Causes of Death and Mortality Trends in Individuals with Thalassemia in the United States, 1999-2020.

Purpose: Our study aims to describe the mortality trends and disparities among individuals with thalassemia in the United States (US). Patients and Methods: We used CDC WONDER database to calculate the age-adjusted mortality rates (AAMRs) per 1,000,000 individuals and used the Joinpoint Regression Program to measure the average annual percent change (AAPC). Subgroup evaluations were performed by sex, age, race, census region, and urbanization level. Results: From 1999 to 2020, there were 2797 deaths relatd to thalassemia in the US. The AAMR of thalassemia-related death showed a decreasing trend from 0.50 (95% CI, 0.41-0.58) in 1999 to 0.48 (95% CI, 0.41-0.55) in 2020 with the AAPC of -1.42 (95% CI, -2.42, -0.42). Asians have the highest AAMR (1.34 [95% CI, 1.20-1.47]), followed by non-Hispanic Blacks (0.65 [95% CI, 0.59-0.71]), non-Hispanic Whites (0.32 [95% CI, 0.30-0.33]), and Hispanics (0.11 [95% CI, 0.08-0.14]). Cardiovascular disease remains the leading cause of death among individuals with thalassemia. The urban population has a higher AAMR than the rural population (0.43 [95% CI, 0.41-0.45] vs 0.29 [95% CI, 0.26-0.32]). Conclusion: Our study calls for targeted interventions to address the racial and geographic disparities existed among individuals of thalassemia in the US.

Distinguishing Iron Deficiency Anemia From Beta-Thalassemia Trait: Comparative Analysis of CRUISE Index and Other Traditional Diagnostic Indices.

Introduction Iron deficiency anemia and beta-thalassemia trait are two common and important differentials of microcytic hypochromic anemia. Various discrimination indices using two or more common complete blood cell count (CBC) parameters have been used to distinguish between the two since 1973. Recently, a new discriminant index, the CRUISE index, was proposed in the year 2019. The efficacy of various older indices along with the CRUISE index was evaluated for patients in our geographical area. Materials and method Ours was a laboratory-based, cross-sectional study where 100 patients, based on inclusion and exclusion criteria, with microcytic hypochromic anemia were evaluated for CBC parameters along with serum ferritin and hemoglobin-high performance liquid chromatography (Hb HPLC). A total of eight discrimination indices namely, Mentzer, Srivastava, Shine & Lal, Green & King, RDWI, England & Fraser, Kerman I and CRUISE index were used and evaluated for their diagnostic efficacy using different statistical parameters. ROC curves were obtained and a new cut-off value was proposed for our population. Data was analysed using Microsoft Excel (Microsoft® Corp., Redmond, WA, USA) and SPSS v29.0.2.0 (20) (IBM Corp., Armonk, NY, USA). Results Out of the total 100 cases, 39 were beta-thalassemia trait and 61 were iron deficiency anemia cases. The average age was 36.7 (±12.7 SD) years. Among the 73 females, 43 were diagnosed as iron deficiency anemia (IDA) and 30 as beta-thalassemia trait (BTT) cases. Among the 27 males, 18 were diagnosed as IDA and nine as BTT cases. The mean values were significantly lower in IDA patients for mean corpuscular volume (MCV) (p=.008), mean corpuscular haemoglobin (MCH) (p=.003), and mean corpuscular haemoglobin concentration (MCHC) (p=.003) and significantly higher for red cell distribution width (RDW) (p=.020). The mean ferritin levels in cases of IDA were 7.61 (±3.75) mcg/L and in BTT were 87.09 (±66.77 SD) mcg/L. The mean HbA2 levels in IDA cases were 2.75% (±0.41% SD) and BTT cases were 5.57% (±0.73% SD). CRUISE index revealed the highest AUC (0.934), YI (76.21) and accuracy (90%) followed by the Mentzer index with a diagnostic accuracy of 81%. Shine & Lal index revealed the lowest AUC (0.710), YI (3.28) and accuracy (41%). Conclusion CRUISE index, which was recently proposed, was ranked 1st in terms of AUC, YI, and accuracy and was considered 2nd best in terms of sensitivity for differentially diagnosing the two conditions. Mentzer index, a commonly used index, also revealed a high diagnostic accuracy in our study for differentiating BTT from IDA. CRUISE index being a novel index, more research work needs to be carried out in various other geographical setups to evaluate the efficacy of this index.

