Cumulative Donor-Specific Antibody Threshold Predicts Platelet Transfusion Response in HLA-Alloimmunized Patients.

Up to a third of multiply transfused patients with hemato-oncologic conditions develop immune-mediated platelet transfusion refractoriness. Yet factors that influence post-transfusion platelet corrected count increments (CCI) in patients with human leukocyte antigen (HLA)-alloimmune platelet transfusion refractoriness remain less well elucidated. Recent advances in HLA antibody characterization using fluorescent bead-based platforms enable the study of donor-specific antibody (DSA) avidity (as measured by mean fluorescence intensity, MFI) and its impact on HLA-alloimmune platelet transfusion refractoriness. In this large retrospective study of 2,012 platelet transfusions among 73 HLA-alloimmunized patients, we evaluated the impact of cumulative HLA DSA-MFI alongside other donor, platelet component, and patient characteristics on CCI at 2 and 24-hours post-transfusion. As part of a quality improvement initiative, we also developed and tested a computerized algorithm to optimize donor-recipient histocompatibility based on cumulative DSA-MFI and sought other actionable predictors of CCI. In multivariate analyses, cumulative HLA DSA-MFI ≥ 10,000, major/bidirectional ABO-mismatch, splenomegaly, transfusion reactions, and platelet storage in additive solution negatively impacted 2-hour but not 24-hour post-transfusion CCI. The DSA-MFI threshold of 10,000 was corroborated by greater antibody-mediated complement activation and significantly more CCI failures above this threshold, suggesting the usefulness of this value to inform "permissive platelet mismatching" and to optimize CCI. Further, DSA-MFI decreases were deemed feasible by the computer-based algorithm for HLA-platelet selection in a pilot cohort of 8 patients (122 transfusions) evaluated before and after algorithm implementation. Where HLA-selected platelets are unavailable, ABO-identical/minor-mismatched platelet concentrates may enhance 2-hour CCI in heavily HLA-alloimmunized patients with platelet transfusion refractoriness.