Search Results (262)

Introduction: Generally, microcytic anaemia is caused by sideropenia or a genetic gap. The suspicion that microcytic anaemia is caused by a genetic gap must always be considered in the face of an inadequate response to martial therapy. The aim of this paper is to highlight how biochemical diagnosis alone is sometimes not sufficient to understand the cause of microcytic anaemia. For this reason, for a correct genotype–phenotype correlation, it is essential to identify the defective gene underlying the microcytic anaemia. Detailed Case Description: This case concerns a married couple who both have microcytic anaemia. They came to our attention because the lady, pregnant at 12 weeks, underwent screening for chromosomal abnormalities using combined tests in the first trimester of pregnancy. A biochemical screening performed ten years earlier showed that both spouses were healthy carriers of the beta-thalassemia trait. A careful analysis of the biochemical data and an in-depth molecular diagnosis of the alpha and beta globin genes showed that the woman was a healthy carrier of the beta-thalassemia trait while the husband was a healthy carrier of a mutation in the ALAS2 gene. Analysis of the biochemical data of her husband and family members revealed that she had X-linked microcytic sideroblastic anaemia caused by an alteration in the function of the ALAS2 (5′-Aminolevulinate Synthase 2) gene located on the short arm of the X chromosome (Xp11.21). Discussion and Conclusions: This result is very relevant as, during genetic counselling, we explained to the couple that invasive prenatal diagnosis was not necessary as there is no risk of procreating a transfusion-dependent individual. Full article

Background: Thalassemias are a group of autosomal recessive disorders and the most common inherited disease worldwide. Fetal hemoglobin (HbF) is the main oxygen carrier protein in the human fetus. Elevated HbF level is known to ameliorate the severity of HbE/β and β-thalassemia. This study aimed to investigate whether two commonly known HbF-associated SNPs (rs28384513 and rs4895441) in the HBS1L-MYB region are associated with HbF level and disease severity in Bangladeshi HbE/β-thalassemia patients. Methods: Blood samples were collected from 160 participants (120 HbE/β-thalassemia patients and 40 healthy controls). Hematological analysis was performed using complete blood count (CBC) and capillary Hb electrophoresis. After genomic DNA extraction, real-time PCR-based high-resolution melting (HRM) for SNP detection, targeting the HBS1L-MYB intergenic region, was done. Results: Patients carrying rs28384513 and rs4895441 SNPs had significantly higher HbF (1.29 ± 1.63 and 1.49 ± 1.7 g/dL, respectively) compared to major allele ‘TT’ and ‘AA’ (0.87 ± 1.1 and 1.19 ± 1.65 g/dL, respectively) with a p-value of 0.01 and 0.03, respectively. It has been detected that HbF levels in SNP-carrying patients significantly correlated with the higher transfusion interval (60 days, r = 0.38, p < 0.0001) and age of first transfusion (65 months, r = 0.26, p < 0.0028) in these patients. Further, non-transfusion-dependent patients had the highest HbF level (2.03 ± 2.05 g/dL) compared to transfusion-dependent moderate (0.58 ± 0.78 g/dL) and severe (0.84 ± 1.27 g/dL) patients generating a significant p-value < 0.0001 in One-Way ANOVA test. The minor allele frequencies of rs28384513 (G) and rs4895441 (G) were found to be 0.43 and 0.11 respectively. Conclusion: These findings suggest that SNPs of HBS1L-MYB may have a role in elevated HbF levels and ameliorating disease severity in terms of transfusion in HbE/β-thalassemia patients. Full article