Dominant Beta Thalassemia: A Very Rare Cause of Thalassemia in a Mediterranean Country.

Beta thalassemia is one of the monogenic disorders characterized by decreased production of ß-globin chains and various types of mutations have been reported to cause thalassemia phenotype. On the other hand, rare mutations also affect and diversify the disease spectrum. Herein, we present an anemic patient from Turkey diagnosed with dominant ß thalassemia due to a heterozygous mutation in exon 3 of the HBB gene.

Soluble Fms-like tyrosine kinase-1 as an endothelial dysfunction biomarker associated with pulmonary hypertension in adult patients with beta-thalassemia major.

The etiology of vascular problems in beta-thalassemia has been linked to endothelial damage. Antiangiogenic proteins such as soluble Fms-like tyrosine kinase-1 (sFLT-1) inhibit the signaling of vascular endothelial growth factor and placental growth factor, resulting in a decrease in the development of new blood vessels. Additionally, they promote the maturation of existing blood vessels and lead to endothelial dysfunction. This study aimed to assess the role of sFLT-1 in adult patients with beta-thalassemia major (TM) as a biomarker of endothelial dysfunction and its association with pulmonary hypertension (PHT). A total of 90 subjects were recruited and categorized into two groups: 45 patients with beta-TM, who were further divided based on the presence or absence of PHT, and 45 healthy individuals served as a control group. Serum sFLT-1 was determined using the enzyme-linked immunosorbent assay technique. The results revealed that Beta-TM patients had higher sFLT-1 levels than the control group. In addition, patients with PHT had significantly higher sFLT-1 levels compared to those without PHT. The levels of sFLT-1 were positively correlated with von Willebrand factor, serum ferritin, and high-sensitivity C-reactive protein. Regression analyses demonstrated a significant association between high sFLT-1 levels and the occurrence of PHT. Additionally, sFLT-1 (at a cutoff value of 8.84 pg/mL) demonstrated a sensitivity of 83.30% and a specificity of 80.0% in diagnosing thalassemic patients with PHT. In conclusion, beta-TM patients with elevated serum levels of sFLT-1 are at risk of developing endothelial dysfunction and subsequent development of PHT.

Skin complications during iron chelation therapy for beta-thalassemia: overview and treatment approach.

Thalassemia is an inherited genetic disorder of hemoglobin that affects a large population worldwide, and it is estimated that between 50,000 and 60,000 infants with thalassemia are born each year. The most common treatment for thalassemia is blood transfusion, which leads to iron overload. This in itself is a serious clinical condition, and is commonly managed with iron chelation therapy. However, iron chelators can cause various skin complications, including hyperpigmentation, skin rash, itching, and photosensitivity. These skin side effects can impact patients' quality of life. Therefore, this article provides a comprehensive overview of skin complications caused by iron chelators, along with a proposed comprehensive approach to their management in patients with beta-thalassemia. Key strategies include patient education, regular skin assessment, sun protection measures, symptomatic relief with topical corticosteroids and antihistamines, and consideration of treatment modification if severe complications occur. Collaboration between hematologists and dermatologists, along with psychological support and regular follow-up, is an essential component of this multidisciplinary approach. By implementing these strategies, healthcare providers can optimize skin care for patients with beta-thalassemia treated with iron chelators and improve their quality of life.

Mutation Analysis of Exon 1 in the Hemoglobin Subunit Beta (HBB) Gene in Beta-Thalassemia.

