Hemato, Volume 6, Issue 4 (December 2025) – 2 articles

Background: Haemoglobinopathies are among the most common monogenic disorders worldwide. Early identification of asymptomatic carriers through reliable screening and molecular diagnostics is crucial for prevention programmes, especially in high-prevalence regions such as Southern Italy. Methods: A total of 5243 individuals were analysed between 2013 and 2024 using both biochemical and genetic parameters. First-level screening included full blood count, iron status, and high-performance liquid chromatography (HPLC) for haemoglobin variant quantification. Molecular analyses were performed using next-generation sequencing (NGS) for the HBA1, HBA2, and HBB genes. Results: We identified 267 individuals (11.2%) as carriers of α-thalassaemia and 473 individuals (16.7%) as carriers of β-thalassaemia. Among them, 5 were compound heterozygotes and 3 homozygous for the α-3.7 deletion. A rare case of HbG Philadelphia in association with a triplicated α-gene was also observed. The most common β-globin mutations included c.118C>T (β⁰39, 44%), IVS-I-110 (17.7%), IVS-I-6 (12.7%), and IVS-I-1 (12.3%). Among α-globin mutations, the most prevalent were -α^3.7 (48%), α2 IVS1 -5nt (15.4%), -20.5 Kb (14.2%), and triplicated α (11%). In total, 18.7% of individuals were found to carry either α- or β-thalassaemia traits. Conclusion: Our findings highlight the limitations of traditional diagnostic methods—such as the osmotic fragility test—and the importance of integrating haematological, biochemical, and molecular data to accurately identify thalassaemia carriers. The variability of genotype–phenotype correlations, especially in the context of immigration and genetic diversity, underscores the need for comprehensive molecular analysis. We propose a three-step diagnostic algorithm combining first-level screening, iron status assessment, and NGS-based sequencing for inconclusive cases. Full article

Background/Objectives: Erythrocyte alloimmunization is a critical complication impacting the efficacy of transfusion therapy in patients with thalassemia. This study seeks to evaluate the prevalence, characterization, and determinants of erythrocyte alloimmunization in multi-transfused thalassemia patients in south of Morocco. Methods: A retrospective study was conducted at the Moroccan Blood and Blood Derivatives Agency in Marrakech (Morocco) over 2 years, from June 2022 to June 2024, including 89 patients with beta-thalassemia receiving regular transfusions. The clinical, demographic, and transfusion characteristics of patients who developed alloimmunization were compared with those of non-alloimmunized patients. Results: Analysis of 89 β-thalassemia patients in the Marrakech region, mostly young and suffering from major form (67%), shows a significant male predominance (p = 0.004) and a high frequency of blood group O+ (49.4%). Alloimmunization mainly affects major forms and males and is associated with frequent annual transfusions (over 12 per year), usually resulting in the use of 24 to 60 packed red blood cell units annually. Alloimmunized patients mostly present anti-K and anti-E antibodies, indicating the involvement of the Kell and Rh systems. The direct Coombs test was more often positive in these patients (21.4% vs. 7.9%, p < 0.01). Conclusions: The high prevalence of alloimmunization in thalassemia patients in the Marrakech region highlights the need for a rigorous and personalized transfusion strategy, including molecular genotyping and alternative therapies. Full article