Thalassemia represents a diverse group of inherited hematological disorders characterized by defective globin chain synthesis, leading to chronic anemia and associated complications. The complicated pathophysiology of beta-thalassemia involves genetic mutations or rarely deletions of the beta-globin gene on chromosome 11 whereas alpha-thalassemia involves deletions in the HBA1 and HBA2 genes or occasionally alterations to the DNA sequence in or around these genes. These mutation and deletion effects disrupt the balance of α/β-globin chain production, resulting in ineffective erythropoiesis, hemolysis, and a cascade of clinical manifestations including anemia, bone deformities, and iron overload. Advances in diagnostic techniques have enhanced our ability to detect and characterize these mutations, facilitating early and accurate diagnoses. Current management strategies encompass regular blood transfusions, the use of hydroxyurea to improve hemoglobin levels, and iron chelation therapy to prevent iron-related organ damage. Moreover, other therapeutics such as thalidomide for those not responding to hydroxyurea, Sirolimus for patients with immunodeficiencies, and use of vitamin E as an antioxidant have proven to be effective. Innovative therapies such as gene therapy and bone marrow transplantation offer promising curative potential, opening a new era in the treatment of thalassemia. This review focuses on pathophysiological mechanisms underlying thalassemia, explores the diagnostic methodologies, and highlights recent advancements in therapeutic approaches. Full article

HbF induction is an appropriate strategy to ameliorate the severity of β-thalassemia symptoms. Hydroxyurea (HU) is the most common chemical agent introduced as an HbF inducer but responsiveness to HU is variable and the introduction of HbF inducers alternative to HU with low cytotoxicity has been a crucial challenge. Resveratrol is an HbF inducer agent that may have favorable effects on the differentiation of hematopoietic erythroid progenitors (HEPs). The present study aimed to investigate the effect of resveratrol on γ-globin, stress response, and anti-apoptotic gene expression among hydroxyurea (HU)-responders and HU-nonresponders (HU-NR). Four cases of HU-R and four cases of HU-NR were studied. HEPs of the patients were cultured, and the expression of γ-globin, Foxo3, and Bclxl was assessed. Moreover, the differentiation and apoptotic rate of the cells were investigated using flow cytometry analysis. In three cases, the γ-globin gene expression increased after resveratrol treatment. All of the HU-NR patients were also non-responders to resveratrol (Res-NR). The expression of Foxo3 and Bclxl genes was higher in responders to resveratrol (Res-R) compared to non-responders (Res-NR). The rate of apoptosis in Res-R patients was also lower than in Res-NR. Responders to resveratrol also had a higher rate of HEP maturation. The cells of both HU–NR and Res-NR patients could not adapt to stress conditions and proceed to the erythroid differentiation. In conclusion, resveratrol increased the γ-globin expression in HEPs of β-thalassemia patients. The response was observed only in R-HU patients with similar cellular pathways. Full article

Background: The effective management of iron overload in transfusion-dependent thalassemia (TDT) requires adherence to iron chelation therapy (ICT). However, adherence rates among pediatric thalassemia patients remain suboptimal. This study aimed to evaluate adherence levels and identify sociodemographic and clinical factors impacting ICT adherence in pediatric TDT patients from Sarbaz-Rask, Iran. Methods: This cross-sectional study assessed 58 pediatric TDT patients aged 2–18 years at a thalassemia clinic from April 2021 to March 2022. Adherence was evaluated using the medication possession ratio. Logistic regression and correlation analyses identified predictors of adherence and treatment efficacy based on serum ferritin levels. Results: Adherence was satisfactory in 58.6% of patients and associated with younger maternal age (93.8% for 18–30 years, p = 0.008) and urban residency (p = 0.02). Logistic regression identified urban residency (OR = 20.265, p = 0.073) and a maternal age of 18–30 years (OR = 39.236, p = 0.005) as key predictors of adherence. Adherence was not significantly influenced by having a sibling with thalassemia or the maternal educational level. Treatment efficacy was observed in 27.6% of patients. Maternal age impacted adherence in poorly controlled patients (p = 0.007). Urban residents showed higher adherence rates, particularly with poor control (p = 0.017). Conclusions: Younger maternal age and urban residency emerged as positive predictors of adherence and treatment efficacy in pediatric thalassemia patients from Sarbaz-Rask. Targeted interventions supporting rural families and those with older maternal caregivers may improve adherence and outcomes in this population. Full article