Introduction Thalassemia is a widely prevalent monogenic hematological disorder found worldwide. It exists in two forms: alpha- and beta-thalassemia. Alterations in the hemoglobin subunit beta (HBB) gene cause beta-thalassemia, with missense and point mutations affecting beta-globin synthesis. Consequently, genetic screening for beta-thalassemia is essential for genetic counseling, carrier screening, and prenatal diagnosis. Aim and objective This study aims to examine and identify mutations in the exon 1 region of the HBB gene in beta-thalassemia patients from the Vijayapura region. Methods This study involved 47 clinically diagnosed children with beta-thalassemia from a hospital in Vijayapura, India. Detailed clinical histories of all patients were recorded. Genomic DNA was extracted from the blood samples of these patients and subjected to polymerase chain reaction (PCR) using exon-specific primers for the HBB gene. The PCR products were then sequenced using the capillary-based Sanger sequencing method to identify mutations in the HBB gene. Results A total of 47 clinically diagnosed beta-thalassemia patients were included in the study, comprising 30 males and 17 females, aged between one and 20 years. Sequencing analysis of exon 1 in the beta-globin gene identified 17 beta-thalassemia variants. The most common mutation observed was T>G, G>C, C>A, and C>T in the exon 1 region of the HBB gene.  Conclusion This study identifies the pattern of beta-thalassemia mutations, aiding in the prevention of the disorder through prenatal diagnosis and genetic counseling. Mutations can alter codon sequences, affecting protein production. Research highlights the importance of a primary prevention program to analyze mutations and sequence variations at the molecular level, thereby helping to address numerous genetic disorders.

Exploring the bone marrow micro environment in thalassemia patients: potential therapeutic alternatives.

Genetic mutations in the ß-globin gene lead to a decrease or removal of the ß-globin chain, causing the build-up of unstable alpha-hemoglobin. This condition is referred to as beta-thalassemia (BT). The present treatment strategies primarily target the correction of defective erythropoiesis, with a particular emphasis on gene therapy and hematopoietic stem cell transplantation. However, the presence of inefficient erythropoiesis in BT bone marrow (BM) is likely to disturb the previously functioning BM microenvironment. This includes accumulation of various macromolecules, damage to hematopoietic function, destruction of bone cell production and damage to osteoblast(OBs), and so on. In addition, the changes of BT BM microenvironment may have a certain correlation with the occurrence of hematological malignancies. Correction of the microenvironment can be achieved through treatments such as iron chelation, antioxidants, hypoglycemia, and biologics. Hence, This review describes damage in the BT BM microenvironment and some potential remedies.

Correlation between plasma biochemical parameters and cardio-hepatic iron deposition in thalassemia major patients.

INTRODUCTION: Major Thalassemia patients suffer from iron overload and organ damage, especially heart and liver damage. Early diagnosis and treatment with a chelator can reduce the complications and mortality of iron overload. Therefore, we aimed to investigate the biochemical and hematological predictors as an alternative and indirect indicator of iron deposition in heart and liver cells in comparison with the MRI T2* method as the gold standard. MATERIAL AND METHOD: MRI T2* was evaluated in the heart and liver tissues of 62 major beta-thalassemia patients undergoing regular transfusion and chelator therapy. Biochemical and hematological factors were also measured, including serum ferritin, serum electrolytes, liver enzymes, hemoglobin, blood glucose, and serum magnesium. The correlation between these factors was assessed using statistical evaluations. RESULT: Serum ferritin had a positive and significant correlation with liver siderosis based on MRI T2* (p-value = .015), and no significant association was observed with cardiac siderosis (p-value = .79). However, there was a significant positive correlation between cardiac iron deposition and fasting blood sugar level (p-value = -.049), and plasma level of liver enzymes (alanine aminotransferase (ALT) (p-value = .001), aspartate aminotransferase (AST ((p-value = .01)). Moreover, there was a significant negative correlation between cardiac iron overload and plasma magnesium level (p-value = .014). According to MRI T2*, there was no significant correlation between cardiac and hepatic iron overload (p value = .36). CONCLUSION: An increase in blood sugar or liver enzymes and a decrease in serum magnesium was associated with an increase in cardiac iron overload based on MRI T2*. Liver iron overload based on MRI T2* had a significant correlation with serum ferritin.

