Types Of Thalassemia Research Articles

Beta-Thalassemia Haplotypes in Southwest of Iran

Background: Thalassemia is a widespread disease affecting people across various ethnicities and regions. In comparison to previous studies conducted in different regions of Iran, such as those in Lorestan and Sistan-Baluchestan, this study highlights unique mutation patterns prevalent in the southwestern population, emphasizing the genetic heterogeneity in this region. The identification of common mutations of beta-thalassemia in various ethnic groups within the nation is regarded as a practical solution for thalassemia prevention and prenatal diagnosis. Materials and Methods: In this retrospective observational study, the medical records of 545 patients with various types of beta-thalassemia (silent, minor, intermediate, and major), referred to the center at Baqaei 2 hospital over a 14-year period (2008–2022), were examined. The age range of patients spanned from a 2-month-old fetus to a 34-year-old individual. Their mutations and thalassemia types were determined and confirmed using molecular methods, including PCR-ARMS (polymerase chain reaction-amplification refractory mutation system) and sequencing. The results were analyzed using SPSS software. Results: The study examined 545 patients and identified 81 types of mutations. The most frequent mutations observed were CD36-37(-T)/N, IVSII-1/N, and IVS1-110(G>A). The study also noted population heterogeneity, reflected in the wide range of mutations found in the region. Among the patients, 6 had the silent form of beta-thalassemia, 488 had the minor form (464 patients and 24 fetuses), 9 had the intermediate form (8 patients and 1 fetus), and 42 had the major form (26 fetuses and 16 adults). Conclusion: The identification of prevalent beta-thalassemia mutations facilitates disease control and prevention programs and is crucial for the identification of various beta-thalassemia gene mutations. This should be re-evaluated periodically. Observing a wide range of beta-thalassemia genotypes in the southwestern region of Iran suggests gene flow; thus, identifying these genotypes is instrumental in preventing and controlling the disease.

Evaluation of the immunization efficacy and adverse reactions of hepatitis B vaccination in children with thalassemia minor

ObjectiveTo assess the immunization efficacy and incidence of adverse reactions after hepatitis B vaccination in children with thalassemia based on data from real-world studies.MethodsA total of 625 children were recruited into this cross-sectional study. Subgroup analyses of different thalassemia types were performed using binary logistic regression, the factors affecting HBsAb levels were identified using multiple linear regression, and the dose-response relationship between the duration of immunization and seroconversion was explored using the restricted cubic spline (RCS) model to further assess the protective duration of the hepatitis B vaccine.ResultsHBsAb positivity in enrolled children was 87.3% in the thalassemia group and 81.4% in the control group. Multifactorial analysis revealed that the duration of immunization, age at completion of vaccination, and whether the first dose was delayed were significant factors influencing HBsAb levels in children (P < 0.05). The threshold for HBsAb positivity may be reached when the immunization duration reaches approximately 30 months. A subgroup analysis revealed that the HBsAb positivity rate was lower in children with β-thalassemia minor compared to those with α-thalassemia minor (P = 0.001, 95% CI: 0.097 ∼ 0.536). Adverse reactions after hepatitis B vaccination were dominated by general reactions, with a statistically significant difference in injection-site redness and swelling between the thalassemia and control groups (P < 0.05).ConclusionsThe immunization response to the hepatitis B vaccine in children with thalassemia minor was comparable to healthy children, with no abnormal adverse effects seen.

Genotype Distribution and Clinical Characteristics of Thalassemia Patients Needing Transfusion in Yangjiang, Western Guangdong

Plain Language SummaryThis study is a retrospective research that investigates the genotype distribution and iron metabolic imbalance in thalassemia patients requiring blood transfusion. Eighty-four thalassemia patients needing transfusion were enrolled in the study and underwent genotype analysis. Among these patients, 56 were transfusion-dependent and 28 were non-transfusion-dependent. Of the 56 transfusion-dependent patients, 48 were observed for 3 years, and their iron overload status was analyzed in this study. Our research found that among the 84 thalassemia patients needing transfusion, there were six types of α-thalassemia deletions and nine types of β-thalassemia mutations. Among the 56 transfusion-dependent patients, three types of α-thalassemia genotypes and 15 types of β-thalassemia genotypes were identified. Among the 48 transfusion-dependent thalassemia patients observed for 3 years, 40 patients exhibited iron overload with SF levels exceeding 1,000 ng/mL. The recent SF levels were lower than those 3 years ago. Our study found that β-thalassemia is the most common type of transfusion-dependent thalassemia. Standard blood transfusion and iron chelation therapy are necessary for transfusion-dependent thalassemia patients. While some patients show a reduction in SF levels after 3 years of treatment, there are still individuals who exhibit elevated levels necessitating ongoing management.

