Transfusion-related (TR)-
acute lung injury (ALI) is the leading cause of transfusion-related morbidity and mortality. The pathogenesis of
TRALI is thought to be a "two hit"-entity: the "first hit" is (any) proinflammatory pulmonary condition (e.g.,
pneumonia,
sepsis or lung
contusion) resulting in activation of lung endothelium with sequestration of polymorphonuclear neutrophils - the "second hit" is provided by transfusion of a blood product. Either
antibodies against neutrophils are thought to be implicated in the activation of the sequestrated neutrophils, or bioactive
lipids (which accumulate during storage of blood products) induce the "second hit", finally resulting in
lung injury. Preventive measures do not prevent all
TRALI cases. Also,
TRALI is most probably underdiagnosed. In this review, we call for the development of therapeutic approaches for this potentially life-threatening disease. Several interventions which are beneficial in ALI and may also be beneficial in
TRALI are discussed. The application of these interventions requires the development of clinically relevant
TRALI animal models. We discuss the present
TRALI animal models and their shortcomings and propose future animal models, in which clinically relevant "first hits" can be applied, thereby imitating the complex clinical situation.