Platelet-neutrophil Interactions as a Target for Prevention and Treatment of Transfusion- related Acute Lung Injury

Axelle      Caudrillier; Mark      R. Looney

Abstract

Transfusion-related acute lung injury (TRALI) is a major cause of morbidity and mortality in transfused hosts and like other causes of acute lung injury, there is no effective pharmacologic treatment. The pathophysiology of TRALI is still being defined, but neutrophils have a major role in the pathogenesis of both human and experimental studies. Recently, MHC antibody-based experimental TRALI models have revealed that platelets sequester in the lung microvasculature and that platelet activation contributes to lung injury. Platelets, in general, have been increasingly implicated as major contributors to acute inflammation and injury in a variety of diseases. The role of platelets in TRALI may be through critical interactions with neutrophils and therapeutically this could present a target for pharmacologic intervention. Experimentally, aspirin pre-treatment of mice before TRALI is protective from acute lung injury and mortality. Other therapeutic interventions could include agents that uncouple neutrophils and platelets or prevent aggregation and activation, however targeting platelet activation in TRALI is complicated by the presence of bleeding as the indication for many transfusions. In conclusion, experimental studies are elucidating the role of platelets in acute lung injury and with this new understanding, clinical trials of anti-platelet agents should be considered.

Keywords: Platelets, neutrophils, transfusion-related acute lung injury, aspirin, transfused hosts, lung microvasculature, morbidity, mortality, platelet activation, anti-platelet agents