Analysis of Thalassemia Gene Mutation Types and Ethnic Distribution Characteristics in Hechi Area, Guangxi

To investigate the genotype, mutation type, and ethnic distribution characteristics of thalassemia in the population of Hechi area, Guangxi, and to provide a reference basis for prevention and control of thalassemia and eugenic counseling in the region. Gap-polymerase chain reaction (gap-PCR) and reverse dot blot (RDB) were used for genetic testing on suspected thalassemia persons, and the results were analyzed. Among 29 136 samples, a total of 17 016 (58.40%) positive samples for thalassemia genes were detected, with a higher detection rate in males than in females (χ2=49.917，P < 0.001). The detection rates of thalassemia genes were significant different among Zhuang, Han, Yao, Mulao, and Maonan ethnic groups (χ2=546.121, P < 0.001). The α-thalassemia genotypes were mainly --SEA /αα (16.67%), -α3.7/αα (8.90%), α CSα/αα (6.00%). Additionally, four rare genotypes were detected, including -- THAI/αα (47 cases), HKαα/αα (2 cases), --SEA /-α 21.9 (2 cases), and -- THAI/αCSα (1 case). The β-thalassemia genotypes were mainly β CD17/βN (7.49%), βCD41-42/βN (6.70%), βCD71-72/βN (0.44%). 108 cases of moderate and severe β-thalassemia were detected, of which 81 cases had a history of blood transfusion, the transfusion frequency of 60 cases was more than 10 times/year, and 10 cases received bone marrow transplantation. Thalassemia in Hechi area is predominantly deletion type --SEA /αα, the detection rate of thalassemia in ethnic minorities is higher than that in Han population. In this area, moderate and severe β-thalassemia have certain incidence, these patients mostly need regular blood transfusion and iron removal treatment, and very few patients have received bone marrow transplantation. This study provides a certain reference basis for prevention and control of thalassemia and eugenic counseling in the region.

Comparison of Yearly Cost Related to Complications Between Deferasirox and Deferiprone Monotherapy in Thalassemia.

Hemoglobin disorders such as thalassemia major have created an economic burden on the health care system. Iron chelation therapy (ICT) is the most expensive cost component in patients with thalassemia. ICT was administered to reduce the toxic effects of iron overload. This study aims to compare the costs of iron chelators as monotherapy in patients with thalassemia major in Indonesia, specifically in Cipto Faculty of Medicine, Universit. This is a retrospective analytical observational study. Data were collected from the thalassemia registry from 2016 to 2019. Patients' age, gender, type of thalassemia, and type of iron chelation were recorded. Complications and total annual costs were evaluated. All thalassemia patients aged ≥2 years who were only receiving monotherapy ICT and had no history of therapy switching were eligible. We excluded subjects who moved out to other facilities or lost to follow-up. From a total of 256 subjects, 249 subjects were included. The median age is 28 years old. Both sexes were represented equally. As many as 96.8% of subjects have thalassemia beta. Deferiprone was the most common iron chelator used (86.7%). Complications were observed in the subjects based on 4-year data collection; most of them were cardiomyopathy, diabetes mellitus, delayed puberty, and malnutrition ( P =0.422; P =0.867; P =0.004; and P =0.125, respectively). Deferiprone had a lower mean annual cost of USD 3581 than deferasirox, which had a cost of USD 6004. Cardiomyopathy, diabetes mellitus, delayed puberty, and malnutrition were the most common complications found in the study. This study showed that deferiprone should be taken as consideration as a drug of choice to treat iron overload in thalassemia provided by Indonesian national health insurance which is less costly despite the probability of complications found after the treatment was given. Further investigations are required to evaluate contributing factors of complications in thalassemia.

