Thalassemia Screening Program Research Articles

Rising Cases of Hb H Disease in Iraq Highlight the Urgent Need for Pre-Pregnancy Screening

General background: Hemoglobin H (Hb H) disease results from mutations in three of the four α-globin genes, leading to α-thalassemia. Specific background: In Iraq, this condition is rare among alpha-thalassemia cases. The disease presents significant hematological abnormalities, impacting quality of life. Knowledge gap: Despite its rarity, few studies have characterized the hematopathological features and prevalence of Hb H disease in specific Iraqi regions. Aims: This study aimed to assess the hematological parameters and prevalence of Hb H disease among patients in Diyala province, Iraq. Results: A total of 81 patients with Hb H disease (53.18% male, 46.91% female) were registered at the Baqubah Teaching Hospital in 2023. Median patient age was 21.8 years (range 4-48). Hematological analysis revealed consistently low levels of hemoglobin (Hb) and hematocrit (HCT) compared to standard values. Mean corpuscular volume (MCV) was also significantly reduced, with 58.02% of patients presenting Hb levels below 10 g/dL. The 21-40 age group had the highest incidence (46.91%). Novelty: This study is among the few to investigate Hb H disease prevalence and hematopathological characteristics in Diyala province, revealing an unexpectedly high incidence in the 21-40 age group. Implications: These findings suggest that hematological parameters, including MCV and Hb levels, should be considered in thalassemia screening programs, particularly in pre-pregnancy assessments, to prevent the birth of children with severe forms of alpha-thalassemia and reduce Hb H disease prevalence. Highlights: Hb H disease shows low hemoglobin and MCV abnormalities. Highest incidence occurs in patients aged 21-40 years. Pre-pregnancy screening reduces severe alpha-thalassemia risk. Keywords: Hb H disease, alpha-thalassemia, hematological parameters, Diyala province, prevalence

Detection of Hemoglobin Constant Spring: A Comparison of Capillary Electrophoresis Versus High-Performance Liquid Chromatography.

In Malaysia, Hemoglobin Constant Spring (Hb CS) is the most common non-deletional α-thalassemia, caused by a mutation at the termination codon of the α2-globin gene (TAA>CAA). Detection typically involves identifying an abnormal peak at zone 2 on capillary electrophoresis (CE) or a small peak at the C-window on high-performance liquid chromatography (HPLC), indicative of Hb CS. This study aimed to investigate the correlation between HPLC and CE in detecting Hb CS, evaluating their respective diagnostic accuracies and limitations. A cross-sectional study was conducted at Hospital Sultanah Nur Zahirah involving secondary school students (Form 4) from Terengganu who participated in a thalassemia screening program conducted by the Ministry of Health (MOH) from January 2019 to December 2022. Blood samples from subjects showing a positive peak in zone 2 of CE and a small peak at the C-window of HPLC were selected. Molecular studies of these samples were performed to confirm the presence of Hb CS. For the statistical analysis, the Pearson correlation coefficient was employed to assess the relationship between CEand HPLCresults. Hb CS was confirmed in all samples by molecular studies, revealing 92.3% heterozygous, 7.2% compound heterozygous, and 0.5% homozygous cases. CE detected 92.3% of heterozygous Hb CS cases, while HPLC detected only 48.2%. For compound heterozygous Hb CS, CE detected 100%, whereas HPLC detected 89.3%. Both homozygous cases were detected by CE and HPLC. The Pearson correlation coefficient test showed a significant linear relationship (p<0.001) between CE's zone 2 peak values and HPLC's C-window peaks (n=389). Conclusion: These findings highlight the efficacy of CE as a reliable method for Hb CS detection, suggesting its potential superiority over traditional HPLC in clinical settings.

Low-Cost Automated Microscopy and Morphology-Based Machine Learning Classification of Sickle Cell Disease and Beta-Thalassemia in Nepal and Canada