Assessing NESTROFT as a preliminary screening tool for thalassemia in the Malayali tribes of Dharmapuri district, Tamil Nadu, India.

Background: Mutations affecting transcription, translation, or beta-globin stability, among other stages of beta-globin production, cause beta-thalassemia. Methods: Beta-thalassemia results in a high red blood cell count with a low mean corpuscular volume (60-70fl) and mean corpuscular hemoglobin (19-23pg), and Naked Eye Single Tube Red Cell Osmotic Fragility Test (NESTROFT) is recommended for mass screening of populations. Among tribals in Dharmapuri district, this cross-sectional analysis evaluated the efficacy of RBC and NESTROFT against HPLC, regarded as the gold standard, in a study involving 484 subjects. Results: Findings indicated that out of the 484 samples, 73 tested positive for the beta-thalassemia trait through HPLC. The NESTROFT test demonstrated 87% sensitivity, 98.5% specificity, a positive predictive value of 99.3%, and a negative predictive value of 73.3%. In the multivariate analysis, NESTROFT and hemoglobin showed high significance with P values of 0.003 and 0.000, respectively. Conclusion: NESTROFT's high sensitivity is particularly noteworthy due to the absence of research among the Malayali tribes in the Dharmapuri district. Adoption of this preliminary test shows promise in detecting the disease at the local level, providing important information for early detection, especially considering the sizeable tribal population.

The Relevance of ß-Thalassemia Heterozygosity in Pediatric Clinical Practice: Croatian Experience.

(1) Background: Thalassemia syndromes are common monogenic disorders that represent a significant global health issue. No systematic epidemiological or molecular investigations on thalassemias in the Croatian population have been reported to date. (2) Methods: This prospective study included 70 children with a presumptive diagnosis of thalassemia and their 42 first-degree relatives. Molecular characterization was performed using direct sequencing and gap-PCR methods. (3) Results: We identified 46 (30 children and 16 first-degree relatives) ß-thalassemia heterozygous carriers from 24 unrelated families, carrying eight different mutations and one hemoglobin variant. Five variants account for approximately 85% of all affected ß-globin alleles: Hb Lepore-Boston-Washington (32.6%), HBB:c.93-21G>A (19.6%), HBB:c.315+1G>A (13.1%), HBB:c.92+1G>A (10.9%), and HBB:c.92+6T>C (8.7%) variants. (4) Conclusions: ß-thalassemia carriers need more detailed genetic profiling since genetic modifiers can significantly impact their phenotype. Our study provides important new insights into the relevance of ß-thalassemia heterozygosity in pediatric clinical practice.

Assessing Psychological Disorders in Turkish Adolescents with Transfusion-Dependent Thalassemia.

We investigated depression and anxiety levels and related psychological disorders in adolescents with transfusion-dependent thalassemia (TDT) in this study. The study was conducted in two pediatric hematology outpatient clinics and included adolescents with TDT (14.8 ± 2.4 years, n = 40) in the study and compared them with the healthy age-matched control group (14.3 ± 2.3 years, n = 62). The Turkish version of the Revised Child Anxiety and Depression Scale (RCADS) was used to determine depression, anxiety, and related psychologic disorders (obsession, panic disorder, social phobia). Depression, anxiety, obsession, panic disorder, and social phobia scores were significantly higher in the patient group compared with the control (all p < 0.05). Ferritin levels were positively correlated with total depression, general anxiety, separation anxiety, and social phobia scores, but transfusion frequency and young age were the confounding factors. Patients in early adolescence and those who require more frequent blood transfusions are at higher risk of developing psychological disorders; routine screening for mood disorders should be warranted. Serum ferritin level may be a good warning indicator for early recognition of psychologic disorders in TDT patients.

Serum visfatin level in ß-thalassemia and its correlation with disease severity.

