Transfusion-related acute lung injury (TRALI) is a subcategory of acute lung injury (ALI). As such, there are many similarities between the syndromes, both clinically and pathophysiologically. Pulmonary changes in fibrin turnover have emerged as a hallmark of ALI, thereby initiating studies investigating the potential of therapeutic interventions aimed at ameliorating this so-called pulmonary coagulopathy. Enhanced coagulation and impaired fibrinolysis are probably also important features of TRALI. In particular, platelets play an important role in mediating injury during a TRALI reaction. In this narrative review, the evidence of the role of coagulopathy and platelet activation in TRALI is discussed. Given that host risk factors for acquiring TRALI have been identified and that there is a time frame in which a preventive strategy in patients at risk for TRALI can be executed, preventive strategies are suggested. In this review, we discuss potential preventive anticoagulant interventions.