Establishing assay cutoffs for HLA antibody screening of apheresis donors

Abstract

BACKGROUND: Transfusion‐related acute lung injury (TRALI) is the leading cause of transfusion‐related deaths. Donor HLA antibodies have been implicated in TRALI cases. Blood centers are implementing TRALI risk reduction strategies based on HLA antibody screening of some subpopulations of ever‐pregnant apheresis platelet (PLT) donors. However, if screening assay cutoffs are too sensitive, donation loss may adversely impact blood availability. STUDY DESIGN AND METHODS: Pregnancy history and HLA antibody screening and single‐antigen bead data from blood donors in the Retrovirus Epidemiology Donor Study‐II Leukocyte Antibody Prevalence Study were evaluated for correlations between assay screening values, HLA antibody titer, and number of HLA antigen specificities. The probabilities of matching a cognate antigen in a recipient were calculated and examined in association with total number of specificities observed and screening values. The relative impact of imposing various screening assay cutoffs or pregnancy stratification was examined in relation to detection of HLA antibody–reactive donations and loss of donors and donations. RESULTS: We provide evidence that higher HLA antibody screening assay values are associated with maintaining higher screening signals upon dilution and an increased breadth of specificities compared with lower screening values; the latter correlated with an increased risk of a cognate antigen match in potential recipients. Depending on the TRALI risk reduction strategy used, the potential loss of donations ranged between 0.9 and 6.0%. CONCLUSION: This analysis should enable blood centers to decide upon a TRALI risk reduction strategy for apheresis PLTs that is consistent with how much donation loss the blood center can tolerate.