Transfusion Related Acute Lung Injury - Pathophysiology

Pathophysiology

The precise mechanisms of the capillary leak syndrome in TRALI have not been fully determined, but two main hypotheses have been proposed. One involves white cell antibody-mediated TRALI and the other cytokine-mediated TRALI. The former suggests that TRALI is often a result of infusion of antibodies to HLA class I or class II or human neutrophil antigens (HNAs). Following transfusion, these antibodies react with neutrophils in the pulmonary microvasculature. Activated neutrophils damage the endothelium. Vascular leakage into the alveolar space with pulmonary edema ensues. In 90 percent of reported cases, antibodies were present in the donor plasma; in 10 percent of the cases antibodies were present in the recipient plasma. The second hypothesis suggests that neutrophils accumulate and are primed in the patient's pulmonary microvasculature as a result of preexisting systemic inflammation. Activation of these neutrophils by lipids or other mediators, such as CD40L, which accumulate in cellular blood components during storage, contributes to endothelial damage in susceptible patients, leading to vascular leaks and pulmonary edema. Because 20 percent of blood components contain HLA antibodies yet TRALI is relatively uncommon, it is conceivable that additional factors play a role in the development of TRALI.