Transfusion-related acute lung injury

Transfusion-related acute lung injury (TRALI) is a serious blood transfusion complication characterized by the acute onset of non-cardiogenic pulmonary edema following transfusion of blood products. Transfusion-related acute lung injury (TRALI) is a serious blood transfusion complication characterized by the acute onset of non-cardiogenic pulmonary edema following transfusion of blood products. Although the incidence of TRALI has decreased with modified transfusion practices, it was the leading cause of transfusion-related deaths in the United States from fiscal year 2008 through fiscal year 2012. It is often impossible to distinguish TRALI from adult respiratory distress syndrome. The typical presentation of TRALI is the sudden development of dyspnea, severe hypoxemia (O2 saturation <90% in room air), hypotension, and fever that develop within 6 hours after transfusion and usually resolve with supportive care within 48 to 96 hours. Although hypotension is considered one of the important signs in diagnosing TRALI, hypertension can occur in some cases. The cause of TRALI is currently not fully understood. 80-85% of cases are thought to be immune mediated. Antibodies directed toward human leukocyte antigens (HLA) or human neutrophil antigens (HNA) have been implicated. Women who are multiparous (conceived more than one child) develop these antibodies through exposure to fetal blood; transfusion of blood components obtained from these donors is thought to carry a higher risk of inducing immune-mediated TRALI. Previous transfusion or transplantation can also lead to donor sensitization. To be at risk of TRALI via this mechanism, the blood recipient must express the specific HLA or neutrophil receptors to which the implicated donor has formed antibodies. A two-hit hypothesis has been suggested wherein pre-existing pulmonary pathology (i.e. the first-hit) leads to localization of neutrophils to the pulmonary microvasculature. The second hit occurs when the aforementioned antibodies are transfused and attach to and activate neutrophils, leading to release of cytokines and vasoactive substances that induce non-cardiac pulmonary edema. A non-immune mechanism has been studied and proposed by Silliman, involving the accumulation of bioactive lipids in stored blood components (red cells, platelets, plasma) that possess neutrophil priming capabilities. TRALI is typically associated with plasma products such as FFP. TRALI can also occur in recipients of packed red blood cells both in adult and pediatric patients. The AABB (formerly the American Association of Blood Banks) recommended on 11/03/2006 in association bulletin 06-07 that blood banks use high plasma volume components from female donors for further manufacturing instead of transfusion due to the higher risk of TRALI. 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. TRALI is defined as an acute lung injury that is temporally related to a blood transfusion; specifically, it occurs within the first six hours following a transfusion. It is typically associated with plasma components such as platelets and fresh frozen plasma, though cases have been reported with packed red blood cells since there is some residual plasma in the packed cells. The blood component transfused is not part of the case definition.