Thalassemia Genotypes and HbA2 levels of Children in Wuzhou, Guangxi

To analyze thalassemia genotypes and distribution of children in Wuzhou Guangxi, and evaluate the diagnostic value of HbA2 in children's thalassemia screening, so as to provide scientific evidence for the prevention and control strategies of thalassemia. Four hundred and fifty-eight children suspected with thalassemia in Wuzhou were enrolled from March 2017 to June 2022. The level of HbA2 was detected using Bio-Rad VARIANT II Hb analysis system. The deletion of α-thalassemia was measured with gap-PCR assay, and the point mutation of α- and β-thalassemia was tested with DNA reverse dot blot hybridization assay. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of HbA2 for children's thalassemia. A total of 304 thalassemia carriers were detected in 458 children, accounting for 66.38%. One hundred and seventy-five cases were defined to be α-thalassemia, with the main type of --SEA/αα (54.86%). Thirty-six cases were defined to be intermediate α-thalassemia, with the main type of -α3.7/--SEA (9.72%). In 108 cases with β-thalassemia, βCD41-42/βN was the main type, accounting for 49.07%, followed by βIVS-Ⅱ-654 /βN (14.81%). Seven cases were moderate/severe β-thalassemia (predominantly β-28/β-28 and βCD41-42/βCD17/). Twenty-one genotypes of α- and β-thalassemia were found in the children. There was significant difference of HbA2 level between the children with different types of thalassemia and healthy controls (all P < 0.001). ROC curve analysis showed that the sensitivities of HbA2 for α-thalassemia, β-thalassemia and αβ-thalassemia were 74.3%, 82.4% and 85.7%, with the optimal cut-off values of 2.60%, 3.60% and 3.70%, respectively, the specificities were 64.3%, 96.1% and 96.8%, and the area under the curve were 0.690, 0.887 and 0.916, respectively. The thalassemia genotypes of children in Wuzhou are diverse. It is necessary to further strengthen the prevention and control measure of thalassemia to reduce birth defects and improve birth quality.

Analysis of the Gene Mutation Type and Frequency of Thalassemia Patients in Jingzhou Area

To analyze the gene mutation types and frequence of thalassemia patients in Jingzhou area. A total of 721 suspected thalassemia patients who were visited in Jingzhou Central Hospital from June 2019 to June 2022 were selected as the research objects. There were 204 males and 517 females. PCR-reverse dot hybridization method was used to analyze the types and frequencies of 23 common α or β thalassemia gene mutations. Among the 721 patients with suspected thalassemia, 228 cases were positive for α or β thalassemia gene, with a total positive rate of 31.62%, including 87 cases of α-thalassemia, accounting for 38.16%, and 140 cases of β-thalassemia, accounting for 61.40%. There was 1 case of α β complex thalassemia, accounting for 0.44%. A total of 4 types of α-thalassemia gene mutations were detected, all of which were deletion types, including αα/--SEA (64/87, 73.56%), αα/-α3.7 (14/87, 16.09%), --SEA /-α3.7 (7/87, 8.05%), αα/-α4.2 (2/87, 2.30%). Among 140 patients with β-thalassemia, 138 were pure heterozygotes, and the genotypes of IVS-II-654M (63/140, 45.00%), CD41-42M (34/140, 24.29%), CD17M (18/140, 12.86%) and CD27-28M (10/140, 7.14%) accounted for 89.29% of all mutations (125/140), 2 cases of double heterozygosity (2/140, 1.43%) were found, no homozygous β-thalassemia were detected; 1 case of αβ complex thalassemia with genotype -α3.7/IVS-II-654M was found. The incidence of difference types of thalassemia was statistically significant (χ2=194.250, P < 0.001). The percentage of positive thalassemia genes was not significantly difference between male and female suspected patients (χ2=0.199, P =0.655). The α-thalassemia gene mutation in Jingzhou area is dominated by αα/--SEA, and the IVS-II-654M mutation is more common in β-thalassemia, and α β complex thalassemia is relatively rare, which can provide a reference for the formulation of prevention and treatment measures for thalassemia in Jingzhou area.

Screening and Diagnosis of Rare Thalassemia Variants: Is Third-Generation Sequencing Enough?

Rare thalassemia subtypes are often undiagnosed because conventional testing methods can only identify 23 common types of α- and β-thalassemia. To assess a comprehensive approach for the screening and diagnosis of rare thalassemia. The study cohort included 72 individuals with suspected rare thalassemia variants. Screening was conducted by next-generation sequencing (NGS) combined with third-generation sequencing (TGS) and chromosomal microarray analysis (CMA)/copy number variation sequencing. Of the 72 individuals with suspected rare thalassemia, 49 had rare α- or β-gene variants. NGS combined with gap polymerase chain reaction detected a total of 42 cases, resulting in a positive detection rate of 58.3%. Additionally, 4 α-globin genetic deletions were identified by TGS, which increased the variant detection rate by 5.6%. Two samples with a microdeletion of chromosome 16 or 11 were detected by CMA, which increased the detection rate by 2.8%. For one sample, reanalysis of the NGS and TGS data confirmed the presence of the β41-42/βN and βN/βN mosaic. The HBB:c.315 + 2delT mutation was initially reported in Guangdong Province, China. Two HBB gene mutations (HBB:c.315 + 5G>C and HBB:c.295G>A) and 4 rare HBA gene deletions (-11.1, -α27.6, -α2.4, and -α21.9) were initially identified in the Zhonshan region. The hematologic phenotypes of all rare cases in this study were clarified. Rare thalassemia variants are more common than previously thought. Despite advancements in TGS, there is still no foolproof method for detection of all types of thalassemia. Thus, a comprehensive approach is necessary for accurate screening and diagnosis of rare thalassemia variants.

