Platelets Play a Dual Role in the Pathophysiology of Transfusion-related Acute Lung Injury

Platelets are increasingly recognized as key regulators of inflammatory and immune responses, through their interaction with endothelium and immune cells. Therefore they might have a role in transfusion-related acute lung injury (TRALI), in which endothelial cells and neutrophils are the key players. In this study, by a classic TRALI animal model, combining a custom-designed system for intravital confocal microscopy of pulmonary microvasculature and a platelet tracking technique, we found that thrombin-activated platelets transfusion aggravated TRALI while resting platelets transfusion alleviated TRALI. Promoting endogenous platelets activation also aggravated TRALI while inhibiting endogenous platelets activation alleviated TRALI. Activated platelets interfered with the stability of endothelial barrier function while resting platelets modulated the activation of neutrophils. Anti-thrombin could alleviate TRALI, which was not reproduced upon anti-GPIIbIIIa or anti-P-selectin In conclusion, platelets might play a dual role (protective and pathogenic) in TRALI, the balance between the two roles is highly dependent on whether platelets are activated by thrombin or not. This might explain the conflicting results of previous researches studying the contribution of platelets in TRALI by platelet depletion technology, in which the induction of TRALI and the condition of animals were different, hence the state of platelets during TRALI was different. Moreover, anti-platelet-activation (such as anti-thrombin) might be a better approach than anti-activated-platelets (such as anti-P-selectin) to search for potential therapies in TRALI. Considering the involvement of thrombin-activated platelets in TRALI, anti-thrombin might be needed when blood component transfusion is performed.