INTRODUCTION Sickle cell disease (SCD) is the most common inherited blood disorder, and is associated with a high mortality rate for children in low-resource settings, where the disease burden is high. Early screening and treatment options reduce morbidity and mortality. In addition to screening for SCD, screening for asymptomatic, heterozygous conditions, such as sickle cell trait (SCT) and β-thalassemia trait, is required for effective SCD and thalassemia screening programs. However, rural and remote communities lack accurate low-cost screening techniques. The goal of this study is to augment a common low-cost screening test, the sickling test, using automated microscopy and machine learning to classify individuals with SCD (HbS/β-thalassemia and HbSS), trait conditions (HbAS and HbA/β-thalassemia), and those without common beta-globin disorders (HbAA) for implementation in Nepal. As HbC mutation is not encountered in Nepal, screening for HbSC or HbAC was not included. Additionally, we aim to evaluate the feasibility of 5 low-cost techniques to supplement/replace the local gold standard test (Hb HPLC), which is inaccessible in rural/remote settings. METHODS In this study (ClinicalTrials.gov Identifier: NCT05506358), blood samples were collected and tested at respective clinical sites in Nepal (Mount Sagarmatha Polyclinic and Diagnostic Center, Nepalgunj) and Canada (St. Paul's Hospital and BC Children's Hospital, Vancouver). Participants (138 total: 111 Nepal; 27 Canada) between ages 2 to 74 whose diagnoses were previously established by Hb HPLC were recruited. Five low-cost tests (our augmented sickling test, HbS solubility test, HemoTypeSC, Sickle SCAN, Gazelle Hb variant test) and Hb HPLC were performed on all participants (30 HbAA; 23 HbA/β-thalassemia; 45 HbAS; 11 HbS/β-thalassemia; 29 HbSS). Informed consent was provided by the participants or parents, according to protocols approved by institutional/national research ethics boards. For the sickling test, a sealed wet preparation of blood mixed with 2% sodium metabisulphite was imaged with a robotic microscope (Octopi) with automated scanning/focusing. The images of blood cells were segmented using Cellpose 2.0, allowing for morphological characterization of cells and morphology based classification, with an 80:20 participant-wise split of training and testing data. RESULTS Using high-throughput imaging, more than 300,000 de-identified images of blood films were collected, resulting in more than 1.5 trillion segmented cells. The de-identified images and processed data will be released in an open-access data repository. The frequency distribution of 11 different morphological parameters were used for machine learning based classification, resulting in testing sensitivity and specificity of 82.9% and 82.4%, respectively. The confusion matrix (Figure 1) shows that sensitivity of detecting SCD cases (HbS/β-thalassemia and HbSS) was 98.6%, and most misclassifications were between trait and normal conditions. Comparing the different low-cost techniques (Table 1), the Gazelle Hb variant test had the highest sensitivity and specificity (97.0% and 99.3%), but is more than twice as expensive than the augmented sickling test, while lateral flow assays (HemoTypeSC and SickleSCAN) had lower sensitivity (74-75%) than the augmented sickling test, due to their inability to detect β-thalassemia trait. CONCLUSIONS The sickling test, which is traditionally unable to distinguish between SCT and SCD, was augmented to detect SCD and trait conditions (including β-thalassemia) with an overall sensitivity of 82.4% (98.6% sensitivity for SCD detection). The preliminary results indicate that image-based classification can be a promising low-cost and automated screening tool for low-resource settings, reducing the need for highly-trained personnel for device operation and disease detection. Furthermore, the open-access image dataset can be used to improve classification in the future, as segmentation/classification algorithms improve over time.

USE OF PYTHON AND COMPLETE BLOOD COUNT PARAMETERS FOR COST-EFFECTIVE THALASSEMIA SCREENING IN RESOURCE-LIMITED SETTINGS: DEVELOPMENT AND VALIDATION OF A SCREENING PROGRAM.

Thalassemia screening is typically done using High-performance liquid chromatography (HPLC), which is an accurate but expensive method that is not widely available. To overcome this issue, researchers have looked into alternative screening methods, such as using erythrocytic indices obtained from a complete blood count (CBC) test. This approach has proven to be highly sensitive and specific, making it an attractive and cost-effective solution for excluding normal populations from thalassemia screening programs. Consequently, it has the potential to improve the efficiency of screening programs, particularly in settings with limited resources.&#x0D; A Python program, using the study by Samanta et al. (2021) as a basis, to screen for thalassemia using CBC parameters was created. The program was developed in Python 3.8 using Spyder IDE (Integrated development environment), and it takes in CBC parameters, such as hemoglobin, RBC (Red blood Corpuscles), MCV (mean corpuscular volume), MCH (Mean corpuscular hemoglobin), and HCT (Hematocrit), to determine an individual's thalassemia status. We validated the program using a dataset of 3,000 students who had undergone CBC testing at a local clinic. The dataset was anonymized to ensure privacy protection&#x0D; Our study showed that the Python program for thalassemia screening based on CBC parameters accurately identified individuals with thalassemia. We validated its performance on a large dataset of students and found that it has the potential to improve screening efficiency and accuracy, particularly in resource-limited settings. However, additional validation studies are necessary to confirm its generalizability and usefulness in diverse populations.

