Analysis of cutoffs for screening sensitized blood donors for HLA alloantibodies using a cytometric microbead assay.

Background: Cytometric-based microbead assays for HLA alloantibodies may be effective tools for transfusion-related acute lung injury (TRALI) risk reduction. However, the optimal cutoff for donor screening is unclear.

Study Design And Methods: To optimize the screening test cutoff in sensitized donors, sera were screened with a cytometric microbead assay. Confirmatory testing was performed on samples with a normalized background (NBG) ratio of 2.4 or more.

Results: Sera with a NBG of 2.4 to 9.9 had positive predictive values (PPVs) of 78.2% (95% confidence interval [CI], 67.8%-86.0%) and 71.1% (95% CI, 56.5%-82.4%) for Class I and II antibodies, respectively. Sera with a NBG of 10 or more had PPVs of 98.9% (95% CI, 93.3%-100%) and 99.1 (95% CIs, 94.7%-100%) for Class I and II, respectively. The percent panel-reactive antibody (PRA) of confirmed HLA alloantibodies from sera with a NBG of 2.4 to 9.9 was 29.3±17% (mean±standard deviation) for Class I and 22.3±16.7% for Class II, but for antibodies from sera with a NBG of 10 or more the PRAs were 65.3±24.0 and 64.1±25.2% for Class I and II, respectively (p<0.00001). Serial dilution studies comparing the screening test with antiglobulin-enhanced lymphocytotoxicity suggested that NBG correlated with antibody titer. In our center, deferral for prior pregnancy or transfusion would result in loss of 28.8% of apheresis platelet (PLT) donors. Using the screening test at a cutoff of 2.4 or more or 10 or more would reduce the fraction of donors lost to 12.7 or 8.0%, respectively.

Conclusions: A screening cutoff of 10 or more predicts HLA alloimmunization in sensitized donors and is associated with higher PRAs and titers. Implementation of this cutoff may reduce TRALI risk while limiting unnecessary deferral of PLT donors.