Thalassemia Reports

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

Sickle cell disease (SCD) is a complex genetic disorder associated with multiple clinical manifestations, including increased susceptibility to bacterial and viral infections. This review article presents a comprehensive analysis of the current literature obtained from various online databases focusing on the relationship between SCD and infections caused by specific pathogens, such as pneumonia- and influenza-causing pathogens, Escherichia coli, Staphylococcus aureus, parvovirus, and hepatitis viruses. We discuss the underlying mechanisms that contribute to the increased susceptibility of individuals with SCD to these infections, primarily related to the pathophysiology of variant hemoglobin (HbSS) and its impact on vascular occlusion, hemolysis, functional asplenia, and immune deficiency. Moreover, we highlight the significant burden of infections on SCD patients, particularly children under five years of age, where they are the leading cause of morbidity and mortality. Additionally, we address the challenges faced in attempts for reducing the global mortality rate associated with SCD, particularly in low-income countries, where factors such as increased pathogen exposure, co-morbidities like malnutrition, lower vaccination rates, and limited healthcare facilities contribute to the high disease burden. This review emphasizes the need for targeted interventions, improved healthcare access, vaccination programs, and infection prevention strategies to alleviate the impact of infections on individuals with SCD and reduce the global mortality rates associated with the disease. Full article

Thalassemia is one of the most prevalent genetic disorders worldwide and has previously been found to have an association with several physiological and organ complications. Several studies have found both its positive and inverse correlation with the glomerular filtration rate (GFR). Therefore, in this meta-analysis, we tried to assess the accurate correlation of β-thalassemia major (β-TM) with GFR. We searched in Google Scholar, PubMed, and ScienceDirect, and from the initial 96 articles, we finally included 12 studies. The quality and publication bias assessment confirmed that all the studies were of high to moderate quality with no publication bias. The main outcome of the mean difference (MD) was −6.94, 95%CI: −20.69, 6.80 (p < 0.00001), which indicated a negative correlation of the GFR with β-TM. The sensitivity analyses found one study to be a slight outlier, and reanalyzing the data excluding that study, an MD was achieved of −16.46, 95%CI: −26.81, −6.11 (p < 0.00001), which provides even stronger support for our main outcome. Our result determined that the GFR is generally higher in healthy people as compared to β-TM patients. Full article

β-thalassemia, a congenital genetic hematological disorder characterized by the decrease or absence of β-globin chains, leads to a decrease in levels of Hemoglobin A. The affected individuals can be categorized into two cohorts based on transfusion dependency: transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT). Remarkably, despite the primary pathology lying in β-globin chain depletion, β-thalassemia also exhibits an intriguing association with iron overload. Iron metabolism, a tightly regulated physiological process, reveals a complex interplay in these patients. Over time, both cohorts of β-thalassemic individuals develop iron overload, albeit through distinct mechanisms. Addressing the diverse complications that arise due to iron overload in β-thalassemic patients, the utilization of iron chelators has gained a lot of significance. With varying efficacies, routes of administration, and modes of action, different iron chelators offer unique benefits to patients. In the Indian context, three commercialized iron chelators have emerged, showcasing a high adherence rate to iron chelator-based treatment regimens among β-thalassemic individuals. In this review, we explore the intriguing connection between β-thalassemia and iron overload, shedding light on the intricate mechanisms at play. We delve into the intricacies of iron metabolism, unveiling the distinct pathways leading to iron accumulation in these patients. Additionally, the therapeutic efficacy of different iron chelators in managing iron overload complications is mentioned briefly, along with the guidelines for their usage in India. Through this comprehensive analysis, we aim to deepen our understanding of β-thalassemia and iron overload, paving the way for optimized treatment strategies. Ultimately, our findings provide valuable insights into improving the care and outcomes of individuals affected by β-thalassemia. Full article

