used as an effective therapeutic for the treatment and management of sickle cell beta thalassemia.

Alpha globin gene alterations modifying the phenotype of homozygous beta thalassaemia.

The phenotype of β-thalassemia varies widely. The primary determinant is the type of beta-globin gene mutation; however, there are secondary and tertiary modifiers also as associated alpha mutations, polymorphisms, as well as coinheritance of mutations affecting other related systems. Co-inheritance of alpha thalassemia mutations is known to ameliorate the severity of HbE-β thalassemia. However, the role of alpha globin gene alterations (deletions and triplication) is not well illustrated in homozygous β-thalassemia. Here we evaluated the role of alpha globin gene alterations in 122 β-thalassemia patients having IVS1-5 (G>C) homozygous mutation. β-thalassemia mutations were detected by ARMS PCR and alpha mutations by GAP-PCR. Gene expression by qRT-PCR. Out of 122 cases, 15 patients had alpha 3.7 triplications (ααα3.7anti), 24 had alpha 3.7kb deletion (-α3.7) mutation and three patients had 4.2kb deletion (-α4.2). Patients were divided into two groups, requiring less than 8 units (NTDT) and more than 8 units (TDT) of blood transfusion per year (≥8U BT/year). The percentage of alpha deletion was significantly (p=0.0042) high in NTDT (42.1%) as compared with TDT (13.2%). Conversely, the proportion of alpha triplication is high in the TDT as compared with NTDT. Even mean serum ferritin level was found to be significantly high in patients having alpha triplication as compared with those having alpha deletions (p=0.0184) and normal alpha gene (p=0.0003). α/β globin ratio was highest in TDT patients with alpha triplication and lowest in NTDT patients with alpha-del. The results show that concurrent inheritance of alpha gene alterations influences the phenotypic severity of homozygous β-thalassemia.

Revolutionizing Anemia Classification with Multilayer Extremely Randomized Tree Learning Machine for Unprecedented Accuracy

Anemia is a prevalent global health issue that is characterized by a deficit in red blood cells or low levels of hemoglobin. This condition is influenced by various causes, including nutritional inadequacies, chronic diseases, and genetic predisposition. The incidence of the phenomenon exhibits variation across different geographical regions and demographic groups. This pioneering research investigates the identification and classification of anemia, potentially leading to transformative advancements in the discipline. The classification of anemia encompasses four distinct groups, namely Beta Thalassemia Trait, Iron Deficiency Anemia, Hemoglobin E, and Combination. This comprehensive categorization offers clinicians a more refined and detailed comprehension of the condition. The integration of deep learning and machine learning in the Multilayer Extremely Randomized Tree Learning Machine (MERTLM) model represents a departure from traditional approaches and a significant advancement in the field of medical categorization accuracy. The MERTLM approach integrates randomized tree with multilayer extreme learning machine (M-ELM) representation learning, hence emphasizing the possibility of interdisciplinary collaboration in the field of diagnostics. In addition to its impact on anemia, artificial intelligence (AI) is playing a significant role in revolutionizing medical diagnosis by emphasizing the integration of innovative methods. This study utilizes the combined capabilities of machine learning and deep learning to improve accuracy. Notably, recent developments have resulted in an exceptional accuracy rate of 99.67%, precision of 99.60%, sensitivity of 99.47%, and an amazing F1-Score of 99.53%. This study represents a significant advancement in the field of anemia research, providing valuable insights that may be applied to intricate medical issues and enhancing the quality of patient care.

Evaluation of iron overload in visceral organs in thalassemia patients by point shear-wave elastography.

