Advances in Hemoglobinopathies and Thalassemia Evaluation.

Hemoglobin (Hb) disorders are among the most prevalent inherited diseases. Despite a limited number of involved genes, these conditions represent a broad clinical and prognostic spectrum. The menu of laboratory tests is extensive. From widely available modalities, for example, complete blood count to rather sophisticated molecular technologies, the investigation of Hb disorders recapitulates an increasing complexity of laboratory workup in other medical fields. This review highlights a current state of biochemical and molecular investigation of Hb disorders and offers a glimpse on technologies that are yet to be fully embraced in clinical practice.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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 ß-thalassemia genotypes were mainly ß CD17/ßN (7.49%), ßCD41-42/ßN (6.70%), ßCD71-72/ßN (0.44%). 108 cases of moderate and severe ß-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. CONCLUSION: 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 ß-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.

Genome-wide methylation and gene-expression analyses in thalassemia.

Thalassemia is the most common autosomal genetic disorder in humans. The pathogenesis of thalassemia is principally due to the deletion or mutation of globin genes that then leads to disorders in globin-chain synthesis, and its predominant clinical manifestations include chronic forms of hemolytic anemia. However, research on the epigenetics and underlying pathogenesis of thalassemia is in its nascency and not yet been systematically realized. In this study, we compared the results of RNA-seq and the whole-genome bisulfite sequencing (WGBS) on 22 peripheral blood samples from 14 thalassemic patients and eight healthy individuals revealed a genome-wide methylation landscape of differentially methylated regions (DMRs). And functional-enrichment analysis revealed the enriched biological pathways with respect to the differentially expressed genes (DEGs) and differentially methylated genes (DMGs) to include hematopoietic lineage, glucose metabolism, and ribosome. To further analyze the interaction between the transcriptome and methylome, we implemented a comprehensive analysis of overlaps between DEGs and DMGs, and observed that biological processes significantly enriched the immune-related genes (i.e., our hypermethylated and down-regulated gene group). Hypermethylated and hypomethylated regions of thalassemia-related genes exhibited different distribution patterns. We thus, further identified and validated thalassemia-associated DMGs and DEGs by multi-omics integrative analyses of DNA methylation and transcriptomics data, and provided a comprehensive genomic map of thalassemia that will facilitate the exploration of the epigenetics mechanisms and pathogenesis underlying thalassemia.

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.

Nancy Olivieri: Sometimes, truth has only one face.

Nancy Olivieri is a senior haematologist and professor at the University of Toronto, Canada. In the early 1990s, she was conducting investigator-initiated research of an experimental drug, deferiprone, in children with thalassaemia, for which a pharmaceutical company, Apotex, started giving some supplemental support. In the course of her work, Dr Olivieri found that deferiprone might not be very effective and was also possibly toxic. When she signalled her intent to disclose the risks to participants, the trials were immediately shut down and she was threatened with "all legal remedies" should she disclose her concerns. This led to 18 years of attacks from the CEO of Apotex as well as fabricated charges and harassment from the University and the Hospital for Sick Children where she worked.

CRISPR/Cas12a-triggered ordered concatemeric DNA probes signal-on/off multifunctional analytical sensing system for ultrasensitive detection of thalassemia.

Based on CRISPR/Cas12a triggered ordered concatemeric DNA probes, a "on/off" self-powered biosensor is developed to achieve highly sensitive detection of thalassemia gene CD142 through open-circuit potential-assisted visual signal output. The ingeniously constructed glucose oxidase (GOD)-functionalized ordered concatemeric DNA probe structure can significantly amplify signal output, while the coupled CRISPR/Cas12a system is served as a "signal switch" with excellent signal-transducing capabilities. When the ordered concatemeric DNA probe structure is anchored on electrode, the response signal of the sensing system is in the "signal on" mode. While, the presence of the target activates the non-specific cleavage activity of the CRISPR/Cas12a system, causing the sensing system to switch to the "signal off" mode. In the detection system, GOD catalyzes the oxidation of glucose to produce hydrogen peroxide, which further catalyzes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to form a color product, enabling visual signal of the target through naked-eye color contrast. By employing a multifunctional analytical mode combining electrochemical and visual signal outputs, accurate determination of the target is achieved, with linear ranges of 0.0001-100 pM, and detection limits of 48.1 aM (S/N = 3). This work provides a reference method for sensitive detection of thalassemia genes and holds great diagnostic potential in biomedical applications.