Thalassemia is a group of genetic hematological conditions characterized by the defective synthesis of one or more hemoglobin chains. This genetic anomaly alters globin chain balance, causing hemolysis, ineffective erythropoiesis, and chronic inflammatory diseases. The proinflammatory adipocytokine visfatin is predominantly produced in visceral adipose tissue. Its evaluation in individuals with thalassemia may provide valuable insights into the assessment of disease severity. The aim of this study was to investigate the potential role of visfatin in the development of ß-thalassemia and its association with the severity of the illness. The study included 40 patients with ß-thalassemia and ten healthy individuals matched by age and sex. Serum visfatin level was measured using ELISA. We found that individuals with ß-thalassemia major had significantly higher levels of serum visfatin than those with ß-thalassemia minor and the control group (P < 0.001). A receiver operating characteristic curve revealed that serum visfatin levels were different in the three groups. Our results suggest that the serum level of visfatin is significantly correlated with the severity of ß-thalassemia.

Genetic Correlation of HBB, HFE and HAMP Genes to Endocrinal Complications in Egyptian Beta Thalassemia Major Patients.

Iron loading is regarded as the primary cause of endocrine abnormalities in thalassemia major patients. Thus, the purpose of the current research was to explore the impact of thalassemia genotypes, hepcidin antimicrobial peptide (HAMP) and hereditary hemochromatosis (HFE) gene variants, and hepcidin expression on serum ferritin and endocrinal complications in thalassemia patients. The study comprised fifty beta-thalassemia cases and fifty age- and sex-matched controls. Genotyping of the Beta-globin gene (HBB), HAMP, and exon 2 of the HFE gene was performed using Sanger sequencing. C282Y (c.845G > A) variant of the HFE gene was determined by PCR-RFLP. Hepcidin mRNA expression was assessed by qRT-PCR. Biochemical and hormonal studies were done for all patients. Hypogonadism and short stature were found in 56% and 20% of the investigated cases, respectively. Molecular studies reported a statistically higher frequency of the HAMP variant c.-582A > G in thalassemic patients than controls. Significant downregulation of hepcidin expression was found in cases compared to healthy subjects that was significantly associated with short stature. Considering the thalassemia alleles, the IVSI.1G > A (ß0) allele was statistically related to hypogonadism. Our results proposed that thalassemia genotypes and downregulated hepcidin expression were the potential risk factors for endocrinopathies in our cases. We also demonstrated an increased incidence of the HAMP promoter variant c.- 582A > G that might have a role in the pathogenesis of iron overload in thalassemic cases. Significant downregulation of hepcidin expression, that contributes to increased iron burden, could be used as a future therapeutic target in these patients.

Serum Iron and Ferritin Levels in Beta Thalassemia Carriers in Duhok Governorate, Iraq.

Background Thalassemia and iron deficiency anemia (IDA) account for most cases of microcytic hypochromic anemia. It is a common misconception that iron deficiency does not occur in thalassemia. However, studies have found that iron deficiency can coexist in carriers of beta thalassemia. Objective The aim of this study was to determine the prevalence of iron deficiency and iron overload in carriers of beta thalassemia in Duhok, Iraq. Patients and methods This prospective cross-sectional study included 250 patients with beta thalassemia carriers attending Kurdistan Private Hospital Laboratory Department from July 2021 to June 2023. Patients with microcytic hypochromic blood picture were tested for HbA2 levels, and those with a level >3.7% were included in the study and were tested for serum iron and serum ferritin levels. Results The age range was 15-80 years, with a mean of 25 years, and the male-to-female ratio was 1.5:1. The prevalence of iron deficiency in beta thalassemia carriers was 16% (N = 40). The prevalence of iron overload was 8.4% (N = 21). There was a significant statistical difference among those with iron deficiency, normal iron status, and iron overload in terms of hemoglobin level (P=0.001), RBC count (P=0.012), HbA2 (P=0.015), and serum ferritin (P < 0.0001). Conclusion Iron deficiency is more prevalent in beta thalassemia carriers than iron overload, necessitating proper assessment of iron status in patients with beta thalassemia carriers. Those with abnormal iron status need effective treatment to optimize the overall outcomes in patients with beta thalassemia carriers.

Health-related Quality of Life of Omani Adult Patients with ß-Thalassemia Major at Sultan Qaboos University Hospital.

