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BACKGROUND: Platelet (PLT) transfusions can induce humoral and cellular alloimmunity. HLA antibodies can render patients refractory to subsequent transfusion, and both alloantibodies and cellular alloimmunity can contribute to subsequent bone marrow transplant (BMT) rejection. Currently, there are no approved therapeutic interventions to prevent alloimmunization to PLT trans-fusions other than leukoreduction. Targeted blockade of T-cell costimulation has shown great promise in inhibiting alloimmunity in the setting of transplantation, but has not been explored in the context of PLT transfusion. STUDY DESIGN AND METHODS: We tested the hypothesis that the costimulatory blockade reagent CTLA4-lg would prevent alloreactivity against major and minor alloantigens on transfused PLTs. BALB/c (H-2d) mice and C57BL/6 (H-2b) mice were used as PLT donors and transfusion recipients, respectively. Alloanti-bodies were measured by indirect immunofluorescence using BALB/c PLTs and splenocytes as targets. BMTs were carried out under reduced-intensity conditioning using BALB.B (H-2b) donors and C57BL76 (H-2b) recipi-ents to model HLA-identical transplants. Experimental groups were given CTLA4-lg (before or after PLT trans-fusion) with control groups receiving isotype-matched antibody. RESULTS: CTLA4-lg abrogated both humoral alloim-munization (H-2d antibodies) and transfusion-induced BMT rejection. Whereas a single dose of CTLA4-lg at time of transfusion prevented alloimmunization to sub-sequent PLT transfusions, administration of CTLA4-lg after initial PLT transfusion was ineffective. Delaying treatment until after PLT transfusion failed to prevent BMT rejection. CONCLUSIONS: These findings demonstrate a novel strategy using an FDA-approved drug that has the potential to prevent the clinical sequelae of alloimmuni-zation to PLT transfusions. [ABSTRACT FROM AUTHOR]

Unique issues in blood donation and blood transfusion regarding African Americans (AA) in the United States span the donation process, manufacturing of products, and hospital transfusion service. As AAs become a growing population, a constant supply of blood donated by AAs is necessary to support this growth. Nationally, AAs are underrepresented in blood collection, which may be secondary to AAs having higher rates of anemia and other deferrable conditions or unique motivators as well as other barriers to blood donation. When investigating blood transfusion practices, blood utilization for different races and ethnicities is unknown. AAs may receive more red blood cell (RBC) transfusions because they have a higher proportion of diseases that require transfusion. Patients with sickle cell disease are at increased risk of RBC alloimmunization likely due to the predominance of RBC units from white donors in the existing blood supply, but it is not known if all AA recipients experience increased alloimmunization rates compared with whites. In conclusion, there is a need to increase donation by AAs, which can only be achieved by conducting studies to understand racial differences in donor recruitment and to better understand blood utilization and adverse events as a factor of race and ethnicity.