Application of real-time PCR-based multicolor melting curve with automatic analysis system in pregestational and prenatal thalassemia diagnoses.

To evaluate the value of the real-time PCR-based multicolor melting curve analysis (MMCA) with an automatic analysis system used in a mass thalassemia screening and prenatal diagnosis program. A total of 18,912 peripheral blood samples from 9456 couples and 1150 prenatal samples were detected by MMCA assay. All prenatal samples were also tested by a conventional method. Samples with unknown melting peaks, unusual peak height ratios between a wild allele and a mutant allele, or a discordant phenotype-genotype match were further studied by using multiplex ligation-dependent probe amplification (MLPA) or Sanger sequencing. All MMCA results were automatically analyzed and manually checked. The consistency between MMCA assay and conventional methods among prenatal samples was investigated. Except for initiation codon (T>G) (HBB:c.2T>G), all genotypes of thalassemia inside the scope of conventional methods were detected by MMCA assay. Additionally, 27 carriers with 10 rare HBB variants, 13 with α fusion gene, 1 with a rare deletion in α globin gene, and 1 with rare HBA variant were detected by using MMCA assay. MMCA can be an alternative approach used in routine thalassemia carrier screening and prenatal diagnosis for its high throughput, sufficient stability, low cost, and easy operation.

Adolescents' experiences and views of the national school-based thalassaemia screening programme in Malaysia: a qualitative study.

In 2016, a national school-based thalassemia screening programme was implemented in Malaysia. This study aimed to explore the experiences and views of adolescents from an urban school who had undergone the screening programme. We carried out in-depth interviews with 18 participants aged between 18 and 19 years old, with 12 of them identified as carriers during the school screening. Interviews were transcribed verbatim and analysed using thematic analysis. Three main themes emerged from this study: (1) issues encountered at various levels of the school screening programme: appropriate age for screening, thalassaemia education in school, parental consent and follow-up visit and post-test counselling; (2) experiencing emotional rollercoaster: worry, anxiety, shame, stigma; (3) choosing future partners after carrier status was known-prepared or unprepared? Various issues and screening-related challenges were encountered before, during and after the screening test. Recommendations include improving thalassaemia screening education for both school-going adolescents and parents, and better follow-up care and support for those identified as carriers. These will help stakeholders to be well informed and supportive of thalassaemia screening in schools.

Rare and New Mutations of B-Globin in Azari Population of Iran, a Considerable Diversity.

Thalassemia, as the most common single-gene genetic disorder, is related to a defect in the synthesis of one or more hemoglobin chains. More than 200 mutations have been identified in the β-globin gene. Globally, every susceptible racial group has its own specific spectrum of the common mutations that are well-known to a particular geographic region. On the other hand, varying numbers of diverse rare mutations may occur. The subjects of the study included 2113 heterozygote or homozygote β-thalassemia cases selected among couples who participated in the Iranian national thalassemia screening program from January 2011 to November 2019. Molecular characterization of the β-thalassemia mutation was initially carried out by the amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) technique for common mutations, followed by sequencing, Gap PCR, and Multiple ligation-dependent probe amplification (MLPA) methods - in cases not detected by the ARMS-PCR. The existence of 39 rare and new point mutations and 4 large deletions were described in our cohort. Sicilian (-13,337bp) deletion, CD36/37 (-T), and CD15 TGG>TGA were encountered more often than the others in a decreasing order, in terms of frequency. The least frequent mutations/deletions were deletion from HBD exon 1 to HBB promoter, 619 bp deletion, Deletion from up HBBP1-Exon3 HBBP1 and up HBB-0.5Kb down HBB, CAP+8 C>A, CD37 (G>A), CD6 (-A), IVSI-2 (T>C), IVSII-705 T>G, and IVSII-772 (G>A). Each occurred once. Five mutations/variants were also determined which have not been reported previously in Iran. According to the findings of the study, the Northwestern Iranian population displayed a wide variety of thalassemia allelic distributions. Identification of rare and new mutations in the β-thalassemia in the national population is beneficial for screening programs, genetic counseling, and prenatal diagnosis.

