Red blood cell alloimmunization mitigation strategies.

Hemolytic transfusion reactions due to red blood cell (RBC) alloantibodies are a leading cause of transfusion-associated death. In addition to reported deaths, RBC alloantibodies also cause significant morbidity in the form of delayed hemolytic transfusion reactions. These alloantibodies may also cause morbidity in the form of anemia, with compatible RBC units at times being unable to be located for highly alloimmunized patients, or in the form of hemolytic disease of the newborn. Thus, preventing RBC alloantibodies from developing in the first place, or mitigating the dangers of existing RBC alloantibodies, would decrease transfusion-associated morbidity and mortality. A number of human studies have evaluated the impact on RBC alloimmunization rates of providing partially phenotypically or genotypically matched RBCs for transfusion, and a number of animal studies have evaluated the impact of single variables on RBC alloimmunization. The goal of this review is to take a comprehensive look at existing human and animal data on RBC alloimmunization, focusing on strategies that may mitigate this serious hazard of transfusion. Potential factors that impact initial RBC alloimmunization, on both the donor and recipient sides, will be discussed. These factors include, but are not limited to, exposure to the antigen and an ability of the recipient's immune system to present that antigen. Beyond these basic factors, coexisting "danger signals," which may come from the donor unit itself or which may be present in the recipient, also likely play a role in determining which transfusion recipients may become alloimmunized after RBC antigen exposure. In addition, to better understanding factors that influence the development of RBC alloantibodies, this review will also briefly discuss strategies to decrease the dangers of existing RBC alloantibodies.