Red cell antibody and antigen patterns in patients with sickle cell disease: A multi‐center analysis

BACKGROUND: Red cell alloimmunization complicates sickle cell disease (SCD) management despite current widespread prophylactic Rh/K matching in the United States (US). Regional antibody patterns remain poorly characterized. STUDY DESIGN AND METHODS: We conducted a retrospective analysis of 2965 SCD patients from 9 US sites (2010-2022). All hospitals prophylactically match for Rh and K antigens. Each site collected demographics, antigen status, antibody histories, and antibody screen results from their laboratory information system. RESULTS: Overall antibody prevalence was 29.7% with dramatic institutional variation (17.9%-56.0%). Alloantibody prevalence was 27.5%. Most autoantibody-positive patients (74.23%) also had alloantibodies, identifying a high-risk population. A third of patients with positive antibody histories had negative screens. Pediatric patients showed markedly different antibody profiles than adults. Hospitals' antibody patterns clustered by patient age rather than geography. Rh and K antibodies were the most common and also most likely to co-occur, followed by S, Fya, and Jkb antibodies. Antibodies against Jsa (1.82%), V (1.75%), and Kpa (1.69%) were more prevalent than anti-Jka (1.28%). Despite regional antibody variation, antigen frequencies remained overall consistent. In antigen-antibody pairwise comparisons, 3.15% were antigen-negative and antibody-positive reflecting alloimmunization; 0.47% were both antibody- and antigen-positive, suggesting partial/variant antigens. DISCUSSION: Substantial institutional variation in antibody prevalence suggests need for site-specific approaches to testing and prophylactic matching. High co-occurrence of auto- and alloantibodies, antibody immunogenicity patterns, and antigen-antibody discordances support the need for further research and consideration of refined testing and/or matching strategies beyond the current Rh and K standard.