β-thalassemia, a life-threatening inheritable hemoglobin disorder caused by mutations in the HBB gene, poses a significant public health challenge in the world. Although no comprehensive work has been carried out in Bangladesh, the world prevalence and small-scale works indicated the possibility of a high prevalence of this disease in the country. Therefore, this review aims to explore the present situation of β-thalassemia in Bangladesh and propose approaches to mitigate its impact in the future. Limited awareness, a high incidence of consanguineous marriage, and inadequate access to healthcare are possible factors responsible for the high prevalence of thalassemia in Bangladesh, while the absence of public health policy and a national health insurance system further exacerbate the situation. The understanding of the genetic landscape and modern treatment strategies for β-thalassemia is hindered by the lack of comprehensive data on the mutation spectrum. In addition to conventional therapy such as blood transfusion, advanced practices such as splenectomy, hematopoietic stem cell transplantation, and emerging therapies such as gene therapy show promise for future cures but have yet to be widely implemented in this country. To effectively address the challenges of β-thalassemia, it is crucial to adopt comprehensive strategies, including a public awareness campaign, public health intervention, mandatory premarital screening, genetic counselling, and a national thalassemia prevention program. Additionally, understanding the spectrum of mutations and new therapeutic interventions is crucial for advanced healthcare strategies. Full article

The mutation HBA2:c.*94A>G (AATAAA>AATAAG; rs63751269) is a 3′-UTR (3 prime untranslated region) single-nucleotide substitution in the polyadenylation (PA) signal of HBA2 (α^PA:A→G). This pathogenic (CADD score, 14.92) variant is sporadic in the Arabian Peninsula. It results in inefficient mRNA processing, transcription termination, and possibly using an alternate cryptic downstream polyadenylation signal. As a result, the allele α^T (or α^T-Saudi) poses challenges in premarital counseling with respect to fetal risk of hemoglobin H disease. Homozygous HBA2:c.*94A>G (α^Tα/α^Tα) results in moderate-to-severe microcytosis (mean red cell volume, MCV, 55 to 65 fL), reflecting markedly impaired hemoglobin synthesis (hemoglobin H disease). Homozygous rightward −α^3.7 (a 3804-neocleotide deletion allele, NM_000517.4:c.[-2_-3delAC; −α^3.7]), on the other hand, results in mild microcytosis (MCV, 70 to 75 fL, alpha-thalassemia trait). Thus, HBA2:c.*94A>G is more damaging than −α^3.7. Consistently, the value of MCV in compound heterozygosity, HBA2:c.*94A>G and −α^3.7, is 65 to 70 fL. We report here a healthy couple who presented for premarital counseling on their hemoglobinopathy. The man has homozygous HBA2:c.*94A>G (α^Tα/α^Tα), and the woman has compound heterozygous (−α^3.7/α^Tα, also annotated as: ^−3.7α/α^Tα). As a result, the genotype of their offspring would be that of the father (α^Tα/α^Tα) or the mother (−α^3.7/α^Tα). The counseling was mainly based on the benign phenotypes of the parents. As both were asymptomatic and their anemia was clinically insignificant, they proceeded with the marriage. Full article

Thalassemia a common hereditary blood disorder resulting in anemia. It is an important public health problem, with a high prevalence in Southeast Asia and Mediterranean countries, and preventable through screening programs. However, due to its chronic nature, permanent physical changes, troublesome complications, and lifelong treatment, pediatric patients with thalassemia major are more prone to mental disorders and cognitive impairment. Internalizing and externalizing problems are higher in pediatric patients with thalassemia. Children with β-thalassemia major exhibit lower IQ scores than healthy children. Neurophysiology and neuroimaging examinations have shown abnormal results in children with thalassemia. Co-morbidity with mental disorders increases the mortality, morbidity, and total healthcare costs of patients with thalassemia. Therefore, routine evaluation of mental health problems is recommended to accommodate the early detection and prompt treatment of mental disorders. A multidisciplinary approach for thalassemia patients and families should be delivered by providing appropriate medical care, psychosocial support, and good transition care to improve survival and well-being, assist good social integration and daily functioning, and cope with the stress of chronic disease. Full article

