#OA4-AM25-SN-09 - Contemporary Etiologies of Crossmatch Incompatible Red Blood Cell Transfusions

The crossmatch, a critical component of pretransfusion testing for red blood cell (RBC) units, serves as the final check of compatibility between a blood donor and transfusion recipient. Crossmatch incompatible RBCs may pose greater risk to patients for transfusion reactions, such as acute and delayed hemolysis. There is a lack of modern studies describing current etiologies and clinical outcomes associated with incompatible RBC transfusions. The purpose of this single-center, retrospective study was to describe contemporary causes and potential safety concerns associated with incompatible RBC transfusions.

Study

Design/Methods:

All crossmatch incompatible RBC transfusions were reviewed over a 2.5-year period (May 2022-December 2024). Only RBC units approved as safe for issue by the transfusion medicine physician and transfused to patients were included in the study. Etiologies of crossmatch incompatibility, patient red cell immunization status, and transfusion reactions, if any, associated with the incompatible RBC transfusions were collected.

Results/Findings:

During the study period in which 13,461 full crossmatches were performed, 53 unique patients received a total of 143 crossmatch incompatible RBC transfusions (Figure). Many patients had incompatibility due to autoantibodies, including 23 (43%) with both warm and cold alloantibodies, 14 (26%) with warm autoantibodies alone, and 3 (6%) with cold autoantibodies alone. Two of the warm autoantibodies showed anti-e specificity. Four patients (8%) demonstrated incompatibility due to an alloantibody (2 with anti-Knops, 1 with anti-Yta, and 1 with anti-P1); one of the patients with anti-Knops also had a cold autoantibody detected. Nine patients (17%) were on monoclonal antibody therapy (8 on daratumumab, 1 on magrolimab). Approximately half of all patients receiving incompatible RBCs (25/53, 47%) demonstrated a red cell alloantibody on pretransfusion testing. One patient experienced 2 transfusion reactions diagnosed as febrile non-hemolytic and transfusion-associated circulatory overload, both unrelated to incompatibility. No cases of acute or delayed hemolytic transfusion reactions occurred.

Conclusions:

The majority (75%) of patients received crossmatch incompatible RBC transfusions in the setting of red cell autoantibodies. Monoclonal antibody therapy interference emerged as a contemporary cause of RBC crossmatch incompatibility in a significant subset of patients, approximately 1-in-5. In general, incompatible RBC units approved by transfusion medicine physicians were safe with no acute or delayed hemolytic transfusion reactions seen. Almost half of patients receiving incompatible RBCs had red cell alloantibodies detected on pretransfusion testing, underscoring the need for careful evaluation and RBC unit selection in cases where incompatibility is detected.