The aim of this study was to investigate the value of point shear-wave elastography (pSWE) in the measurement of iron overload in the liver and other visceral organs in patients with beta thalassemia major (BTM). The study included 103 patients diagnosed with BTM who were referred to our clinic for cardiac and liver T2* measurement and a control group of 120 age- and gender-matched healthy volunteers. Cardiac and hepatic T2* measurements were performed in the patient group. Hepatic, pancreatic, splenic, and renal pSWE values were measured in both groups. The pSWE values were compared between the two groups. In the patient group, correlations between pSWE values, cardiac-hepatic T2* values and hepatic size, patient age, and serum ferritin levels were analyzed. Hepatic, pancreatic, splenic, and renal pSWE values were significantly higher in the patient group compared to the control group (p ≤ 0.001, < 0.001, 0.014, 0.026, respectively). In the patient group, hepatic pSWE values established a significant correlation with cardiac T2* values, liver size-T2*, pancreatic pSWE values, serum ferritin levels, and age (p = 0.006, < 0.001, 0.001, 0.042, 0.001, 0.032, respectively). In the ROC analysis, the area under the ROC curve was 0.807 for hepatic pSWE in the discrimination of thalassemia patients and healthy controls, and the cut-off value was 1.42, which gave a sensitivity and specificity of 75.7% and 75%, respectively. CONCLUSıON: Point shear-wave elastography can be a useful technique in the clinical measurement of iron overload in the liver, pancreas, spleen, and kidney.

The relationship between liver stiffness by two-dimensional shear wave elastography and iron overload status in transfusion-dependent patients

Increased liver stiffness (LS) can be result of increased liver iron concentration (LIC) which may not yet be reflected in the liver fibrotic status. The objective of our study was to examine relationship between hemochromatosis, LS, and serum ferritin level in transfusion-dependent patients. We recruited all 70 transfusion-dependent patients, whose median age was 15, referred for evaluating LIC status by magnetic resonance imaging (MRI) followed by two-dimensional ultrasonography shear wave elastography (2D-SWE). Thalassemia beta affected the majority of the patients. The optimal cut point for prediction of severe hemochromatosis using median SWE (kPa) and SWV (m/s) was ≥ 7.0 kPa and ≥ 1.54 m/s, respectively, with sensitivity of 0.76 (95% confidence interval [CI] 0.55, 0.91) and, specificity of 0.69 (95%CI 0.53, 0.82). When combing the optimal cut point of SWE (kPa) at ≥ 7.0 and serum ferritin ≥ 4123 ng/mL, the sensitivity increased to 0.84 (95%CI 0.64, 0.95) with specificity of 0.67 (95%CI 0.50, 0.80), positive predictive value (PPV) of 0.60 (95%CI 0.42, 0.76), and negative predictive value (NPV) of 0.88 (95%CI 0.71, 0.96). Simultaneous tests of 2D-SWE and serum ferritin for prediction of severe hemochromatosis showed the highest sensitivity of 84% (95%CI 0.64–0.95), as compared to 2D-SWE alone at 76% (95%CI 0.55, 0.91) or serum ferritin alone at 44% (95%CI 0.24–0.65). We recommend measuring both 2D-SWE and serum ferritin in short interval follow up patients. Adding 2D-SWE to management guideline will help in deciding for aggressive adjustment of iron chelating medication and increased awareness of patients having severe hemochromatosis.

In brief: Casgevy for beta thalassemia.

Exagamglogene autotemcel (Casgevy – Vertex), a cell-based gene therapy recently approved for treatment of sickle cell disease1, has now been approved by the FDA for treatment of patients ≥12 years old with transfusion-dependent beta thalassemia.

Guideline for the management of conception and pregnancy in thalassaemia syndromes: A British Society for Haematology Guideline.

This comprehensive guideline, developed by a representative group of UK-based medical experts specialising in haemoglobinopathies, addresses the management of conception and pregnancy in patients with thalassaemia. A systematic search of PubMed and EMBASE using specific keywords, formed the basis of the literature review. Key terms included "thalassaemia," "pregnancy," "Cooley's anaemia," "Mediterranean anaemia," and others, covering aspects such as fertility, iron burden and ultrasonography. The guideline underwent rigorous review by prominent organisations, including the Endocrine Society, the Royal College of Obstetricians and Gynaecologists (RCOG), the United Kingdom Thalassaemia Society and the British Society of Haematology (BSH) guideline writing group. Additional feedback was solicited from a sounding board of UK haematologists, ensuring a thorough and collaborative approach. The objective of the guideline is to equip healthcare professionals with precise recommendations for managing conception and pregnancy in patients with thalassaemia.