Adipocyte fatty acid-binding protein (FABP4) as a potential biomarker for predicting metabolically driven low-grade and organ damage in thalassemia syndromes.

Adipocyte fatty acid-binding protein (A-FABP; FABP4) plays a significant role in the pathogenesis and progression of metabolically driven low-grade inflammation and organ damage. This study aimed to evaluate the performance of circulating FABP4 as a predictive and diagnostic biomarker for thalassemia-associated cardiometabolic events. This case-control study enrolled 50 adults with ß-thalassemia and 30 age-, sex-, and body mass index-matched controls. Participants underwent a comprehensive evaluation, including complete blood count, liver and kidney function tests, serum blood glucose, lipid profile, and ferritin levels, pelviabdominal ultrasound, ECG, and echocardiography after taking a full medical history and conducting a clinical examination. Serum levels of FABP4 were measured using an Enzyme-Linked-Immunosorbent-Assay. The diagnostic performance of FABP4 was assessed using receiver operator characteristic (ROC) curve analysis to determine optimal values for excluding and confirming cardiometabolic metflammation. The thalassemia cohort exhibited a statistically significant higher concentration of FABP4 compared to the control group (p-value < 0.001). Positive correlations were found between FABP4 and ferritin serum levels above 800 or 1000 ug/L, as well as with ALT, TGS, and LDL (p-value < 0.05). Circulating FABP4 was identified as a statistically significant risk factor for thalassemia-associated cardiometabolic comorbidities (OR = 84.00, 95%CI:18.6-378.6, p-value < 0.001). ROC analysis determined that the FABP4 exclusionary cut-off value > 2.30 ng/ml could effectively discriminate between thalassemia-associated adverse metaflammation and controls, while the FABP4 confirmatory cut-off value was > 2.58 ng/ml. In conclusion, circulating FABP4 appears to be a potential risk factor for predicting progression to cardiometabolic events in thalassemia-associated adverse metaflammation. FABP4 holds promise as a diagnostic and prognostic biomarker for disease monitoring and risk stratification. Further validation through large-scale, multicenter, prospective studies is warranted.

Global, regional, and national burden of thalassemia during 1990-2019: A systematic analysis of the Global Burden of Disease Study 2019.

INTRODUCTION: Thalassemia represents a significant public health challenge globally. However, the global burden of thalassemia and the disparities associated with it remain poorly understood. Our study aims to uncover the long-term spatial and temporal trends in thalassemia at global, regional, and national levels, analyze the impacts of age, time periods, and birth cohorts, and pinpoint the global disparities in thalassemia burden. METHODS: We extracted data on the thalassemia burden from the Global Burden of Disease Study (GBD) 2019. We employed a joinpoint regression model to assess temporal trends in thalassemia burden and an age-period-cohort model to evaluate the effects of age, period, and cohort on thalassemia mortality. RESULTS: From 1990 to 2019, the number of thalassemia incident cases, prevalent cases, mortality cases, and disability-adjusted life years (DALYs) decreased by 20.9%, 3.1%, 38.6%, and 43.1%, respectively. Age-standardized rates of incidence, prevalence, mortality, and DALY declined across regions with high, high-middle, middle, and low-middle sociodemographic index (SDI), yet remained the highest in regions with low SDI and low-middle SDI as well as in Southeast Asia, peaking among children under five years of age. The global prevalence rate was higher in males than in females. The global mortality rate showed a consistent decrease with increasing age. CONCLUSION: The global burden of thalassemia has significantly declined, yet notable disparities exist in terms of gender, age groups, periods, birth cohorts, SDI regions, and GBD regions. Systemic interventions that include early screening, genetic counseling, premarital health examinations, and prenatal diagnosis should be prioritized in regions with low, and low-middle SDI, particularly in Southeast Asia. Future population-based studies should focus specifically on thalassemia subtypes and transfusion requirements, and national registries should enhance data capture through newborn screening.

Prevalence and risk factors predisposing low bone mineral density in patients with thalassemia.

