Transfusion-related acute lung injury investigation insights

Background From 2005 to 2009 transfusion-related acute lung injury (TRALI) has maintained its ranking as the number one cause of transfusion-related fatalities reported to the FDA. This confirms that TRALI remains a serious and potentially fatal transfusion complication. As over 80% of TRALI events have been attributed to donor derived leucocyte antibodies the detection and management of donors with these antibodies is crucial to reducing the TRALI risk. Objective Because blood is a precious medical commodity in limited supply, it would be more effective to exclude only those donors with a risk of triggering TRALI substantiated by objective laboratory evidence (i.e. implicated). This would allow implicated donors to be confidently excluded and would allow other donors only clinically associated with TRALI to be reassessed for continuing to donate. Therefore, the design of an effective and objective TRALI laboratory investigation strategy has to be based on current knowledge of the mechanism of antibody mediated TRALI. Discussion Leucocyte antibodies in the transfused blood product are thought to activate neutrophils in the pulmonary microvasculature. The by-products of neutrophil activation (e.g. reactive oxygen species and enzymes) consequently cause injury to the pulmonary microvasculature resulting in respiratory distress. There is strong evidence for the role of neutrophil reactive antibodies to human neutrophil antigen (HNA)-3a and human leucocyte antigen (HLA)-A2 in serious TRALI events. HLA Class II antibodies have also been implicated and they are thought to activate monocytes, which subsequently activate neutrophils. Neutrophils, which express human neutrophil antigens (HNA) and HLA Class I, are thus key effector cells in TRALI injury. Because of the pivotal role of neutrophils, effective TRALI investigations must include well validated neutrophil assays such as the granulocyte immunofluorescence test (GIFT) and granulocyte agglutination test (GAT). This article will discuss: – TRALI investigation strategy, – assays for detection of antibodies to HNA and HLA, – how to differentiate associated from implicated donors, – and provide thoughts on the remaining 20% of TRALI events (i.e. non-immune mediated).