Significant haemoglobinopathies: A guideline for screening and diagnosis: A British Society for Haematology Guideline: A British Society for Haematology Guideline.

Antenatal screening/testing of pregnant women should be carried out according to the guidelines of the National Health Service (NHS) Sickle Cell and Thalassaemia Screening Programme. Newborn screening and, when necessary, follow-up testing and referral, should be carried out according to the guidelines of the NHS Sickle Cell and Thalassaemia Screening Programme. All babies under 1 year of age arriving in the United Kingdom should be offered screening for sickle cell disease (SCD). Preoperative screening for SCD should be carried out in patients from ethnic groups in which there is a significant prevalence of the condition. Emergency screening with a sickle solubility test must always be followed by definitive analysis. Laboratories performing antenatal screening should utilise methods that are capable of detecting significant variants and are capable of quantitating haemoglobins A2 and F at the cut-off points required by the national antenatal screening programme. The laboratory must ensure a provisional report is available for antenatal patients within three working days from sample receipt.

Molecular and haematological characterization of deletional alpha thalassemia in northeastern Malaysia

Background: Alpha (α) thalassemia is an inherited condition that often cause public health problem in Malaysia. Thalassemia screening program plays extremely important roles for early detection. Therefore, it is important to accurately characterized molecular and hematologic parameters to determine the carrier genotype and prevent thalassaemia major or intermedia offspring. Objective: The objective of this study is to detect α-globin gene deletions and evaluate the haematological parameters among deletional α thalassemia patients in Hospital Universiti Sains Malaysia, Northeastern Malaysia. Result: 71 (33.2%) out of of 214 samples in this study, were detected with α thalassaemia deletional type. South-East Asian (SEA) (50.7%) was most common type α deletional thalassaemia detected. There was a significant difference between the median of Hb, MCV and MCH level of patients with and without α deletion. Conclusion: This study highlighted the importance of hematological parameter as well as Hb analysis to be used as a guide before proceed with molecular method in establishing a definitive diagnosis for proper management. Bangladesh Journal of Medical Science Vol. 22 No. 02 April’23 Page : 410-415

Thalassemia prevention: Religious and cultural barriers to premarital screening in Bangladesh.

Thalassemia prevention: Religious and cultural barriers to premarital screening in Bangladesh.

A rare presentation of sickle cell disease diagnosed for the first time in a 60-year-old female: A misdiagnosis or missed diagnosis

Sickle cell disease (SCD) mainly manifests in early childhood. During the first 6 months of life, infants are largely protected by high levels of hemoglobin F; soon thereafter, the disease becomes evident in form of various crises such as vaso-occlusive crisis, hemolytic crisis, and acute chest syndrome, and in rare instances aplastic crisis. Therefore, the majority of patients with SCD are diagnosed in childhood or adulthood, whereas those with sickle cell trait usually remain asymptomatic. However, here, we are presenting a rare case in which a patient has been diagnosed to have SCD for the 1st time at the age of 60 years while being treated for dengue and severe anemia. Our case is one of the rare presentations of SCD, as she never required any blood transfusions even during childbirth and without any sickle crises; therefore, she might not be diagnosed with SCD till her presentation to our hospital. This indicates that advanced age should not be considered as an exclusion criterion for the suspecting and diagnosis of SCD. This case outlines the need for awareness and incorporation of screening for sickle cell anemia in childhood or adulthood as same thalassemia screening programs. The early diagnosis by screening programs will ensure appropriate treatment and therefore improve the quality of life in such patients.

Targeted Next-Generation Sequencing Reveals a Large Novel β-Thalassemia Deletion that Removes the Entire HBB Gene

β-Thalassemia (β-thal) is one of the most common monogenic recessive inherited diseases worldwide. The mutation spectrum of β-thal has been increasingly broadened by various genetic testing methods. The discovery and identification of novel and rare pathogenic thalassemia variants enable better disease prevention, especially in high prevalence regions. In this study, a Chinese thalassemia family with an unclear etiology was recruited to the Thalassemia Screening Program. Blood samples collected from them were primarily screened by hematology analysis and clinical routine genetic screening. Subsequently, targeted next-generation sequencing (NGS) and Sanger sequencing were performed to find and identify a novel deletion variant. The deletion, discovered by targeted NGS, was validated through real-time quantitative polymerase chain reaction (qPCR). First, a large novel β-thal deletion (3488 bp) related to a high Hb F level, NC_000011.9: g.5245533_5249020del (Chongqing deletion) (GRCh37/hg19), was found and identified in the proband and her mother. The deletion removed the entire β-globin gene and led to absent β-globin (β0). We then validated this large novel deletion in the proband and her mother by qPCR. We first discovered and identified a large novel β-thal deletion related to elevated Hb F level, it helps broaden the spectrum of pathogenic mutants that may cause β-thal intermedia (β-TI) or β-thal major (β-TM), paving the way for effective thalassemia screening. Next-generation sequencing has the potential of finding rare and novel thalassemia mutants.

