Contemporary etiologies of crossmatch-incompatible red blood cell transfusions in non-emergent settings

The crossmatch is a critical component of pretransfusion testing for red blood cell (RBC) units and represents the final assessment of compatibility between the donor unit and transfusion recipient. Contemporary studies describing the etiologies and clinical outcomes of incompatible RBC transfusions are limited. In this single-center, retrospective study, all crossmatch-incompatible RBC transfusions performed over a 2.5-year period (May 2022-December 2024) were reviewed. Only RBC units approved for issue by a transfusion medicine physician and subsequently transfused to patients were included. Data collected included the etiologies of crossmatch incompatibility, patient red cell immunization status, and any transfusion reactions associated with incompatible RBC transfusions. During the study period, 13,461 full serologic crossmatches were performed, and 52 unique patients received a total of 142 crossmatch-incompatible RBC transfusions. Incompatibility was most commonly attributable to autoantibodies, including 22 patients (42%) with both warm and cold autoantibodies, 14 (27%) with warm autoantibodies alone, and 3 (6%) with cold autoantibodies alone. Nine patients (17%) had crossmatch incompatibility due to monoclonal antibody therapy and four (8%) due to alloantibodies. No cases of acute or delayed hemolytic transfusion reactions were observed. The majority of patients (75%) received crossmatch-incompatible RBC transfusions in the setting of red cell autoantibodies. Monoclonal antibody therapy emerged as a contemporary cause of RBC crossmatch incompatibility in a subset of patients. Overall, incompatible RBC units approved by transfusion medicine physicians were not associated with acute or delayed hemolytic transfusion reactions.