Extramedullary hematopoiesis (EMH) serves as a compensatory mechanism in chronic hemolytic anemias, such as thalassemia, and can result in spinal cord compression. This case report highlights a 36-year-old woman with transfusion-dependent β-thalassemia (TDT) who presented with lower extremity motor deficiency, pelvic paresthesia, and bladder dysfunction. The patient had a history of lower back pain, bilateral lower limb weakness, and demonstrated poor compliance with iron chelation therapy. MRI findings indicated spinal cord compression attributable to extramedullary hematopoiesis. Due to the infeasibility of surgical intervention, the patient underwent hypertransfusion and iron chelation therapy. While neurological symptoms improved, urinary retention persisted. The patient continues to receive iron chelation treatment and undergo transfusions. Managing extramedullary hematopoiesis in thalassemia necessitates an individualized treatment approach. Full article

In patients with sickle cell disease (SCD), transfusions pose risks like delayed hemolytic transfusion reaction (DHTR) and hyperhemolytic syndrome (HHS). We present the case of a 61-year-old Nigerian male patient with SCD, developing hyperhemolytic syndrome (HHS) post-orthopedic surgery due to alloimmunization from blood transfusions. Surgery induced massive hemorrhage, requiring RBC transfusions. Postoperatively, he developed HHS with jaundice, hemoglobinuria, and fever. Despite additional transfusions, his condition worsened, leading to hematological consultation on postoperative day +9. Laboratory findings showed positive DAT and multiple alloantibodies. The diagnosis of HHS was established and treatment involved high-dose methylprednisolone, intravenous immunoglobulin (IVIG), and erythropoietin. The patient was discharged on postoperative day +24 with stable hemoglobin levels, tapering doses of methylprednisolone, and continuous administration of hydroxyurea prescribed. HHS pathogenesis involves extensive intravascular hemolysis, exacerbated by alloimmunization. Diagnostic challenges and therapy selection complexity underscore the need for cautious transfusion strategies in HHS, reserving them for hemodynamic instability or hypoxia. This case highlights promptly recognizing and managing HHS in SCD for improved outcomes and avoiding unnecessary transfusions. Full article

Thalassemia is a hereditary hemolytic anemia that is prevalent in Southeast Asia. The primary treatment for severe thalassemia involves red cell transfusion, iron chelation, and the treatment of long-term complications, leading to frequent hospital visits and admissions. This study aims to delineate the causes and characteristics of hospital admissions among thalassemia patients under the National Health Coverage (NHC) scheme in Thailand. This cross-sectional analysis (2015–2019), conducted using the National Health Security Office database, identified 336,054 admissions among 41,237 patients, with alpha-thalassemia at 12.5%, beta-thalassemia at 61.5%, other thalassemia at 0.5%, and unclassified thalassemia at 25.5%. The overall admission rate was 3.74 per 100 NHC admissions in the pediatric age group. Infections predominated in younger patients, whereas cardiac complications, diabetes mellitus, and cholecystitis/cholelithiasis were more common in older patients. Hospital admissions for cardiac complications and diabetes mellitus in pediatric patients with thalassemia decreased over the study period. The annual hospital admission cost ranged from 8.19 to 12.01 million US dollars, with one-third attributed to iron chelation. In summary, thalassemia poses a significant healthcare challenge in Thai children, characterized by high admission rates and costs. While infections predominate in younger patients, cardiac complications and diabetes mellitus are more common in older individuals. The diminishing admissions for these complications suggest the successful implementation of iron chelation medications. Full article

Thalassemia treatment still relies on supportive care, mainly including blood transfusion and iron chelation therapy. Iron chelation is considered the main factor responsible for the marked improvement in survival rates of thalassemic patients. Hemosiderosis may be prevented if appropriate chelation therapy is offered from early childhood, with timely dose adjustments according to changing body weight and close monitoring of organ iron load. With three iron chelators currently available, the choice of appropriate chelation, either as monotherapy or combined therapy, should be individualized depending on the iron overload of target organs, patient’s age, presence of adverse events and compliance issues, given known limitations related to each agent’s administration. Full article

Indonesia is a large island country with a wide variety of ethnic groups. As part of the thalassemia country belt, Indonesia has alleles that are as distinctive as those found in other parts of Southeast Asia. The journey of ancestors in the prehistoric period and the massive increase in human exchange in the last decade have formed the current population of Indonesia. The mutants of the beta-thalassemia allele brought by those predecessors can be seen from the traces of their journey. This paperdescribes the flow gene according to the type of mutations of beta-thalassemia in the country. Full article

