Recent insights into the mechanism of transfusion-related acute lung injury

Purpose of review This review summarizes the recent clinical and experimental literature on the pathogenesis of transfusion-related acute lung injury (TRALI), with a focus on mechanistic aspects. Recent findings Mechanisms by which leukocyte antibodies induce TRALI have been unraveled, including a multistep cascade for HLA class II-induced TRALI. Significant advances have also been made in the field of recipient-related factors that contribute to the development of TRALI, both in clinical and animal studies. In contrast, TRALI associated with the transfusion of blood components that do not contain antibodies is an emerging problem, especially because the relevance of mechanisms proposed earlier is questioned by the recent findings. New mechanisms need yet to be defined. The diversity of newly described factors contributing to TRALI demonstrates that a two-hit model falls too short to explain this complex syndrome and rather supports the previously proposed threshold model of TRALI. Summary Activated neutrophils are central in the pathophysiology of TRALI as their interaction with the lung endothelium causes capillary leak and pulmonary edema. Typically, numerous factors must act together in order to overcome a critical activation threshold of the neutrophil. At least one of these factors originates from a transfused blood component.