Background: HCV infection is very common in multi-transfused β-thalassemia patients who need regular blood transfusions. Aim: The study was conducted to determine the epidemiology of HCV in multi-transfused β-thalassemia patients in West Bengal, India. Methods: Over a span of six years, blood samples were collected from HCV sero-reactive β-thalassemia patients and processed for viral RNA isolation followed by nested RT-PCR for qualitative viremia detection. The HCV genotype was determined by amplifying the partial HCV core gene by nested RT-PCR followed by DNA sequencing and NCBI genotyping tools. Phylogenetic and phylogeographic studies were performed with MEGA-X and BEAST software, respectively. Results: Out of 917 multi-transfused HCV sero-reactive β-thalassemia patients, 598 (65.21%) were HCV RNA positive while 250 (41.80%) had spontaneously cleared the virus. A significant percentage of male patients from rural areas (p = 0.042) and economically backward class (p = 0.002) were at higher risk of HCV infection. Female thalassemia patients and individuals belonging to ages 11–15 years had higher chances of spontaneous clearance. The most prevalent circulatory HCV genotype was 3a (78.26%) followed by 1b (12.04%). Phylogeographic analyses revealed that the 3a strains share genomic similarities with strains from Pakistan, Sri Lanka, and Thailand, whereas the 1b strains share similarities with strains from Thailand, Vietnam, Russia, and China. Uncommon HCV subtypes 3g and 3i were also detected. Conclusion: The high prevalence of HCV infection among β-thalassemia patients of West Bengal, India indicates NAT-based assays should be implemented for HCV screening in donor blood to eliminate HCV by 2030. Full article

Severe Aplastic Anaemia (SAA) is a rare benign disease but carries a high-mortality rate unless treated in a specialised centre. Overwhelming laboratory and clinical evidence points to an autoimmune pathogenesis; although, the aetiology remains obscure in the majority of cases. The differential diagnosis in older patients is problematical and a diagnosis of hypoplastic myelodysplasia remains difficult. This review points out the difficulty in diagnosis without a specific test. Future research needs to define a specific diagnostic test and refine therapeutic interventions. Full article

Background: Alpha thalassemia is one of the most common human genetic abnormalities. More than 400 different variations of the α-globin protein have been introduced, most of which are not associated with noticeable clinical manifestations. The identification of all variants of Hb in different regions helps in acquiring comprehensive knowledge concerning thalassemia disease, and it can be used in preventive programs as well as prenatal diagnosis (PND). Aims: In the present study, we describe a new α1 gene mutation that leads to a frameshift after codon 83. Methods: As a plan for a national screening program of thalassemia, routine cell blood count (CBC) and Hb capillary electrophoresis tests were applied. After taking written informed consent, genomic DNA was extracted, and, for identifying common Mediterranean α-Globin gene deletion, multiplex Gap-PCR was performed; for detecting other mutations on α- and β-Globin genes, a DNA sequencing method was used. Results: The results of CBC and capillary electrophoresis tests showed microcytosis in a female subject. The sequencing of the α-Globin gene showed that the case is heterozygote for a single-nucleotide deletion at codon 83 of the α1-Globin Gene. We named this mutation Hb Adrian (α1: c.251–T), which is a novel mutation. The mentioned mutation was also detected in the subject’s mother. Conclusions: The introduced mutation (Hb Adrian) leads to a frameshift change that produces a protein with 100 amino acids, which in comparison to a normal α-chain is shorter, and its amino acids are altered after codon 83. This hemoglobin is undetectable via the use of electrophoresis. Although no major hematological abnormalities were observed in the carriers, Hb Adrian should be considered in screening programs to help prevent Hb H disease in high-risk couples. Full article

Murburn concept is a novel perspective for understanding cellular function, deeming cells as simple chemical engines (SCE) that are powered by redox reactions initiated by effective charge separation (ECS). The 1-electron active diffusible reactive (oxygen) species, or DR(O)S, equilibriums involved in these processes are also crucial for homeostasis, coherently networking cells, and rendering electromechanical functions of sensing and responding to stimuli. This perspective presents the true physiological function of oxygen, which is to enable ECS and the generation of DR(O)S. Therefore, DR(O)S must now to be seen as the quintessential elixir of life, although they might have undesired effects (i.e., the traditionally perceived oxidative stress) when present in the wrong amounts, places and times. We also elaborated that tetrameric hemoglobin (Hb) is actually an ATP-synthesizing murzyme (an enzyme working via murburn concept) and postulated that several post-translational modifications (such as glycation) on Hb could result from murburn activity. Murburn perspective has also enabled the establishment of a facile rationale explaining the sustenance of erythrocytes for 3–4 months, despite their lacking nucleus or mitochondria (to coordinate their various functions and mass-produce ATP, respectively). Although thalassemia has its roots in genetic causation, the new awareness of the mechanistic roles of oxygen-hemoglobin-erythrocyte trio significantly impacts our approaches to interpreting research data and devising therapies for this malady. These insights are also relevant in other clinical manifestations that involve respiratory distress (such as asthma, lung cancer, COVID-19 and pneumonia) and mitochondrial diseases. Herein, these contexts and developments are briefly discussed. Full article