Co-Inheritance of Heterozygous β0-Thalassemia with Single Functional α-Globin Gene: Challenges of Carrier Detection in Pre-Marital Screening Program for Thalassemia

This is a report of a couple with abnormal hematological indices who were investigated for α &amp; β-thalassemia mutations. Based on CBC and capillary hemoglobin electrophoresis results, the male and female subjects were β &amp; α-thalassemia carriers, respectively. Multiplex-Gap-PCR and Sanger sequencing techniques were used for the identification of mutations on α and β-globin genes. The DNA test showed the presence of c.315 + 1 G &gt; A mutation on β-globin gene of male subject while the female case had – MED double gene deletion and c.427T &gt; C mutation on α-globin and, interestingly, she was also a carrier for c.315 + 1 G &gt; A mutation on β-globin gene. Cases with the coinheritance of heterozygous β0-thalassemia with one functional α-globin gene have normal HbA2 levels that may lead to their being misdiagnosed as β-thalassemia carriers, especially in premarital screening programs for thalassemia. Therefore, β-globin gene sequencing is recommended in cases with normal Hb electrophoresis and reduced hematological indices in premarital screening programs for thalassemia, especially in regions with a high frequency of β-globin mutations, in order to identify all the β-thalassemia carriers.

Extended family thalassemia screening as a feasible alternative method to be implemented in identifying carriers in West Java, Indonesia

The thalassemia screening program in Indonesia mostly conducted sporadically. Ideal prospective screening is still limited. This study aimed to compare thalassemia screening methods using the extended family approach with and without a history of severe thalassemia and the feasibility of implementing extended family screening method. A case control study was conducted in Dr. Hasan Sadikin General Hospital Bandung with 3 generations of extended families. Data were collected from 150 subjects of 8 extended families with severe thalassemia as an index case entry and 151 subjects of 12 families with no history of thalassemia. All subjects were examined for Hb, MCV, MCH, and peripheral blood smear (PBS) as initial laboratory examinations. Subjects with MCV < 80 fL, MCH < 27 pg, and suggestive findings on PBS continued hemoglobin analysis. Carrier status was determined by definition. All subjects consented to undergo screening and voluntarily participated. The proportion of thalassemia carriers and the participation rate between the 2 groups were compared. Sixty-four of 150 (42.7%) and 16 of 151 (10.6%) carriers were identified in both the case and control group (p < 0.001). The participation rate was 42–88 vs. 23–100% (p = 0.244). The mean age was 31.9 ± 21.2 vs. 31.1 ± 20.8 years (p = 0.782). The median family size was 28.5 vs. 20 subjects per family (p = 0.245). The types of identified thalassemia carrier in both groups consisted of β-thalassemia, β-thalassemia/HbE, suspected α-thalassemia, and β-thalassemia Hb variant. All carriers continued the counseling process. The extended family method seems feasible to be implemented for thalassemia screening in West Java, Indonesia.

Molecular and Haematological Characteristics of alpha-Thalassemia Deletions in Yogyakarta Special Region, Indonesia.

alpha-Thalassemia is caused primarily by deletions of one to two alpha-globin genes and is characterized by absent or deficient production of alpha-globin protein. The South-East Asia (SEA) deletion, 3.7-kb and 4.2-kb deletions are the most common causes. The present study aimed to observe the molecular characteristics of this common alpha-Thalassemia deletions and analyse its haematological parameter. Blood samples from 173 healthy volunteers from thalassemia carrier screening in Yogyakarta Special Region were used. Haematological parameters were analysed and used to predict the carrier subjects. Genotype of suspected carriers was determined using multiplex gap-polymerase chain reaction and its haematological parameters were compared. The boundary site of each deletion was determined by analysing the DNA sequences. Seventeen (9.8%) of the volunteers were confirmed to have alpha-Thalassemia trait. Of these, four genotypes were identified namely -α3.7/αα (58.8%), -α4.2/αα (5.9%), -α3.7/-α4.2 (5.9%) and - -SEA/αα (29.4%). The 5' and 3' breakpoints of SEA deletion were located at nt165396 and nt184700 of chromosome 16, respectively. The breakpoint regions of 3.7-kb deletion were 176-bp long, whereas for 4.2-kb deletion were 321-bp long. The haematological comparison between normal and those with alpha-Thalassemia trait genotype indicated a significant difference in mean corpuscular volume (MCV) (p< 0.001) and mean corpuscular haemoglobin (MCH) (p< 0.001). As for identifying the number of defective genes, MCH parameter was more reliable (p= 0.003). The resultant molecular and haematological features provide insight and direction for future thalassemia screening program in the region.