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.

Study of Alloimmunization in Transfusion-dependent Thalassemia Patients at a Tertiary Care Hospital

Abstract: BACKGROUND: Alloantibodies against donor red blood cells (RBCs) are developed by patients with transfusion-dependent thalassemia (TDT), which causes the donor RBCs to hemolyze. This decreases the transfusion’s efficacy and increases the risk of adverse effects like iron overload. MATERIALS AND METHODS: Two hundred and five TDT patients with an average age of 11 ± 6 years enrolled in this study underwent the Direct Coombs Test (DCT) to determine the frequency of alloimmunization. RESULTS: Most cases were of thalassemia major (TM) (76.09%), followed by thalassemia intermedia (TI) and (21.95%). Most of the cases were diagnosed and started on regular blood transfusion therapy between the ages of 1 and 10 years. Majority of the cases were born of parental consanguinity. Only 13.17% of the patients underwent splenectomy, of which TM cases were the majority. Even though O-positive was the most frequent blood type, most of the operated and alloimmunized cases belonged to the B-positive blood type. Only 10.24% of the patients had alloimmunization, with 51.85% of them developing it after splenectomy. Among all study participants, no correlation was found between the blood group and the type of thalassemia, alloimmunization, or splenectomy. Among TDT cases, there was a significant correlation (P &lt; 0.0001) between alloimmunization and splenectomy. Alloimmunization and splenectomy correlated significantly with the total number of transfusions, the volume of blood transfused, and the transfusion initiation age. CONCLUSION: Our findings emphasize the significance of antigen typing in TDT patients before the first transfusion.

Prevalence of various types of anemia and thalassemia in pregnant women: experience from Northern India

Prevalence of various types of anemia and thalassemia in pregnant women: experience from Northern India

Blood Indices of the Patients with β-Thalassemia Minor Compared to the Patients with β-Thalassemia Minor-Alpha-Thalassemia

Objective: Thalassemia, as one of the most common genetic diseases, is a group of hereditary hemoglobin disorders due to a slight disturbance in the production of alpha and beta globin chains in the structure of hemoglobin occurs. There are still no clear criteria for differentiating thalassemia types based on hematological findings. In the current study, we aimed to evaluate the low-grade beta-thalassemia (β-thalassemia) indices in comparison with β-thalassemia minor with alpha-thalassemia (α-thalassemia).&#x0D; Methods and materials: In this descriptive-analytic study, 120 patients were enrolled, including 80 patients with minor β-thalassemia and 40 patients with minor β-thalassemia with α-thalassemia. Of all patients, 5cc blood samples were taken. The red blood cell parameters including mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and hemoglobin were determined. The level of MCV&gt; 80 and A2&gt; 3.5 β-thalassemia minor and MCV &lt;80 and A2 &lt;3.5 were considered as elevated thalassemia or iron deficiency anemia.&#x0D; Results: The results showed that the mean of hemoglobin, HCT, MCH, MCHC, and MCV in the β-thalassemia group was significantly lower than that of the β-thalassemia with α-thalassemia group (P &lt;0.0001). On the other hand, the level of these indices in the control group was significantly higher than in the two groups of patients (P&lt;0.0001). The results showed that the percentage of hemoglobin A2 in the β-alpha-thalassemia group was 4.5 ± 0.91, significantly higher than the β-thalassemia group. The rate of hemoglobin and MCV was significantly lower in the β-thalassemia group compared to the silent and trait β+αthalassemia group. Also, the rate of hematocrit was significantly lower in the β-thalassemia group compared to the trait, although had no significant difference with the silence group.&#x0D; Conclusion: Based on our findings, despite the difference between some hematocrit indices in the patients with β-thalassemia and β-αthalassemia, these indices cannot be used as differential indices.