Beta thalassemia major, hypogonadism and cardiovascular risk

Beta thalassemia major, hypogonadism and cardiovascular risk

Evaluation of anti-sickling effects of two varieties of Cajanus cajan (L.) Huth on sickle cell beta thalassemia

Ethno-pharmacological relevance: Globally, the prevalence of sickle cell disease is on the rise, with developing countries experiencing particularly alarming mortality rate compared to developed nations. The World Health Organization (WHO) and United Nations (UN) have acknowledged sickle cell disease as a significant global public health concern. Unfortunately, a cure for this condition is yet to be discovered, and existing allopathic treatments, while offering relief, come with serious side effects. In recent times, there has been a growing interest in exploring the potential of medicinal plants for treating sickle cell disease due to their content of secondary metabolites that may impact the disease's mechanisms. Cajanus cajan, a crucial grain legume in rain-fed agriculture in semi-arid tropics, has been traditionally used in folk medicine to manage various illnesses and is suggested to possess anti-sickling properties.Aim of the study: The present study investigated two varieties of C. cajan for their effectiveness in treating sickle cell beta thalassemia, a variant of sickle cell disease. Materials and methodsThe study was divided into four groups consisting of the untreated group (group 1), group treated with standard drug (group 2), group treated with white C. cajan (group 3) and group treated with brown C. cajan (group 4). The effects of the two variety of C. cajan were measured by polymerization test, reversibility test, osmotic fragility test, deoxygenation and beta globin synthesis test. ResultThe results revealed that both varieties of C. cajan demonstrated a reduction in polymerization rates, reversed sickled red blood cells, increased the oxygen affinity of Hb-S/β, elevated the Fe2+/Fe3+ ratio, and maintained the membrane stability of red blood cells. Notably, the white variety exhibited superior anti-sickling properties compared to the brown variety. ConclusionThis suggests that this significant leguminous crop could be utilized for the treatment and management of sickling disorders, particularly in low-income countries where conventional treatments may be financially inaccessible to patients.

“The Parental Perspective of Thalassemia in Bangladesh: Challenges for Prevention and Management of Thalassemia”

Introduction: Thalassemia is a genetic blood disorder characterized by abnormal hemoglobin production, poses significant challenges for families worldwide. In Bangladesh, where the prevalence of thalassemia is notable, parents face unique hurdles in both preventing and managing this condition. Aim of the study: The aim of this study is to explore the parental perspective of thalassemia in Bangladesh, focusing on the challenges faced in the prevention and management of the disease. Methods: This was a cross section retrospective study conducted in the Department of Paediatrics of M Abdur Rahim Medical College, Dinajpur, Bangladesh during the period from June 2023 to December 2023. Result: Among the total of 320 caregivers, 46.9% were father, while 53.1% were mother respectively. Minority 14.1% of marriages were consanguineous, while the majority (85.9%) was not. The majority (82.8%) of respondents had one thalassemic child, while 17.2% had two or more thalassemic children. Before the diagnosis of thalassemia in their child, 90.9% of respondents had not heard about thalassemia. All respondents (100%) reported not undergoing thalassemia screening before marriage. The median age at diagnosis of thalassemia among the participants was 1.32 years. Beta thalassemia was diagnosed in 30.6% of the participants, while 68.8% had E-beta thalassemia. The majority 65.9% of respondents correctly identified thalassemia as a genetic disease, while 22.5% provided an incorrect response. Conclusion: Thalassemia presents significant challenges for affected individuals and their families in Bangladesh, ranging from limited access to diagnostic services and blood transfusions to social stigma and financial burdens.