Objectives: The impact of beta-thalassemia major (ß-TM) on health-related quality of life (HRQoL) in Oman is not yet known. Affected individuals suffer from a wide range of physical, mental, and social consequences due to the need for regular hospital visits for blood transfusions and complications related to iron overload. This study aimed to assess the HRQoL of adult patients with ß-TM attending a single tertiary care center in Muscat, Oman, to identify factors influencing Omani patients' QoL for improved management and counseling. Methods: A cross-sectional study was conducted among adult patients (≥ 18 years) with ß-TM at Sultan Qaboos University Hospital between September and November 2022. A validated Arabic version of the self-reported 36-item short-form health survey was used to determine HRQoL. Results: A total of 78 patients with ß-TM were enrolled in the study; 53.8% were male and the mean age was 26.0±0.8 years, ranging from 21-53 years. Most patients were from Al Batinah North governorate (n = 21; 26.9%) and Muscat (n = 20; 25.6%), unmarried (n = 44; 56.4%), did not have university-level education (n = 45; 57.7%), and were unemployed (n = 44; 56.4%). The HRQoL domain with the highest score was role limitations due to emotional problems (median score = 100), while general health and vitality received the lowest scores (mean scores were 60.2±15.9 and 59.1±20.5, respectively). Several variables were associated with better HRQoL in certain domains, including being married, having a high level of education, being employed, exercising regularly, and receiving family support (p < 0.05). However, iron overload and having ≥ 3 ß-TM-related disease complications were associated with poorer general health scores (p = 0.031 and 0.038, respectively), while a history of mental issues was associated with poorer scores in six out of eight HRQoL domains (p < 0.05). Moreover, negative perceptions regarding the social impact of the disease including delayed marriage, workplace difficulties, and reduced academic achievement were associated with poorer HRQoL in various domains (p < 0.05). Conclusions: Although the studied sample reported generally good QoL, several factors were found to affect HRQoL in various domains. Healthcare providers should prioritize maintaining acceptable iron overload levels in Omani patients with ß-TM to help avoid the development of disease-related complications, thereby ensuring better control of their clinical conditions and consequently improving their HRQoL.

Autosomal Recessive Hyper-IgE Syndrome in a Child With Beta Thalassemia Trait: A Case Report.

Autoimmune diseases are multifaceted disorders, and their coexistence with other conditions can present unique challenges in diagnosis and management. Here, we report a rare case of autosomal recessive hyper-IgE syndrome (AR-HIES) in a child with beta thalassemia trait. AR-HIES is a distinct immunodeficiency disorder characterized by severe eczema and recurrent bacterial and viral infections, particularly affecting the sinopulmonary system. This case highlights the importance of recognizing and managing the co-occurrence of rare genetic conditions, as it can impact treatment strategies and familial counseling. This unique case of AR-HIES in a child with beta thalassemia trait underscores the complexity of autoimmune disorders and the need for comprehensive evaluation in patients presenting with multiple clinical manifestations.

Ovarian Tissue Cryopreservation for Fertility Preservation in Patients with Hemoglobin Disorders: A Comprehensive Review.

Hemoglobin diseases like sickle cell disease (SCD) and ß-thalassemia (BT) present fertility challenges for affected patients. SCD and BT result from abnormal hemoglobin production or structure and pose numerous health concerns. Despite medical advancements improving the quality of life or even providing cures, SCD and BT pose unique fertility concerns for women. Young women with these disorders already contend with reduced ovarian reserve and a narrower fertile window, a situation that is compounded by the gonadotoxic effects of treatments like medications, transfusions, stem cell transplants, and gene therapy. While crucial for disease control, these interventions may lead to reproductive health issues, increasing infertility and early menopause risks. Ovarian tissue cryopreservation (OTC) offers potential for future motherhood to women with hemoglobin disorders facing infertility related to curative treatments. OTC involves surgically removing, preparing, and freezing ovarian tissue containing primordial follicles capable of producing mature oocytes, offering advantages over oocyte cryopreservation alone. However, the application of OTC for patients with hemoglobin disorders presents unique challenges, including special health risks, financial barriers, and access to care. This comprehensive literature review delves into the current state of ovarian tissue cryopreservation for fertility preservation in patients with hemoglobin disorders. Empowering patients with informed reproductive choices in the context of their hemoglobin disorders stands as the ultimate goal.

