A threshold model for the susceptibility to transfusion-related acute lung injury

Transfusion-related acute lung injury (TRALI) is a serious, often life-threatening pulmonary transfusion reaction characterized by non-cardiogenic lung oedema, hypoxemia and respiratory distress in temporal association with blood transfusion. The critical mechanism in TRALI is the sudden increase in permeability of the pulmonary endothelium and the subsequent, often extensive shift of fluid into the alveolae. The rapid clinical recovery seen in most patients makes it likely that this is a temporary phenomenon. Reactive oxygen species released by neutrophils or other cells are attractive candidate mediators of this process. There is experimental and clinical evidence that several pathways can induce barrier breakdown in TRALI, a concept known as the threshold model of TRALI. Surprisingly, neutrophils may not always be required. Other cells may play a role as multipliers or attenuators of TRALI, depending on recipient-related and transfusion-related factors involved. This review will summarize recent findings on pathophysiology, with a focus on newly discovered or disenchanted recipient-related and transfusion-related risk factors for TRALI and will present the threshold model of TRALI as a unifying concept on how TRALI develops.