Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, United States
Background/Case Studies: Infrequent antigens (IA) are rarely encountered in the donor population (< 10% donor frequency), but the risk of alloimmunization can occur in individuals who require frequent red cell transfusions. Routine antibody screening can miss these antibodies, and many are found via incompatible crossmatches. Moreover, alloantibodies to IA can become senescent, and whether antigen-matching strategies should include IA is a matter of debate. The current study aimed to identify the prevalence of senescent IA alloantibodies and the characteristics of the respective recipients.
Study
Design/Methods: We evaluated all reports of senescent antibodies to IA antigens from January 1, 2024 – May 1, 2025. At our institution, we provide PEG crossmatch-compatible units without antigen-negative confirmation of senescent IA after medical director approval. The electronic medical record was used to define recipient age, race, ethnicity, and underlying diagnosis. We further defined whether the senescent antibody subsequently became detectable post-transfusion or if a direct Coombs test became positive.
Results/Findings: During the study period, 36 unique individuals had 191 reported transfusion events involving 748 crossmatch-compatible units involving a senescent IA. Half of the recipients were female and a majority identified as Black (n=21, 58%). Nineteen recipients (53%) had sickle cell disease (SCD) and 16 (84%) of the SCD patients were receiving chronic exchanges. The majority (8/17, 47%) of non-SCD patients had a hematologic malignancy. Exchange recipients with SCD represented 86% (643/748) of all transfused units. The three most common senescent antibodies in Black recipients were Jsa (n=6, 27%), Lua (n=4,18%), and V or Cw (n=3, 14%). The three most common in White/Hispanic recipients were Wra (n=4, 27%) and Lua or Cw (n=3, 20%). Senescent anti-Wra represented the antibody with the largest overall transfusion burden (198/748, 27%) (Table 1). Reactivation of IA antibodies was identified in 13 (68%) recipients with SCD and 7 (41%) recipients without SCD, but no positive direct Coombs test was noted. Only recipients with SCD (2/19, 11%) had crossmatch incompatible units identified when IA antibodies were knowingly present.
Conclusions: We identified that senescent alloantibodies to IA in our cohort disproportionately impacted Black individuals with SCD. Many of them were on chronic transfusion protocols, increasing their overall risk of encountering these antigens. We identified a greater number of IA reactivations and more incompatible crossmatches in those with SCD, and so caution should be used, especially for chronically transfused patients with SCD who are at increased risk of delayed hemolytic reactions or hyperhemolysis.