Background: A common complication of thalassemia is secondary osteoporosis. This study aimed to assess the prevalence and factors associated with low BMD in thalassemic patients. Method: This is a cross-sectional study. Eligible patients were males aged within 18-49 years or premenopausal women diagnosed with thalassemia in Chiang Mai University Hospital between July 2021 and July 2022. The diagnosis of low BMD by dual-energy x-ray absorptiometry (DXA) was defined as a Z-score of -2.0 SD or lower in either the lumbar spine or femoral neck. Clinical factors associated with low BMD were analyzed using a logistic regression model. Results: Prevalence of low BMD was 62.4% from 210 patients with a mean age of 29.7 ± 7.6 years. The predominant clinical characteristics of low BMD thalassemia patients were being female, transfusion-dependent (TDT) and a history of splenectomy. From multivariable analysis, the independent variables associated with low BMD were transfusion dependency (odds ratio, OR 2.36; 95%CI 1.28 to 4.38; p=0.006) and body mass index (BMI) (OR 0.71; 95%CI 0.61 to 0.82; p<0.001). Among patients with low BMD, we observed a correlation between a Z-score with low IGF-1 levels (ß=-0.42; 95% CI -0.83 to -0.01; p=0.040), serum phosphate levels (ß=0.40; 95% CI 0.07 to 0.73; p=0.016) and hypogonadism (ß=-0.48, 95% CI -0.91 to -0.04, p=0.031). Conclusion: This study found a prevalence of low BMD in 62.4% of subjects. Factors associated with low BMD were TDT and BMI. Within the low BMD subgroup, hypogonadism, serum phosphate and low serum IGF-1 levels were associated with a lower Z-score.

Microstrip isoelectric focusing with deep learning for simultaneous screening of diabetes, anemia, and thalassemia.

BACKGROUND: Hemoglobin (Hb) is an important protein in red blood cells and a crucial diagnostic indicator of diseases, e.g., diabetes, thalassemia, and anemia. However, there is a rare report on methods for the simultaneous screening of diabetes, anemia, and thalassemia. Isoelectric focusing (IEF) is a common separative tool for the separation and analysis of Hb. However, the current analysis of IEF images is time-consuming and cannot be used for simultaneous screening. Therefore, an artificial intelligence (AI) of IEF image recognition is desirable for accurate, sensitive, and low-cost screening. RESULTS: Herein, we proposed a novel comprehensive method based on microstrip isoelectric focusing (mIEF) for detecting the relative content of Hb species. There was a good coincidence between the quantitation of Hb via a conventional automated hematology analyzer and the one via mIEF with R2 = 0.9898. Nevertheless, our results showed that the accuracy of disease diagnosis based on the quantification of Hb species alone is as low as 69.33 %, especially for the simultaneous screening of multiple diseases of diabetes, anemia, alpha-thalassemia, and beta-thalassemia. Therefore, we introduced a ResNet1D-based diagnosis model for the improvement of screening accuracy of multiple diseases. The results showed that the proposed model could achieve a high accuracy of more than 90 % and a good sensitivity of more than 96 % for each disease, indicating the overwhelming advantage of the mIEF method combined with deep learning in contrast to the pure mIEF method. SIGNIFICANCE: Overall, the presented method of mIEF with deep learning enabled, for the first time, the absolute quantitative detection of Hb, relative quantitation of Hb species, and simultaneous screening of diabetes, anemia, alpha-thalassemia, and beta-thalassemia. The AI-based diagnosis assistant system combined with mIEF, we believe, will help doctors and specialists perform fast and precise disease screening in the future.

Awareness and practical evaluation of correct use of iron chelators; a study to track the ambiguities of thalassemia patients on their medications in Iran.

PURPOSE: This study aimed to evaluate the knowledge, attitude, and practice toward iron chelating agents (ICAs) in Iranian thalassemia major patients. METHODS: A total of 101 patients with thalassemia major were involved in this cross-sectional survey. A deep medication review was done, and participants' knowledge, attitude, and practice were evaluated by a validated instrument based on a 20-scoring system. RESULTS: Statistical analyses showed 52 patients (51.5%) had a poor knowledge level (scores < 10) about their medications, 37 (36.6%) had a moderate level (scores 10-15), and 12 (11.9%) had a satisfactory level (scores > 15). Seventy-seven (76.2%) patients have positive beliefs regarding the dependence of their current health status on taking iron chelators, and 63 (62.4%) believed that they would become very ill without taking medication. The results also showed that the mean practice score in patients who received deferoxamine was 5.81 ± 3.50; in the patients who received deferiprone and those who received deferasirox, the mean scores were 7.36 ± 5.15 and 14.94 ± 4.14. Also, the knowledge and practice level had a direct linear correlation based on the regression analyses (P < 0.001). CONCLUSION: In conclusion, results of the present research suggests that the patients' knowledge about the administration, adverse events, and necessity of ICAs was not satisfactory. Improving the knowledge of thalassemia patients toward their medicines through educational interventions is highly recommended to improve their practice level.