Predicting factors of survival rates among alpha- and beta-thalassemia patients: a retrospective 10-year data analysis

BackgroundThalassemia is a genetic hemoglobinopathy in which a defective globin chain can cause transfusion-dependent anemia and other complications. As genotype interactions lead to variations in the clinical course among patients with thalassemia, clinical factors may help predict survival in the types of thalassemia complicated by gene interactions.AimThis study aimed to determine the clinical factors associated with survival in patients with thalassemia. We retrospectively reviewed the medical records of patients with thalassemia older than 15 years between 2002 and 2020 that were available at the Rajavithi Hospital. Data on the clinical parameters, laboratory tests, treatments, and survival status were collected and analyzed.ResultsOf the 478 thalassemia patients included, 68.8% were women, and the mean age was 41 ± 17 years. The most common type of thalassemia was β-thalassemia (53.3%). Male sex, low body mass index, the thalassemia type, comorbidities, low hemoglobin level, high ferritin level, and regular blood transfusion were significantly associated with short-term survival. However, only the thalassemia type (β-thalassemia, p = 0.048) and the co-inheritance of the α- and β-thalassemia genotypes (p = 0.03) were independently associated with death. The overall survival rates among patients with α-thalassemia, β-thalassemia, and co-inheritance of the α- and β-thalassemia genotypes were 98.1%, 90.6%, and 75.0%, respectively. The death rate was 6.3%, and the most common cause of death was infection.ConclusionThe thalassemia genotype was a predictive factor of survival, and co-inheritance of the α- and β-thalassemia genotypes results in a shorter-term survival compared with other types, especially transfusion-dependent thalassemia. These results can be applied in clinical settings to predict and possibly extend the life expectancy of patients with thalassemia.

Misdiagnosis of β-Thalassemia Major Due to Chinese Gγ+(Aγδβ)0-Thalassemia Combined with β0-Thalassemia

δβ-thalassemia is a rare type of thalassemia characterized by increased Hb F levels, including mainly Chinese Gγ(Aγδβ)0-thalassemia, Yunnanese Gγ(Aγδβ)0-thalassemia, Cantonese Gγ(Aγδβ)0-thalassemia in China. Due to the low rate of δβ-thalassemia carriers, there are few reports of δβ-thalassemia combined with β-thalassemia causing β-thalassemia major. Herein, we described the combination of Chinese Gγ(Aγδβ)0-thalassemia and β-thalassemia leading to β-thalassemia major in a Chinese patient. Hemoglobin analysis was performed by capillary electrophoresis (CE). Routine genetic analysis was carried out by gap-polymerase chain reaction (Gap-PCR) and PCR and reverse dot blot (PCR-RDB). Multiple ligation-dependent probe amplification (MLPA) was used to detect the large deletion, and Gap-PCR confirmed the deletion. A CE result showed an elevated Hb F level of 98.7% and 11.7% in the proband and her mother, but the proband was diagnosed with βCD17M/βCD17M using routine genetic analysis. However, her father was heterozygous for CD17 in β-globin, and her mother was detected as SEA heterozygous. The further analysis presented that the proband had actually missed the diagnosis of Chinese Gγ(Aγδβ)0-thalassemia by MLPA and PCR-RDB. Finally, the genotype of the proband was corrected from βCD17M/βCD17M to βCD17M/βGγ(Aγδβ)0. This is the first report of Chinese Gγ(Aγδβ)0-thalassemia combined with β-thalassemia resulting in β-thalassemia major in China. Screening for δβ-thalassemia by Hb analysis could be an effective method.

Clinical Insights: Prevalence of β-Thalassemia Mutations (IVSI-5, FSC8/9, and CD41/42) in the Swat District