Splice-site and Frameshift Mutations of β-Globin Gene Found in Thalassemia Carrier Screening in Yogyakarta Special Region, Indonesia

BACKGROUND: β-thalassemia is an inherited blood disorder that relatively common in Southeast Asian countries. In Indonesia, it is estimated that 200,000 infants with thalassemia carrier born each year. Mutation causing β-thalassemia is highly varied and relatively specific in a population. This study aimed to identify the mutations responsible for β-thalassemia from Thalassemia Carrier Screening conducted in Yogyakarta Special Region. This information is beneficial for developing a strategic prevention program to control thalassemia in the region.METHODS: Twenty-eight blood samples of haematologically suspected β-thalassemia from participant of thalassemia screening program in Yogyakarta Special Region were investigated for β-globin gene mutation by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), amplification refractory mutation system (ARMS) and DNA sequencing.RESULTS: Our samples showed average HbA2 value of 5±0.81% and HbF value of 2±2.29%. It showed eight abnormal erythrocyte morphologies dominated by hypochromia (96.4%), cigar cell (85.7%), and microcytosis (78.6%). Our molecular investigation identified three splice-site mutations namely InterVening Sequence (IVS)-1-5 (G&gt;C) (71.4%), IVS-1-2 (T&gt;C) (7.1%), and IVS-1-1 (G&gt;T) (3.6%), two frameshift mutations that are CD35 (-C) (10.7%) and CD8/9 (+G) (3.6%), and a missense mutation of CD6 (GAG&gt;GTG) (3.6%).CONCLUSION: Our study concluded on a high prevalence of IVS-1-5 (G&gt;C) mutation in Yogyakarta Special Region. This mutation information is significant for developing a strategic prevention program to control thalassemia in the region, for example for developing a rapid molecular test for future screening program.KEYWORDS: β-Globin gene, thalassemia, screening, carrier, mutation, Yogyakarta

In silico prediction of HBD gene variants in the Iranian population

BackgroundThe quantification of hemoglobin A2 (Hb A2; α2δ2) is used as a valuable test to differentiate α- and ß-thal carriers in clinical laboratories. Therefore, the HBD (δ-globin) gene variants could result in reduced levels of Hb A2 and have implications for thalassemia screening programs. The aim of the present study was to predict the consequences of HBD gene variants identified in the Iranome project.ResultsThe highest number of variants was in the Persian Gulf Islanders. The variants of p.Gln132Glu (HBD: c.394C>G), p.Gly17Arg (HBD: c.49G>C), p.Thr5Ile (HBD: c.14C>T), and p.Ala28Ser (HBD: c.82G>T) presented damage results in three or more prediction tools. In addition, it seems that the p.Gly30= (HBD: c.90C>T) decreases the use of authentic splice and, instead, creates a new donor splice site (DSS) or leads to the use of a cryptic DSS.ConclusionsMost of these variants have been associated with a decrease in Hb A2 levels. Due to the high mutational diversity in the HBB gene in the Iranian population and the use of Hb A2 quantification to differentiate α- and ß-thal carriers among Iranian clinical laboratories, some attention should be taken to a possible co-inheritance of HBD gene variants to avoid the misdiagnosis of ß-thal carriers.

Major Thalassemia, Screening or Treatment: An Economic Evaluation Study in Iran.