Alterations in trace elements and cation profiles in transfusion-dependent thalassemia patients.

BACKGROUND: Transfusion-dependent thalassemia (TDT) is a severe form of beta-thalassemia, characterized by defective-globin production, resulting in a buildup of unpaired alpha globin chains. Patients with TDT can only survive if they receive safe blood transfusions regularly, which causes iron overload in their blood, which causes a variety of disorders. Cations and trace elements in TDT patients as a drug target deserve more studies. OBJECTIVES: In the present study, the cations and some trace elements were studied in TDT patients as a tool to adjust their level in the case of any disturbances. METHODS: Serum calcium, magnesium, zinc, copper, and iron were measured spectrophotometrically while manganese and cobalt were measured by flameless atomic absorption spectroscopy in 100 TDT patients and compared with 35 healthy control children. RESULTS: Patients with TDT exhibit a notable elevation in blood levels of iron, copper, copper/zinc ratio, and manganese, with a substantial reduction in serum levels of zinc, magnesium, calcium, and cobalt, as compared to the control group. These minerals have diverse associations with clinical data and transfusion frequencies. The receiver operating characteristic (ROC) analysis revealed that the elevated levels of iron, manganese, and calcium exhibit the greatest diagnostic capability, with a sensitivity and specificity of over 80 %, and a Youdin's J value of more than 0.6. CONCLUSION: The levels of cations and trace elements are disturbed in TDT patients. Hence, the monitoring and adjustment of the level of these minerals are important to prevent further consequences.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Bone mineral density in adult thalassaemias: a retrospective longitudinal study.

OBJECTIVES: In this study, we aim to evaluate the long-term impact of thalassaemia on bone mineral density (BMD) through sequential analysis, compare changes in BMD values between male and female patients and find any correlation between BMD and biochemical markers in the adult thalassaemia group. BMD is a bone mineral density test using dual-energy X-ray to measure calcium hydroxyapatite per unit of bone, reflecting bone strength. METHODS: We conducted a longitudinal retrospective observational cohort study to determine the changes in BMD values and biochemical parameters in adult thalassaemia patients. BMD was assessed at the lumbar spine (L1-L4) and proximal femora using Hologic's bone dual-energy X-ray absorptiometry. Five serial BMD values were retrieved from electronic records. Biochemical parameters, including serum calcium, phosphorus and 25-hydroxyvitamin D levels, were also assessed. RESULTS: A total of 108 patients (47 males and 61 females; median age: 44 years) with thalassaemia major 71 patients, intermedia 20 patients, haemoglobin E disease 14 patients and thalassaemia-alpha three patients were included. The incidence of low BMD in patients with thalassaemia increased from 64 to 74% over three decades of analysis. Females and thalassaemia major patients had lower hip BMD values and corresponding Z -scores. CONCLUSION: There is a progressive decline in BMD values in adult thalassaemia, which was apparent in female thalassaemia major patients. No changes in biochemical parameters, however, were observed over long-term assessments.

Universal Targeted Haplotyping by Droplet Digital PCR Sequencing and Its Applications in Noninvasive Prenatal Testing and Pharmacogenetics Analysis.

