Establishing assay cutoffs for HLA antibody screening of apheresis donors

Abstract

BACKGROUND-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 donors. However, if screening assay cutoffs are too sensitive, donation loss may adversely impact blood availability.

Transfusion-related acute lung injury: incidence and risk factors

“…further reduce TRALI risk, our clinical evidence supports consideration of screening donors for strong HLA class II antibodies 15 and the development of high-throughput GIFT methods to screen for antibodies to known and unknown human neutrophil antigens. Importantly, reduction of modifiable patient risk factors should also reduce the risk for developing TRALI.…”

“…After testing multiple assay thresholds (in models that did not include the cognate HLA class II variable), we found that a larger volume of strong anti-HLA-class II (NBG ratio Ͼ 27.5) increased risk (OR ϭ 1.92 per 100 mL, 95% CI, 1.08-3.4, P ϭ .03), a threshold equivalent to greater than 5 SDs in a cohort of nontransfused males. 15 However, similar to the specific anti-HLA antibodies, the volume of weak anti-HLA-class II positive on the screening test (NBG ratio, 2.2-27.5) was not associated with risk (OR ϭ 0.81 per 100 mL, 95% CI, 0.34-1.93, P ϭ .63), and the volume of anti-HLAclass I did not appear to increase risk, even for strong antibody (NBG ratio Ͼ 59.3, OR ϭ 0.98 per 100 mL, 95% CI, 0.46-2.1, P ϭ .97). In risk factor analysis, total quantities of CD11b up-regulation (% positive cells ϫ plasma volume) in all units received by a patient were a statistically significant risk factor in univariate analysis (Table 9) but not in multivariate analysis.…”

Ultraviolet light‐based pathogen inactivation and alloimmunization after platelet transfusion: results from a randomized trial

“…The data were first analyzed using the manufacturer's recommended, highly sensitive cutoff commonly used in tissue transplant to detect antibodies to potential organ donor antigens: an NBG ratio of 2.2. The data also were analyzed in secondary analyses using NBG ratios of the mean plus three or five standard deviations of a log‐transformed distribution of values for plasma samples for greater than 1000 men who had not received transfusion . These values were 10.7 and 59.2, respectively, for HLA Class I and 6.8 and 27.4, respectively, for HLA Class II.…”

Transfusion Reactions

“…53,54 The decrease in TRALI observed after implementation of such programs support the effectiveness of this approach. To further reduce TRALI risk in female plasma-rich components, clinical evidence support the suggested screening for strong anti-HLA-Class II in platelet donors 55 and the development of high-throughput GIFT methods to screen for known and unknown human neutrophil antigens. 8 In addition, reduction of modifiable patient risk factors should also reduce the risk for developing TRALI.…”