Background: Thalassemia is a prevalent condition characterized by decreased production or absence of hemoglobin globin chains. There are 2 types of thalassemia, alpha thalassemia and beta thalassemia (β-thalassemia), classified according to defects in the alpha or beta protein chain. β-Thalassemia results from a diverse range of mutations in the β subunit of the hemoglobin gene (HBB). This results in severe reductions in erythrocyte and hemoglobin levels. Worldwide, more than 40,000 babies are born with β-thalassemia annually. There are approximately 80 million β-thalassemia carriers. In Pakistan, the annual birth rate of β-thalassemia major carriers is approximately 6,000, and 50,000 to 100,000 patients suffer from this common inherited disorder. IVSI-1, IVSI-5 (G&gt;C), Fr 8/9 (+G), Fr 41/42 (-TTCT), and del 619 are the 5 most common mutations that account for 90% of β-thalassemia cases in Pakistan. This study aimed to investigate the prevalence of β-thalassemia mutations (IVSI-5, Fr 41/42, and Fr 8/9) in the Swat district and to analyze the blood morphology of different mutant thalassemia blood samples. Methods: A cross-sectional study was performed at the Forensic Research Lab University of Swat from December 2021 to March 2022. The study included a total of 150 blood samples. Comparative analysis of blood morphology through microscopy was carried out on samples from patients with different β-thalassemia mutations and normal individuals. Genomic DNA extraction was performed according to the Sambrook protocol, and DNA was quantified via agarose gel electrophoresis. Thalassemia mutations were detected by amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR). The frequencies of different β-thalassemia mutations were analyzed. Results: Thalassemia blood cells were more hypochromic and microcytic than normal blood cells, although no differences were detected in the morphology of IVSI-5, Fr 8/9, or CD41/42 mutant blood cells. The IVSI-5, Fr 8/9, and CD41/42 mutations were analyzed through agarose gel electrophoresis of the ARMS-PCR data. The IVSI-5 mutation was the most prevalent mutation, identified in 52.2% (78/150) of the patients. The prevalence of Fr 8/9 and CD41/42 mutations was 22.6% (34/150) and 18.6% (28/150), respectively. A total of 5.33% (8/150) of patients had double mutations, and only 1 patient (0.666%) had all 3 mutations. Conclusion: This study provides a reliable reference for the detection of different mutations in β-thalassemia and will help to formulate different strategies for improving the awareness of the general public. For a more thorough analysis of common β-thalassemia mutations, the investigation should be extended to more ethnic regions of Pakistan.

Thalassemia (Beta-Thalassemia)

Thalassemia is an inherited blood disorder characterized by less oxygen carrying protein (Haemoglobin) and fever red blood cells in the body than normal. There are mainly two types of thalassemia i.e. Alpha and Beta thalassemia about 1-5% of the global population 80-90 million people are the carrier of ß thalassemia which is major concern. In this review article fundamental aspects about thalassemia, it’s history is discussed. This review also focuses upon the types of ß thalassemia, pathophysiology, mechanism of transmission, diagnosis of ß thalassemia . Finally various treatment strategies and future aspects are addressed.

Association of Hemoglobin Levels with Healthcare Resource Utilization and Costs in Non-Transfusion-Dependent α- and β-Thalassemia: A Retrospective Observational Study Using Real-World Data