BACKGROUND: The analysis of haplotypes of variants is important for pharmacogenomics analysis and noninvasive prenatal testing for monogenic diseases. However, there is a lack of robust methods for targeted haplotyping. METHODS: We developed digital PCR haplotype sequencing (dHapSeq) for targeted haplotyping of variants, which is a method that compartmentalizes long DNA molecules into droplets. Within one droplet, 2 target regions are PCR amplified from one template molecule, and their amplicons are fused together. The fused products are then sequenced to determine the phase relationship of the single nucleotide polymorphism (SNP) alleles. The entire haplotype of 10s of SNPs can be deduced after the phase relationship of individual SNPs are determined in a pairwise manner. We applied dHapSeq to noninvasive prenatal testing in 4 families at risk for thalassemia and utilized it to detect NUDT15 diplotypes for predicting drug tolerance in pediatric acute lymphoblastic leukemia (72 cases and 506 controls). RESULTS: For SNPs within 40 kb, phase relation can be determined with 100% accuracy. In 7 trio families, the haplotyping results for 97 SNPs spanning 185 kb determined by dHapSeq were concordant with the results deduced from the genotypes of both parents and the fetus. In 4 thalassemia families, a 19.3-kb Southeast Asian deletion was successfully phased with 97 downstream SNPs, enabling noninvasive determination of fetal inheritance using relative haplotype dosage analysis. In the NUDT15 analysis, the variant status and phase of the variants were successfully determined in all cases and controls. CONCLUSIONS: The dHapSeq represents a robust and scalable haplotyping approach with numerous clinical and research applications.

The Decline of Open, Laparoscopic, and Robotic Splenectomies: A Single Center Experience.

Background: Splenectomy has been performed for various indications from haematological diseases to benign cysts and tumours, and for splenic traumatic injuries. However, there has been a steady decline in splenectomies in the last 20 years. The aim of this study is to establish the reasons behind this decline in splenectomy and to analyse them based on indication, type of splenectomy, and manner of approach (open, laparoscopic or robotic). Material and Methods: This is a retrospective study of a single centre experience of all the splenectomies, both total and partial, performed in the Department of General Surgery of Fundeni Clinical Institute (Bucharest) between 2002 and 2023. Only surgeries for primary splenic diseases were selected, splenic resections as part of other major operations were not included. Results: Between 2002 and 2023, 876 splenectomies were performed in the Department of General Surgery of Fundeni Clinical Institute (Bucharest). Most splenectomies (n=245) were performed for immune thrombocytopenic purpura (ITP), followed by benign tumours and cysts (n=136), lymphoma (n=119), hypersplenism due to cirrhosis (n=107) and microspherocytosis (n=95). Other indications included myelodysplastic syndrome (n=39), trauma (n=35), thalassemia (n=22), leukaemia (n=18) and also there were 60 splenectomies that were performed for hypersplenism of unknown cause. There were 795 total splenectomies (TS) and 81 partial splenectomies (PS). There was a decline in the number of splenectomies both TS and PS for all these indications, most notably in the case of ITP, microspherocytosis and hypersplenism due to cirrhosis with no splenectomies performed for these indications since 2020. Conclusion: With the development of new lines of treatment, advances in interventional radiology and in surgery with the spleen parenchyma sparing options, the need for total splenectomy has been greatly reduced which is reflected in the decline in the number of splenectomies performed in the last 20 years in our clinic.

A systematic review on thalassaemia screening and birth reduction initiatives: cost to success.

INTRODUCTION: Thalassaemia has been prevalent with high morbidity and mortality rates since 1925. Although there is a lack of systematic review on the costs of prevention that has yielded reductions in thalassaemia prevalence, this review will show a widespread presence of complex but effective strategies in reducing national thalassaemia prevalence. MATERIALS AND METHODS: A systematic search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020). Designated keywords were combined with search functions and Boolean operators in databases like Scopus, Web of Science and several other search databases. RESULTS: The search identifed 5425 potential articles. Most countries reported a decline in thalassaemia prevalence after implementing intervention programmes for several decades. The screening methods, however, varies, and the speed of reductions depends on the type of screening approach that involves blood screening of adolescence and antenatal mothers and, in some countries, includes termination of pregnancy. In addition, the cost of these initiatives varies as it was challenging to find a common denominator. However, the endpoint concedes that the cost of screening, although substantial, would be offset by the cost of reduction of cases. In some countries, cost-effectiveness analyses have been reported to support the initiatives of thalassaemia screening and prevention in the long run. CONCLUSION: The results showed significant variations in success rates with a significant reduction in the prevalence of Thalassaemia. Most successful are countries with comprehensive and aggressive prevention and control programmes that engaged with lab screening, counselling, and termination of pregnancy as a package.