The focus of the grant is to investigate red blood cell alloimmunization risk using the REDS-III databases. Red blood cell (RBC) alloimmunization is a leading cause of morbidity and mortality in transfusion and pregnancy settings, resulting in hemolytic reactions and other adverse sequelae such as hemolytic disease of the fetus and newborn. Alloimmunization occurs in up to 40% of some patient populations, including those with sickle cell disease (SCD); rates in patients with myelodysplastic syndrome, thalassemia major, and autoimmunity are also high. Most studies of RBC alloimmunization to date have been observational, retrospective, and single-center, limited to descriptions of incidence/prevalence rates and to recipient characteristics associated with alloimmunization. In this study, the team will investigate blood donor and blood unit contributions to RBC alloimmunization risk.