Background: Although the global thalassemia zone covers Bangladesh, there are very limited studies conducted in this region. Therefore, the focus of our study is to understand the prevalence and burden of thalassemia and hemoglobinopathy in Bangladesh. Methods: The analysis was based on a retrospective evaluation of laboratory diagnoses between 2007 January and 2021 October. A total of 8503 specimens were sampled and analyzed which were either referred by corresponding physicians or self-referred. This was neither any epidemiological nationwide survey nor was the study population chosen randomly. Hematological data were obtained through capillary zone electrophoresis and corresponding complete blood count. Results: 1971 samples (~23.18% of the total) were found with at least one inherited hemoglobin disorder. The most common hemoglobin disorder observed was the hemoglobin E (Hb E) trait (10.67%), followed by the β-thalassemia trait (8.4%), homozygotic Hb E (1.59%), and Hb E/β-thalassemia (1.58%). Other variants found in this study with minimal percentages were Hb N-Seattle, Hb S, Hb D-Punjab, Hb Lepore, Hb C, Hb Hope, Hb H, and hereditary persistence of fetal hemoglobin. Discussion: The pattern of thalassemia and hemoglobinopathy in our study is diverse and heterogeneous. A broad and detailed spectrum of such inherited hemoglobin disorders will ultimately be helpful in implementing nationwide thalassemia management and strategy policy in Bangladesh. Full article

Allogeneic stem cell transplantation remains the only therapy for congenital, severe haemoglobinopathies that is able to reverse the pathological phenotype. In the severe form of thalassemia, regular transfusions are needed early in life. This population of patients could benefit from allo-SCT. However, the great efficacy of transplantation must be counterbalanced by the mortality and morbidity related to the procedure. In this short review, we reviewed the most recent data in the field of transplantation in transfusion-dependent thalassemia (TDT), highlighting the factors that have a major impact on outcomes. Full article

The human hemochromatosis protein HFE is encoded by the HFE gene and participates in iron regulation. The aim of this study was to detect the most frequent HFE gene mutations in a control population and in β-thalassemia trait (BTT) carriers, and to study their relationship with iron metabolism. Total blood count, hemoglobin electrophoresis at alkaline pH, HbA₂ quantification, iron (Fe), total Fe binding capacity and ferritin were assayed. HFE gene mutations were analyzed by real-time PCR. A total of 119 individuals (69 normal and 50 BTT) were examined. In the control group, 9% (6/69) presented a codon 282 heterozygous mutation (C282Y), and 19% a codon 63 mutation (H63D) (13/69, 11 heterozygotes and 2 homozygotes). In the BTT group, 3 carriers (6%) were heterozygous for C282Y, 14 (28%) for H63D, 1 (2%) for a codon 65 mutation and 1 (2%) was H63D and C282Y double heterozygous. Control group Fe metabolism did not show significant differences (p > 0.05) according to whether or not they carried an HFE gene mutation; while the BTT group with and without HFE mutation showed higher Fe and ferritin than the control group (p < 0.05). However, no increases in iron parameters were detected in BTT carriers that simultaneously exhibited an H63D mutation compared to BTT subjects without a mutation. Therefore, the iron metabolism alterations observed in BTT carriers could not be attributed to the presence of HFE gene mutations. It is likely that BTT individuals have other genetic modifiers that affect their iron balance. Full article