Caregivers' Burden and Mental Health of the Caregivers of β-Major Thalassemia Patients: Mediating Role of Religious Coping

Background: Caregiver burden among those caring for patients with thalassemia major in Pakistan poses significant psychological challenges. The role of religious coping mechanisms in alleviating psychological distress and enhancing well-being among caregivers has been highlighted in prior research, suggesting a complex interplay between caregiver strain, coping strategies, and mental health outcomes. Objective: This study aims to investigate the relationships between caregiver burden, positive religious coping, and mental health outcomes, specifically psychological well-being and distress, among caregivers of thalassemia patients in the Twin cities of Islamabad and Rawalpindi. Methods: Employing a cross-sectional design, the study included 180 caregivers of thalassemia patients, recruited through non-probability purposive sampling from major thalassemia centers and hospitals in Islamabad and Rawalpindi. Data were collected using the Zarit Caregiver’s Burden Scale, the Brief Religious Coping Scale, and the Mental Health Inventory. Structural Equation Modeling (SEM) was utilized to analyze the data, using SPSS and AMOS software, with a focus on the mediating role of positive religious coping between caregiver burden and mental health outcomes. Results: The analysis revealed that caregiver burden significantly predicted the use of positive religious coping (β = .32, p &lt; .001) and was negatively associated with psychological well-being (β = -.33, p &lt; .001) while positively associated with psychological distress (β = .23, p &lt; .01). Positive religious coping positively influenced psychological well-being (β = .28, p &lt; .01) and negatively influenced psychological distress (β = -.21, p &lt; .05). The model explained 38.2% of the variance in psychological well-being and 34.1% in psychological distress. Conclusion: The findings underscore the significant impact of caregiver burden on the mental health of caregivers, with positive religious coping serving as a beneficial mediating factor. Enhancing positive religious coping among caregivers may be a viable intervention strategy to improve their mental health outcomes.

®-Thalassemia intermedia: implication of presenting 〈-globin gene triplication

®-Thalassemia intermedia: implication of presenting 〈-globin gene triplication

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

Accidental finding of beta thalassemia minor in a patient during a glycosylated hemoglobin rutinary assay

Accidental finding of beta thalassemia minor in a patient during a glycosylated hemoglobin rutinary assay

Influence of iron deficiency anemia on hemoglobin A2 Levels: Possible consequences for beta thalassemia screening

Influence of iron deficiency anemia on hemoglobin A2 Levels: Possible consequences for beta thalassemia screening

Multiparametric cardiac magnetic resonance in patients with thalassemia intermedia: new insights from the E-MIOT network.

In a relatively large cohort of thalassemia intermedia (TI) patients, we systematically investigated myocardial iron overload (MIO), function, and replacement fibrosis using cardiac magnetic resonance (CMR), we assessed the clinical determinants of global heart T2* values, and we explored the association between multiparametric CMR findings and cardiac complications. We considered 254 beta-TI patients (43.14 ± 13.69years, 138 females) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia project. MIO was quantified by T2* technique and biventricular function and atrial areas by cine images. Macroscopic myocardial fibrosis was detected by late gadolinium enhancement technique. Compared to never/sporadically transfused patients, regularly transfused (RT)-TI patients exhibited significantly lower global heart T2* values, biventricular end-diastolic volume indexes, left ventricular mass index, and cardiac index. In RT-TI patients, age and serum ferritin levels were the strongest predictors of global heart T2* values. Independently from the transfusional state, cardiac T2* values were not associated with biventricular function. Of the 103 (40.6%) patients in whom the contrast medium was administrated, 27 (26.2%) had replacement myocardial fibrosis. Age, sex distribution, cardiac iron, and biventricular function parameters were comparable between patients without and without replacement myocardial fibrosis. Twenty-five (9.8%) patients had a history of cardiac complications (heart failure and arrhythmias). Increased age and replacement myocardial fibrosis emerged as significant risk markers for cardiac complications. In TI, regular transfusions are associated with less pronounced cardiac remodeling but increase the risk of MIO. Replacement myocardial fibrosis is a frequent finding associated with cardiac complications.

