Future Preventive and Therapeutic Targets for Transfusion-Related Acute Lung Injury

Transfusion-related acute lung injury (TRALI) has been the leading cause of transfusion-associated death for nearly a decade. Recent TRALI mitigation strategies focused on reduction of leukocyte antibodies in high volume plasma products appear to be successful in reducing TRALI events and deaths, but additional preventive measures are needed. Future possibilities include, screening of donors for neutrophil antibodies, processing of blood products to reduce or remove biologic response modifiers, and the more judicious use of blood. There are currently no specific TRALI therapies. The pathogenesis of TRALI and acute lung injury-acute respiratory distress syndrome (ALI-ARDS) is quite similar; both involving interactions of activated platelets, neutrophils, and pulmonary endothelium resulting in lung damage, capillary leak, and pulmonary edema. Greater understanding of these interactions and the key molecules involved will lead to development of potential new targets for therapy. In this review, future possible preventive measures to further reduce the occurrence of TRALI will be discussed, including TRALI caused by biologic response modifiers (BRMs), like bioactive lipids and sCD40L, which are not addressed by current preventive actions that only target leukocyte antibodies in high-volume plasma products. Insights already gained from studies of ALI-ARDS treatments will be summarized and discussed as possible therapeutic targets for treatment of patients experiencing TRALI.