TRALI Pathophysiology.

Abstract SCI-48

Transfusion related acute lung injury (TRALI) is clinically defined as the new onset of acute lung injury within 6 hours of a transfusion. In TRALI a transfusion activates neutrophils leading to pulmonary leukostasis, endothelial damage, capillary leak and pulmonary edema. A number of elements (bioactive lipids, sCD40L, and leukocyte antibodies) found in blood products can active neutrophils and are risk factors for TRALI. Bioactive lipids and sCD40L accumulate in both stored red cell and platelet components. Leukocyte antibodies are most often found in blood components collected from women alloimmunized during pregnancy. A number of animal and in vitro models have shown that neutrophils activated by leukocyte antibodies cause pulmonary leukostatsis, endothelial damage and capillary leak. Far more blood components contain these TRALI factors than cause TRALI suggesting that additional patient, clinical, or blood component factors are required for the development of TRALI. For example, neutrophil-specific antibodies cause reactions in, at most, 25% of transfusion recipients. Animal models and in vitro studies have found that blood component factors are more likely to induce lung injury if the neutrophils and/or pulmonary endothelial cells are primed or activated. Endothelial cells can be primed by endotoxin and neutrophils can be primed by bioactive lipids and sCD40L. The priming of neutrophils and /or endothelium results in the tight adhesion of neutrophils to endothelial cells and enhances endothelial cell injury Between neutrophil and HLA Class I and II antibodies, neutrophil antibodies are most potent at initiating TRALI and HLA Class I antibodies are least potent. HLA Class I antigens are expressed by platelets, lymphocytes, monocytes and soluble HLA Class I antigens are present in plasma. These sources of Class I antigens likely compete with neutrophils for transfused Class I antibodies and may render them less effective at initiating TRALI than neutrophil-specific or HLA Class II antibodies. Some evidence suggests that HLA Class I antibodies induce TRALI by binding to pulmonary endothelium and activating neutrophils through their Fc portion. Class II antibodies may initiate TRALI by binding to monocytes and stimulating cytokine release. In summary, TRALI is the result of patient and blood component factors which lead to neutrophil activation and endothelial cell damage and capillary leak. Most cases likely require the confluence of multiple factors to form a “perfect inflammatory storm” which leads to significant lung injury.