AABB2025: Assessing Clinical Outcomes Following Transfusion of Crossmatch-Incompatible RBCs

Crossmatch incompatible red blood cells (RBCs) may pose an increased risk for transfusion reactions, including acute and delayed hemolysis, according to new data presented during the “Non-Infectious Hazards of Blood Transfusion” oral abstract session on Sunday. David Boamah, MHS, MD, second year resident physician at New York-Presbyterian Hospital/Weill Cornell Medicine, presented findings on the etiology and outcomes of crossmatch incompatible transfusions, highlighting the lack of modern studies assessing the clinical impact associated with these cases.  

Boamah opened his presentation by highlighting the role of pre-transfusion testing in minimizing transfusion-related risks. Standard procedures include ABO/Rh typing, review of the patient’s transfusion history, antibody screening and identification and crossmatching to ensure compatibility between donor and recipient blood.  

“The crossmatch remains a cornerstone of pre-transfusion testing,” Boamah explained. “It helps confirm that a selected red blood cell unit will not result in harmful serologic incompatibility.” 

Boamah and his colleagues conducted a retrospective study of non-emergent incompatible transfusions using the institution’s incompatible crossmatch consult system. Each consult outlined why the incompatible unit was selected and confirmed that transfusion was deemed appropriate by transfusion medicine specialists. Only RBC units approved as safe for issue by the transfusion medicine physician and transfused to patients were included in the study.  

Between May 2022 and December 2024, 13,461 serologic crossmatches were performed, resulting in 144 incompatible crossmatch consults for 53 patients. Of the 144 incompatible units transfused, 95 (66%) were prophylactically matched for common red cell antigens. He shared that 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. The average age of the patients was 67.3 years old, and the majority of the consults occurred in the hematology/oncology department.  

The findings showed that 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. The primary diagnoses among the patients included lymphocytic leukemias with miscellaneous diagnoses including sepsis and cerebral edema. Boamah pointed out that transfusion reactions were rare and not associated with incompatibility.  

“Our findings show that non-emergent transfusion of crossmatch-incompatible red blood cells can be performed safely when appropriately justified,” Boamah concluded. “Understanding the causes of incompatibility, particularly in patients on monoclonal antibody therapy, is key to ensuring both safety and efficiency in transfusion practice.”