Why can a positive crossmatch prevent a donor-recipient transplant from taking place?

A positive crossmatch indicates that the recipient’s serum contains preexisting antibodies that react against the potential donor’s lymphocytes. This test is performed as a final safety precaution before a transplant to identify if the recipient has been previously sensitized to the donor's antigens through events such as prior transplants, blood transfusions, or pregnancy.12

When a recipient has these preexisting antibodies, the immune system can launch an immediate, antibody-mediated rejection of the transplanted tissue. Unlike cell-mediated rejection, which develops over days or months and may be managed with immunosuppression, antibody-mediated rejection occurs rapidly—often within minutes or hours—and is generally irreversible. Because this reaction poses an immediate and severe threat to the viability of the graft, a positive crossmatch typically contraindicates the transplant, preventing the surgery from proceeding.21