Red Cell Parameters in Beta Thalassemia Trait; Comparison between Iron Deficient and Non-Deficient Carriers

Objective: To compare hematological parameters in iron-deficient and non-deficient carriers of beta thalassemia trait. Study Design And Setting: Comparative cross-sectional study. This study was conducted at the Department of Hematology at PNS SHIFA Hospital, Karachi for six months (February 2023 to July 2023). Methodology: This comparative cross-sectional study included a total of 304 cases with beta thalassemia trait and was divided into two groups; the Iron-deficient (ID+) and iron-deficient (ID-) group. The study focused on red cell parameters i.e, Hemoglobin (Hb), TRBC, MCV, MCH and RDW. Haemoglobin Electrophoresis results of both groups were also compared. Descriptive statistics were expressed as mean ± SD and the Chi-square test was assigned. A p-value = 0.05 was considered statistically significant. Results: Out of the total 304 subjects, 76 (25.0%) had iron deficiency, and 228 (75.0) had sufficient iron stores. Mean age of patients was 18 (Range: 3 – 35) years. HbA levels were similar in both the groups with p-value &gt; 0.05. While all other parameters compared showed marked differences among the two groups and were found to be statistically significant. Hb, TRBC, MCV MCH showed lower values in the ID+ group while RDW was lower in the ID- group. Conclusion: Red Cell parameters and HBA2 levels in beta thalassemia trait vary significantly among the iron deficient vs non-deficient group. Hence due consideration is needed in screening of beta thalassemia trait in patients with iron deficiency anemia.

Diagnosing delta-beta thalassaemia in a resource poor setting

An eight-year-old girl presented with mild scleral icterus, pallor and hepatosplenomegaly. Her preliminary investigations revealed low haemo-globin (Hb) (94g/L), high reticulocyte count (3.5%), normal total bilirubin level and normal liver function tests. Her blood picture revealed evidence of chronic haemolysis. High perfor-mance liquid chromatography (HPLC) revealed markedly raised Hb-F (98.3%). Capillary electro-phoresis revealed Hb-F of 99.2%. Acid elution test (Kleihauer test) showed pan-cellular distribution of Hb-F. Her parents were first cousins. Her mother’s profile showed thalassaemic red cell indices with normal Hb-A2 and high Hb-F (13.3%). The father was not available for screening. The paternal grandmother’s HPLC showed normal Hb-A2 and high Hb-F (6.8%). Based on clinical and laboratory findings and family screening results, the child was diagnosed as homozygous delta-beta (αβ)-thalassaemia presenting as thalassaemia intermedia.

Genotype and Phenotype in Pregnant Women with Both Alpha and Beta Thalassemia Mutations Attended at Vietnam National Hospital of Obstetrics and Gynecology

Introduction: The number of studies that explore people with both alpha and beta thalassemia mutations is still low, not only in Vietnam but around the world as well. We conducted this study to explore genotypes and phenotypes of pregnant women who have both alpha and beta thalassemia mutations in comparison to those who don’t have any thalassemia mutations and those who have either alpha or beta thalassemia mutations. Methods: This was a cross-sectional study conducted in the National Hospital of Obstetrics and Gynecology from September 2020 to July 2021 on medical records of 6929 pregnant women who attended the hospital between 2015 and 2021. Mutation analysis was performed by the α-Globin Strip Assay (Vienna Lab, Austria) and Strip Assay MED (Vienna Lab, Austria). Results: There were 18 pregnant women with both alpha and beta thalassemia genes, in which only SEA mutation caused alpha thalassemia and nearly 70% of beta thalassemia was caused by CD26 mutation. In comparison with pregnant women who didn’t have any thalassemia genes, those with both mutations had higher RBC, RDW, HbA2 and lower HGB, HCT, MCV, MCH, MCHC, and HbA1. We only see the statistically significant difference in HbA1 and HbA2 between those with both mutations and those with either alpha or beta thalassemia mutations. Conclusion: In conclusion, our study showed that there were differences in genotype and phenotype between pregnant women with both alpha and beta thalassemia mutations and other types of thalassemia as well as those without thalassemia.