Transfusion-related acute lung injury (TRALI) is the serious complication of transfusion of blood products that is characterized by the rapid onset of excess fluid in the lungs. It can cause dangerous drops in the supply of oxygen to body tissues. Although changes in transfusion practices have reduced the incidence of TRALI, it was the leading cause of transfusion-related deaths in the United States from fiscal year 2008 through fiscal year 2012.
Signs and symptoms It is often impossible to distinguish TRALI from acute respiratory distress syndrome (ARDS). The typical presentation of TRALI is the sudden development of shortness of breath, severe hypoxemia (O2 saturation <90% in room air), low blood pressure, and fever that develop within 6 hours after transfusion and usually resolve with supportive care within 48 to 96 hours. Although low blood pressure is considered one of the important signs for diagnosing TRALI, in some cases high blood pressure can occur. Delayed TRALI occurs 6 to 72 hours after transfusion completion. It is associated with a higher rate of mortality.
Cause 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, with transfused antibodies shown to bind antigens expressed on pulmonary endothelial cells to initiate acute inflammation in the lungs. Women who are multiparous (have carried more than one pregnancy to viable gestational age) 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 proposed mechanism for non-antibody-mediated TRALI involves the accumulation of bioactive lipids in stored blood components (red cells, platelets, or plasma) that are capable of priming neutrophils. TRALI is typically associated with plasma products such as fresh frozen plasma. TRALI can also occur in recipients of packed red blood cells, whether adult or pediatric patients. Due to the higher risk of TRALI resulting from donations by females, the AABB (formerly the American Association of Blood Banks) has recommended that those blood components with a high volume of plasma not be used for transfusion, but for further processing into other therapeutic products. To mitigate the risk of TRALI, female donors are excluded from fresh frozen plasma donation in Germany as of 2009 if they have a history of pregnancy and there are no HLA/HNA screening results available, which has resulted in a significant reduction of TRALI reports.
Pathophysiology In TRALI, first-hit risk factors include long-term excessive alcohol use, shock, liver surgery, current smoking, higher peak airway pressure while undergoing mechanical ventilation, positive intravascular fluid balance, low levels of interleukin-10, and systemic inflammation. Systemic inflammation may be reflected in the plasma cytokine profiles but also via increased levels of C-reactive protein (CRP), an acute-phase protein that rapidly increases during acute infections and inflammation and is widely used clinically as a biomarker of inflammation. CRP has been shown to be elevated in TRALI patients and, in a mouse model, to functionally enable the first hit in the development of TRALI by increasing the accumulation in the lungs of a neutrophil homologous to interleukin-8. Another factor that can predispose patients to TRALI is pre-existing lung injury, which causes white blood cells to localize in the lungs' blood vessels. The second hit in TRALI may be conveyed by anti-leukocyte antibodies or other factors present in the transfusion product. In approximately 80% of cases, anti-HLA class I or II or anti-HNA antibodies are implicated as involved in triggering TRALI, although that figure may be even higher depending on the detection methods used. In the remaining 20% of TRALI cases, non–antibody factors or biological response modifiers are suggested to contribute the second hit, and these may possibly include lipid mediators, extracellular vesicles, and aged blood cells.
Diagnosis
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