Genetic polymorphisms in Quantitative Trait Loci (QTL) genes such as BCL11A, HBS1L-MYB and KLF1 have been reported to influence fetal hemoglobin (HbF) levels. This prospective study was planned to evaluate the role of genetic polymorphisms in QTL genes as determinant of HbF levels in beta thalassemia major patients. The study was carried out on 100 thalassemia major patients. Blood samples were collected in EDTA and plain vials for biochemical and molecular evaluation. The BCL11A, HBS1L-MYB and KLF1 genotypes were determined using a polymerase chain reaction (PCR)-based method. Red Blood Cell (RBC) indices and HbF levels were assessed. In silico analysis was assessed using loss-of-function tool (Lof Tool). Statistical difference and genetic comparisons between groups were evaluated by using SPSS for Windows, version 16.0 (SPSS Inc., Chicago, IL, USA). Comparisons between quantitative variables were carried out after data explored for normality using Kolmogorov–Smirnov test of normality. Logistic regression was used for computation of ORs and 95% CIs (Confidence Interval). We observed association of HbF levels in thalassemia major patients with the polymorphisms in BCL11A (rs11886868 rs7557939; rs1427407 and rs766432) and HBS1L-MYB (rs9399137) gene. The results of this study indicated that the presence of polymorphisms on modifier genes are strongly associated with an increase in HbF levels in thalassemia major patients. Further research with a larger sample size and with other genes of modifier genes is required. Full article

Luspatercept has been shown to act as a ligand trap, selectively suppressing the deleterious effects of GDF11 that blocks terminal erythroid maturation, restoring normal erythroid differentiation and improving anemia in animal models of β-thalassemia. Effective doses of luspatercept achieved hemoglobin increase within 7 days of the first dose, and plasma half-life supports subcutaneously administration every 21 days in adults with β-thalassemia. A Phase 3, placebo-controlled 1-year study with starting dose of 1.0 up to 1.25 mg/kg every 21 days achieved ≥33% reduction in red cell transfusion volume in 21.4% of adult transfusion-dependent β-, HbE/β-thalassemia patients on luspatercept vs. 4.5% on placebo over a fixed 12-week period, and 41.1% of patients in luspatercept vs. 2.7% placebo in any 24-week period. Luspatercept allowed ≥1.0 and ≥1.5 g/dL increase in hemoglobin from baseline in 77% and 52.1% of adult non-transfusion-dependent β-, HbE/β-thalassemia patients vs. 0% placebo over a 12-week interval. Although not significant, a greater improvement in patient-reported outcomes was observed with luspatercept. Luspatercept had a manageable safety profile with notable adverse effects of venous thromboembolism in 3.6% of transfusion-dependent β-thalassemia vs. 0.9% of placebo and extramedullary hematopoiesis in 6% of non-transfusion-dependent β-thalassemia vs. 2% of placebo. The pediatric study started patients’ enrollment. Full article

Next-generation ektacytometry provided by the osmoscan module of the Laser Optical Rotational Red Cell Analyser (LoRRca) MaxSis is, so far, one of the best complementary diagnostic tools for congenital rare anaemias due to red blood cell defects. Osmotic gradient ektacytometry (OGE) is currently considered the gold standard for the diagnosis of red cell membrane disorders, especially hereditary spherocytosis (HS). Impairment of red cell deformability, leading to a decrease in red cell survival rate, is the common trait of hereditary haemolytic anaemias; in general, it is the consequence of an abnormal cell shape, increased rigidity or dehydration. Up to now, the next-generation ektacytometry has been mainly used for the differential diagnosis of red blood cell membranopathies, but experience with structural hemoglobinopathies and thalassemia is still scarce. However, recently, many new forms of therapy are being developed for the treatment of hemoglobinopathies, particularly sickle-cell disease and β-thalassemia; clinical interest in ektacytometry is increasing and should be further explored. Here, we have evaluated the OGE profiles provided by the osmoscan module of the LoRRca ektacytometer in 96 patients with different hemoglobinopathies, both structural and thalassemia, with the aim of analysing their usefulness for the early diagnosis of these disorders either individually or in co-inheritance with other hereditary RBC defects. In addition, this study aims to improve our knowledge of the contribution of red cell deformability, osmotic fragility and intracellular viscosity to the physiopathology of haemolysis, especially when these disorders are a cause of rare anaemia. From this study, we conclude that the osmoscan profile provides complementary information on red cell deformability and hydration homeostasis that may contribute to the better understanding of the physiopathology of decreased red cell survival and hemolysis which is present in some patients. Full article