Introduction: Alpha (α)- and beta (β)-thalassemia result from reduced synthesis of α- or β-globin, respectively, leading to ineffective erythropoiesis, chronic hemolytic anemia (HA), and related complications. Thalassemia can also be characterized phenotypically as transfusion-dependent thalassemia (TDT) or non-transfusion-dependent thalassemia (NTDT). Decrease in hemoglobin (Hb) has been linked to increased risk of comorbidities and number of comorbidities in NTD β-thalassemia. Healthcare resource utilization (HCRU) has been analyzed in TDT in the US, but there is limited research on the association of Hb levels with HCRU and costs in α- and β-NTDT. Objective: To assess the association of average Hb levels with HCRU and costs in adult patients with α- and β-NTDT using retrospective claims data. Methods: This study analyzed data from the Merative ® MarketScan ® Commercial, Medicare, and Lab Results Databases for patients with thalassemia and no evidence of other HAs who were ≥18 years of age on the index date (date of the first observed diagnosis code for α- or β-thalassemia). Patients were stratified by type of thalassemia (α- or β-thalassemia) and by transfusion dependence (NTDT or TDT). NTDT was defined as &amp;lt;8 transfusions within 12 months of follow-up or with &amp;gt;42 days between any 2 adjacent transfusions. To evaluate if the results in NTDT were driven by patients with β-NTDT, patients with α-NTDT were also analyzed separately. Hb levels, HCRU (inpatient [IP] admissions, outpatient [OP] visits, and emergency room [ER] visits), and costs were assessed during a variable-length follow-up period (at least 12 months from the index date to end of plan enrollment, end of study, or IP death, whichever occurred first). Available Hb levels were averaged across the follow-up period for each patient. HCRU (number and type of service) and costs (US dollars) were converted to per-patient per-year values. All dollar estimates were inflated to 2020 (using Medical Care Component of Consumer Price Index). To assess the association of Hb levels with HCRU and cost outcomes, univariate regression analyses with negative binomial models were conducted. Percent changes in cost and incidence rate ratios of HCRU associated with 1 g/dL decrease in Hb level and corresponding 95% confidence intervals and p values (with significance level set to 0.05) were reported. Results: In the Commercial/Medicare database, 4077 adult patients with thalassemia and a variable length follow-up of at least 12 months were identified (median length of follow-up: 943 days). Of these, 909/4077 (22.3%) had at least 1 Hb value during the follow-up period in the Lab Results database, including 400 patients (44.0%) with α-thalassemia, 509 (56.6%) with β-thalassemia, 898 (98.8%) with NTDT (α or β), and 11 (1.2%) with TDT (α or β). The average Hb value per patient with NTDT (α and β; N=898) was 11.3 g/dL (11.5 g/dL for α-NTDT; N=400). In the NTDT group, 4.1% had at least 1 transfusion in first 12 months of follow up (3.6% had 1-3 transfusions and 0.5% had 4-7). For all patients with NTDT, with each 1 g/dL decrease in Hb, the number of IP admissions increased by 17%, OP visits by 8%, and ER visits by 11% (all p&amp;lt;0.001). For patients with α-NTDT, with each 1 g/dL decrease in Hb, the number of IP admissions increased by 15%, OP visits by 6%, and ER visits by 16% (all p&amp;lt;0.01; Table 1). Regarding costs for all patients with NTDT, with each 1 g/dL decrease in Hb, total healthcare costs increased by 15% (p&amp;lt;0.001), IP costs by 56% (p&amp;lt;0.001), OP costs by 12% (p&amp;lt;0.001), ER costs by 20% (p&amp;lt;0.003), and prescription costs by 12% (p=0.061). For patients with α-NTDT, with each 1 g/dL decrease in Hb, total healthcare costs increased by 14% (p&amp;lt;0.001), IP costs by 47% (p&amp;lt;0.001), OP costs by 10% (p&amp;lt;0.001), ER costs by 30% (p&amp;lt;0.003), and prescription costs by 9% (p=0.322). It is possible that because of incorrect/incomplete coding, some patients with thalassemia minor may have been included in the analyses, which may account for the higher-than-expected Hb levels in the NTDT cohorts. This may, in turn, underestimate the impact of Hb level on HCRU and costs. Conclusion: In this study, each 1 g/dL decrease in Hb was associated with significantly higher HCRU and costs. This association was seen in both the NTDT group and α-NTDT subgroup suggesting that both α-NTDT and β-NTDT experience this burden. This analysis indicates that raising Hb levels in patients with both α- and β-NTDT could result in reduced HCRU and costs.

Impact of COVID-19 in Thalassemia Patients Undergoing Hematopoietic Stem Cell Transplant Recipients

Objective: This article primarily examines the clinical attributes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in transplant recipients with thalassemia, offering significant insights into the treatment and care of this patient population. Method: The present study retrospectively analyzed the data of all thalassemia patients who underwent Hematopoietic stem cell transplantation (HSCT) at the First Affiliated Hospital of Guangxi Medical University between December 2019 and December 2022. A total of 280 patients were included, of which 81 had confirmed coronavirus disease 2019 (COVID-19). The study collected information on patient demographics, transplantation type and timing, graft-versus-host disease (GVHD), use of immunosuppressive agents, onset time and severity of COVID-19, and prognosis. Follow-up was conducted until March 31, 2023.Univariate analysis was performed using SPSS v25.0, and GraphPad Prism was used for the cumulative incidence comparisons. Results: The median age was 3.6(2-19) years.The main type of thalassemia was β type (93.9%). Identical sibling donors accounted for 40%, haploidentical donors accounted for 25.4%, and identical unrelated donors accounted for 34.6% (10/10). The main source of hematopoietic stem cells was bone marrow combined with peripheral blood (85%).There were no significant differences in age, gender, diagnosis, donor type, graft type, use of immunosuppressive agents, GVHD, and pneumonia of pro-COVID-19 between infected patients and non-infected patients with SARS-CoV-2. Most of the patients were mild (74 cases, 91.3%) in terms of the severity of COVID-19 infection, only 8.6% of the moderate cases, and none severe and died. 74 cases were cured without drug treatment. Of the seven patients treated with medications, four were azvudine and three were nematasvir. The median number of days (IQR) of treatment for COVID-19 was 5(5) days. The cumulative incidence in the immunosuppressive group was higher than that in the non-immunosuppressive group over the same time frame. There was no significant difference in the final infection rate of COVID-19 among patients receiving transplantation in different years(2020,2021,2022), which was 24.7 26.8 36.5 ( p=0.368), respectively. Conclusion: The low infection rate and no severe cases may be due to scientific protection and timely medication. There are no special risk factors for COVID-19 infection in thalassemia patients after transplantation.

