Abstract
Background/Objectives: Blood transfusion is a crucial component in the treatment of individuals with sickle cell disease [SCD]; nonetheless, multiple transfusions can lead to considerable complications, notably alloimmunization. However, the prevalence of alloimmunization and its predictors remain incompletely explained. This review aimed to determine its global prevalence and identify associated risk factors. Method: Our protocol was registered in PROSPERO [ID: CRD420251167042] in accordance with the PRISMA 2020 criteria. A thorough literature search was conducted across PubMed, Embase, Web of Science, Scopus, and the Cochrane Library to identify studies reporting the prevalence of alloimmunization in adults with confirmed sickle cell disease who have received blood transfusions. This search included all publications up to 16 April 2026. Two reviewers independently screened and extracted data, and the Newcastle–Ottawa Scale was used to evaluate the study’s quality. After the Freeman–Tukey transformation, a random-effects model was used to estimate the pooled prevalence. We examined disparities among groups and geographies, study designs, and matching procedures to determine their differences. We additionally employed meta-regression to identify potential predictors. Results: Nine studies [n = 1711; 1978–2026] met the inclusion criteria. The overall rate of alloimmunization was 28.9% [95% CI 22.4–35.4; I2 = 88.5%]. The most prevalent antibodies were those of the Rh and Kell systems, with anti-E antibodies being the most frequent, followed by anti-C and anti-K antibodies. A higher number of transfusions and the HbSβ0 genotype were both persistent risk factors, while older age at first transfusion appeared protective. Extended antigen matching dramatically reduced prevalence, though approximately 9% of individuals remained affected. Conclusions: Alloimmunization continues to challenge transfusion management in adults with SCD. Broader implementation of extended antigen matching and genotype-informed transfusion strategies may help mitigate this risk.