Frequency of Alloimmunization in Patients on Regular Blood Transfusion in Riyadh, Saudi Arabia: A Multicenter Retrospective Study

<b>Background/Objectives</b>: Thalassemia and sickle cell anemia (SCA) patients require regular blood transfusions, a necessity that increases the risk of alloimmunization and complicates subsequent transfusion management. <b>Methods</b>: This retrospective cohort study, conducted at King Saud Medical City (KSMC) and King Fahad Medical City (KFMC) between 2018 and 2022, evaluated the frequency and risk factors of alloimmunization among 144 transfusion-dependent patients in Riyadh, Saudi Arabia. <b>Results</b>: By reviewing clinical and transfusion records alongside antibody screening results, the study found an overall alloimmunization prevalence of 20.1%. Notably, females exhibited a significantly higher rate (13.2%) compared to males (6.8%; <i>p</i> = 0.003), and younger patients (<20 years) showed a higher prevalence than older cohorts (<i>p</i> = 0.004). Analysis of ABO blood groups revealed that group A patients had a significantly lower alloimmunization rate (7.5%) compared to non-A patients (23.1%; <i>p</i> = 0.018), a finding that raises hypotheses about differential immune responsiveness but requires confirmation in larger studies. Group B showed the highest rate (35.3%), though this did not reach statistical significance after correction for multiple comparisons. RhD status was not significantly associated with alloimmunization. The most frequent alloantibodies identified were anti-E (31.3%), anti-K (12.5%), anti-D (10.4%), and anti-C (10.4%). Logistic regression further identified gender as a significant predictor (OR = 0.270; 95% CI: 0.113-0.646). <b>Conclusions</b>: Given that alloimmunization rates in Riyadh are moderately high-particularly among females and specific blood groups-and that the antibody profile (anti-E, anti-K, anti-C, anti-D) mirrors patterns seen in populations with recipient-donor ethnic mismatches, implementing extended blood group phenotyping for at least Rh (C, c, E, e) and Kell antigens prior to the first transfusion, and incorporating these findings into donor selection protocols, is critical to mitigating these risks.