Background and aim: We conducted a review to determine the efficacy of amlodipine alongside iron chelators on serum ferritin levels and liver T2-weighted magnetic resonance imaging (MRI T2*) in β-thalassemia patients. Methods: Systematic search was conducted in multiple databases, including Web of Science, PubMed, Scopus, Embase, Cochrane Library, ClinicalTrials.gov, the Iranian Registry of Clinical Trials (IRCT), ProQuest, OpenGrey, and Web of Science Conference Proceedings Citation Index. The search was closed in January 2023. Primary outcomes were comprised of liver MRI T2* (millisecond (msec)) and serum ferritin levels (ng/mL). Results: Seven studies (n = 227) were included in the study. The pooled Cohen’s d for serum ferritin was estimated at −0.46, 95% confidence interval (CI) −1.11 to 0.19 and p = 0.16 (I² 86.23%, p < 0.0001). The pooled mean difference for serum ferritin was −366.44 ng/mL, 95% CI −844.94 to 112.05, and p = 0.13 (I² 81.63%, p < 0.0001). After a meta-regression based on the length of using amlodipine, a coefficient for the mean difference was also −23.23 ng/mL and 95% CI −155.21 to 108.75. The coefficient obtained from a meta-regression as per the amlodipine dose at 5 mg/day than 2.5 to 5 mg/day anchored at −323.49 ng/mL and 95% CI −826.14 to 1473.12. A meta-regression according to the baseline values of serum ferritin discovered a coefficient of 1.25 ng/mL and 95% CI 0.15 to 2.35. Based on two included studies (n = 96), the overall Cohen’s d for liver MRI T2* was 2.069, 95% CI −0.896 to 5.035, and p = 0.17 (I² 96.31%, p< 0.0001). The synthesized mean difference for liver MRI T2* was 8.76 msec, 95% CI −4.16 to 21.67, and p = 0.18 (I² 98.38%, p < 0.000). Conclusion: At a very low level of evidence, probably using amlodipine at a dose of 2.5 to 5 mg a day, up to a year, alongside iron chelators slightly decreases serum ferritin levels in iron-overloaded thalassemia cases by nearly 366 ng/mL (23 ng/mL per month). The liver MRI T2* might also rise to 8.76 msec upon co-therapy with amlodipine. Full article

β-thalassemia is a genetic disorder affecting chromosome 16, inherited from one or both parents. In spite of the improved treatment of the hematological disorder and its complications, β-thalassemic patients still exhibit an imbalance in bone mineral turnover, resulting in diminished bone mineral density (BMD), more evident in the lumbar spine. The purpose of this study was to investigate the association between genetic polymorphism of the PPAR-γ gene and the presence of osteopenia or osteoporosis in children with β-thalassemia. This case–control study was conducted on 50 children with β-thalassemia from the pediatric hematology unit of Beni-Suef University Hospital, including 50 healthy children as the control group. The age range was 8 to 18 years. Samples of patients and control subjects were analyzed for the presence of polymorphisms of the PPAR-γ gene and other blood labs. An assay of BMD measure using dual-energy X-ray absorptiometry (DXA) was performed to investigate osteopenia or osteoporosis. Statistical analysis was used to investigate the relationship between the risk of osteopenia or osteoporosis and the presence of PPAR-γ Pro12Ala gene polymorphism. Eighteen (eleven males and seven females) of fifty patients (representing 36% of the patients group) have osteopenia with low bone mineral density (Z-score is −1 or less than 1). There was no statistically significant difference between BMD measurements in males and females. By comparing the frequency of 12 Ala gene polymorphisms between the patient group and the control group, we found that no statistically significant difference was detected. The BMD values were not significantly different between the groups of PPAR-γ Pro12Ala gene polymorphism. In conclusion, decreased BMD levels are frequent in β-thalassemia patients. PPAR-γ Pro12Ala gene polymorphism is not common in Egyptian patients with β-thalassemia. No significant relationship was found between the PPAR-γ Pro12Ala gene polymorphism and low BMD levels or osteopenia in Egyptian β-thalassemia patients. However, further studies on a larger population of Egyptian patients are needed to confirm this finding. Full article