THE EFFECTIVENESS OF EXTENDED ANTIGEN MATCHING IN REDUCING ALLOIMMUNIZATION AMONG CHRONICALLY TRANSFUSED PATIENTS: A SYSTEMATIC REVIEW

Abstract

Background: Red blood cell (RBC) alloimmunization remains a major clinical challenge among chronically transfused patients, particularly those with sickle cell disease (SCD), β-thalassemia, and myelodysplastic syndromes (MDS). Despite standard ABO and RhD compatibility, antigenic disparities between donors and recipients lead to alloantibody formation and increase the risk of delayed hemolytic transfusion reactions (DHTRs). This systematic review aimed to evaluate the effectiveness of extended RBC antigen matching—including Rh, Kell, Duffy, Kidd, and MNS systems—in reducing alloimmunization and improving transfusion safety. Methods: Following the PRISMA 2020 guidelines, peer-reviewed studies published between 2013 and 2025 were systematically reviewed from databases including PubMed, Scopus, Web of Science, and Embase. Eligible studies focused on chronically transfused patients who received prophylactic or extended RBC antigen matching compared with standard matching. Data were synthesized narratively due to heterogeneity in population characteristics and transfusion protocols. Results: Ten studies met the inclusion criteria. Across SCD, β-thalassemia, and MDS populations, extended antigen matching significantly reduced alloimmunization rates, with reported declines from 47% to 23.5% (Leal et al., 2023) and from 23% to 11% (Lin et al., 2017). Molecular genotyping further minimized Rh variant-related mismatches, while implementation of comprehensive Rh and Kell matching protocols led to marked reductions in both alloimmunization and transfusion-related complications (Belsito et al., 2019; Waldis et al., 2021). The approach was also found to be cost-effective in long-term management (Kacker et al., 2014). Conclusion: Extended and molecular RBC antigen matching demonstrates a clear benefit in reducing alloimmunization and transfusion complications across chronically transfused populations. Integrating molecular typing, genotyped donor registries, and risk-based matching policies into transfusion programs may represent the next standard of care for improving patient safety and transfusion outcomes globally.