Cutaneous Manifestations in Adult Thalassemia Patients

Background: A wide range of cutaneous manifestations have been described in thalassemia patients. No studies have been conducted in Southeast Asia where there is a high prevalence of hemoglobin E (Hb E) thalassemia. Objective: The primary objectives of the present study were to determine the prevalence of cutaneous manifestations among adult thalassemia patients and assess how cutaneous findings differ between patients with and without β-thalassemia (β-thal)/Hb E. Secondary objectives were to determine any associations between cutaneous manifestations and clinical or laboratory findings and to evaluate quality of life (QoL). Materials and Methods: The present study was a cross-sectional descriptive study conducted between April 2021 and December 2022 in Thailand. Adults aged 18 years and older with any type of thalassemia were eligible. The authors collected relevant demographic data, cutaneous and laboratory findings, as well as responses to a validated Thai version of the Dermatology Life Quality Index (DLQI). Results: One hundred patients (37% male) were included, with a median age of 33 (IQR of 24, 41) years. Of these, 76% had β-thal/Hb E. Xerosis was the most common cutaneous manifestation at 69%. Hyperpigmentation was more common in patients with β-thal/Hb E than those without at 41% versus 17% (p=0.031). Extramedullary erythropoiesis, xerosis, and serum ferritin were significantly associated with hyperpigmentation. The overall median DLQI score was 0 (IQR 0, 2). Conclusion: Xerosis was the most common cutaneous findings in adult thalassemia patients, and hyperpigmentation was more common in patients with β-thal/Hb E. However, cutaneous changes had low impact on patients’ QoL. Keywords: Thalassemia; Cutaneous manifestations; Hemoglobin E thalassemia

Assessment of Iron Chelation Therapy Adherence in Patients with Thalassemia Major in Babylon Province

Abstract BACKGROUND: Thalassemia is severe public health problem in Iraq and other nearby countries, represents about 75% of all hemogloniopathy with prevalence and incidence 36/100.000 and 34/100.000 respectively. beta thalassemia major represented 67% of all types of thalassemia. In the absence of treatment, it cause bony deformities and hepatosplenomegaly. Bone marrow transplant is the only curative treatment, but it is restricted to only a few patients. As a result, the majority of patients also receive iron chelation therapy along with routine blood transfusions. Failure of chelation can result in endocrinopathies, cardiomyopathy, and hepatic failure, iron chelation therapy requires careful monitoring and high adherence to obtain acceptable therapeutic outcomes. The main factor causing morbidity and mortality in thalassemia is iron excess. Adherence is a complicated phenomenon that involves interconnected elements linked to each patient’s condition, therapy, and environment as well as psychological elements. OBJECTIVE: We assessed the adherence to iron chelation therapy in thalassemia major patients in Babylon province in Iraq and trying to identify the factors leading to poor adherence. MATERIALS AND METHODS: This is cross sectional study performed over the course of two months on 100 patients with β-thalassemia major registered at hereditary blood disease center, in Babylon, Iraq, using deferasirox as chelation agent by direct interview using a predesigned questionnaire. RESULT: Mean age was (14.93± 6.85) years, (61%) of patients were males. The great majority (97%) were single. (59%) of patients were below bachelor. (96%) were unemployed and about half of patients (51%) were rural. Number of affected family members range from 0 to 4, with only one affected member rank one. (92%) of them not use chronic medication other than chelating therapy and folic acid. Disease complication other than organomegaly present in 14% of patients, that include hepatitis C infection, delayed growth, diabetes mellitus and hypothyroidism. More than three-quarters of patients (79%) have good adherence for chelation therapy, were 21 patients have poor adherence, mostly secondary to gastrointestinal side effect (nausea, vomiting, stomach discomfort and bitter taste), or non-specific causes (disinterest, forgetfulness, feeling hassled and taking other medication). The mean duration from diagnosis was 13.6 years, transfusion duration was 13.4 years, transfusion frequency was about 23 days and chelating duration was 10.7 years. Mean of packed cell volume (PCV) was 22%, while mean of serum ferritin was 4342mg/ dl. There was significant association between mean PCV of patients and their adherence to chelating therapy P value was (0.009), other variable show non-significant association. CONCLUSION: Thalassemia major patients in Babylon governorate have good level of adherence to iron chelation therapy which was nearly comparable or even better than adherence rates in other Middle East countries. Despite that, the chelation is inadequate due to logistic issues.