Beta-thalassemia minor and thalassemia major are an autosomal recessive disease with hypochromic, microcytic anemia, and morbidities, Today, therapeutic advances have significantly improved the life expectancy of thalassemia major patients, but at the cost of financial toxicity. The present study aimed to investigate the possibility of increasing the funding for thalassemia screening programs and comparing the cost-effectiveness of screening for thalassemia in the treatment of the patients. In this study, screening for thalassemia minor was compared with the treatment of thalassemia major patients. A decision tree model was used for analysis. A hospital database, supplemented with a review of published literature, was used to derive input parameters for the model. A lifetime study horizon was used and future costs and consequences were discounted at 3%. The approach of purchases of services was used to evaluate the screening test costs for patients with thalassemia major. Also, a bottom-up method was applied to estimate other screening and treatment costs. All the costs were calculated over one year. The number of gained quality-adjusted life years (QALYs) was calculated using the EQ-5D questionnaire in the evaluated patients. In this study, 26.97 births of patients with thalassemia major were prevented by screening techniques. On the other hand, total screening costs for patients with thalassemia major were estimated equal to US$ 879879, while the costs of preventing the birth of each thalassaemia major patient was US$ 32 624 by screening techniques. In comparison, the cost of managing a patient with thalassemia major is about US$ 136 532 per year. The life time QALYs for this is 11.8 QALYs. Results are presented using a societal perspective. Incremental cost per QALY gained with screening as compared with managing thalassaemia major was US$ 11 571. Screening is a long-term value for money intervention that is highly cost effective and its long-term clinical and economic benefits outweigh those of managing thalassaemia major patients.

Epidemiology of Thalassemia in Gulf Cooperation Council Countries: A Systematic Review.

Background Thalassemia has a burden on the healthcare systems of many countries. About 56000 conceptions result in thalassemia, globally. Objective To assess the epidemiological profile of thalassemia in the Gulf Cooperation Council (GCC) countries. Methods A systematic search was conducted in MEDLINE/PubMed (National Library of Medicine), CINAHL, and Embase. Relevant observational studies reporting the epidemiology of thalassemia among the GCC population were selected. Data on the prevalence, frequency, and complications of thalassemia were extracted. The quality of the retrieved studies was assessed according to the Newcastle–Ottawa Quality Assessment Scale. Results Eighteen studies (14 cross-sectional studies, two retrospective observational studies, and two retrospective analysis) with a total of 3343042 participants were included in this systematic review. Of the 18 studies, 11 studies were conducted in Saudi Arabia, two in the Kingdom of Bahrain, one in Kuwait, three in the United Arab Emirates (UAE), and one in Qatar. The prevalence of thalassemia among children below five years of age ranged from 0.25% to 33%, while it was 0.9% in children above five years and from 0.035% to 43.3% among adult thalassemia patients. The most-reported risk factors were consanguineous marriage and high-risk marriage. There was a lack of data regarding mortality rates in thalassemia. Conclusions Despite the premarital screening and genetic counseling (PMSGC) program for thalassemia, the incidence of high-risk couple marriages in GCC countries cannot be effectively diminished. This study suggested that the PMSGC program should adopt more attention for the high-risk areas, to enhance the level of consciousness about the hemoglobinopathy diseases and the consequences of consanguinity among the at-risk couple.

Prevalence of Alpha(α)-Thalassemia in Southeast Asia (2010-2020): A Meta-Analysis Involving 83,674 Subjects.

Alpha(α)-thalassemia is a blood disorder caused by many types of inheritable α-globin gene mutations which causes no-to-severe clinical symptoms, such as Hb Bart’s hydrops fetalis that leads to early foetal death. Therefore, the aim of this meta-analysis was to provide an update from year 2010 to 2020 on the prevalence of α-thalassemia in Southeast Asia. A systematic literature search was performed using PubMed and SCOPUS databases for related studies published from 2010 to 2020, based on specified inclusion and exclusion criteria. Heterogeneity of included studies was examined with the I2 index and Q-test. Funnel plots and Egger’s tests were performed in order to determine publication bias in this meta-analysis. Twenty-nine studies with 83,674 subjects were included and pooled prevalence rates in this meta-analysis were calculated using random effect models based on high observed heterogeneity (I2 > 99.5, p-value < 0.1). Overall, the prevalence of α-thalassemia is 22.6%. The highest α-thalassemia prevalence was observed in Vietnam (51.5%) followed by Cambodia (39.5%), Laos (26.8%), Thailand (20.1%), and Malaysia (17.3%). No publication bias was detected. Conclusions: This meta-analysis suggested that a high prevalence of α-thalassemia occurred in selected Southeast Asia countries. This meta-analysis data are useful for designing thalassemia screening programs and improve the disease management.