Hematopoietic Stem Cell Transplantation in Children with Sickle Cell Disease and Thalassemia Major: A National Database Study.

In patients with sickle cell disease (SCD) and beta-thalassemia major (TM), allogeneic hematopoietic stem cell transplantation (HSCT) was considered the only curative treatment option with a good survival rate. However, with the recent approval of gene therapies, more information is needed to understand the benefits and risks of these interventions. We performed a retrospective analysis of the Kids Inpatient Database to describe demographic features, short-term complications, and hospital charges of patients with SCD and TM treated with HSCT during 2006-2019 in the United States. The database was filtered using the International Classification of Diseases, 9th and 10th edition codes to identify children under 20 years of age with SCD or TM who underwent HSCT. A total of 513 children with SCD or TM who received HSCT were analyzed. The prevalence of HSCT per 1000,000 U.S. population increased from 0.31 in 2006 to 1.99 in 2019 (p < 0.001). The median age of children with SCD who underwent HSCT was 10 (6-15) years, and that for TM was 6 (3-11.5) years (p < 0.001). The combined mortality rate was 4% (2.4%-6.6%) but higher in the TM group. The length-of-stay and total charges were higher in the TM population (p < 0.01). This study provides national data on HSCT among hospitalized children with SCD and TM in the United States, demonstrating an increasing use of HSCT between 2006 and 2019. Although hospital mortality of HSCT in these conditions is low, it still represents a challenge, especially in TM patients.

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

The phenotype of ß-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-ß thalassemia. However, the role of alpha globin gene alterations (deletions and triplication) is not well illustrated in homozygous ß-thalassemia. Here we evaluated the role of alpha globin gene alterations in 122 ß-thalassemia patients having IVS1-5 (G > C) homozygous mutation. ß-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 3.7 kb deletion (-α3.7) mutation and three patients had 4.2 kb 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/ß 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 ß-thalassemia.

The Characteristics of Compound Heterozygosity for Hemoglobin G-Makassar with Hb E in Malaysia.

Background: Human hemoglobin of G-Makassar and hemoglobin E (Hb E) are hemoglobin variants that affect Beta (ß) globin. Hb G-Makassar is a very rare variant while Hb E is estimated to affect at least one million people worldwide. Both Hb G-Makassar and Hb E can be inherited in the heterozygous, homozygous or compound heterozygous state. This case series describes the characteristics of four individuals with compound heterozygosity for Hb G-Makassar/Hb E cases in Malaysia. To the best of our knowledge, these are the only four individuals with this genotype reported in the literature. Case Series: We present four cases of compound heterozygosity for Hb G-Makassar/Hb E identified from October 2014 to January 2021. All the cases were incidental findings whereby the screening Hb analysis showed the presence of peaks in both Hb S and Hb E zones on capillary electrophoresis (CE) and cation-exchange high-performance liquid chromatography (HPLC). Molecular analysis confirmed the findings of compound heterozygous Hb G-Makassar/Hb E. Two cases had a history of anemia secondary to unrelated conditions that resolved with treatment of the underlying cause. The other two cases were asymptomatic individuals who were detected through Malaysia's National Thalassemia Screening program. On the last follow-up, all the individuals were well, non-transfusion dependent, and had no reported history of chronic anemia, bleeding, hemolysis or thromboembolism complications. Conclusion: The cases reported here highlight the possibilities for rare compound heterozygous states in multi-ethnicity populations such as Malaysia. Compound heterozygous Hb G-Makassar/Hb E individuals are clinically silent with laboratory values suggesting microcytic and hypochromic red blood cells. Further local epidemiology or population studies with genotyping tests are required for a better understanding of the diversity of its clinical phenotype.