Pathogenesis of non-antibody mediated transfusion-related acute lung injury from bench to bedside

Transfusion of 35-Day Stored RBCs in the Presence of Endotoxemia Does Not Result in Lung Injury in Humans*

“…Several animal studies have demonstrated that maximally stored RBCs can function as a "second hit" and induce TRALI (10)(11)(12)(13)(14). Observational clinical studies, on the other hand, report conflicting data on this matter (10,(15)(16)(17). The use of allogeneic blood products in these studies hampers investigation of the isolated effect of storage time on lung injury.…”

“…The causative mechanism in non-antibody-mediated TRALI has not yet been identified, but increased storage time of cellcontaining blood products has been hypothesized to induce TRALI (10). Several animal studies have demonstrated that maximally stored RBCs can function as a "second hit" and induce TRALI (10)(11)(12)(13)(14). Observational clinical studies, on the other hand, report conflicting data on this matter (10,(15)(16)(17).…”

“…This resulted in the hypothesis of non-antibody-mediated TRALI. The causative mechanism in non-antibody-mediated TRALI has not yet been identified, but increased storage time of cellcontaining blood products has been hypothesized to induce TRALI (10). Several animal studies have demonstrated that maximally stored RBCs can function as a "second hit" and induce TRALI (10)(11)(12)(13)(14).…”

Gastrointestinal microbiota contributes to the development of murine transfusion-related acute lung injury

“…6,7 The second hit is subsequently conveyed by pathogenic antileukocyte antibodies or other biological response modifiers present in the transfused donor blood. 2,8 In the majority of the cases, human neutrophil antigen-or HLA-specific antibodies in the transfused blood are involved. 2 Using animal models of antibodymediated TRALI, it has become clear that neutrophils (polymorphonuclear cells [PMNs]) are the major effector cells in TRALI.…”

Low levels of interleukin-10 in patients with transfusion-related acute lung injury

“…Transfusion related acute lung injury (TRALI) is the leading cause of transfusion-related fatalities (FDA Report 2016) (1) and is characterized by the acute onset of respiratory distress within 6 hours following blood transfusion (2,3). The clinical diagnosis is confirmed in case of newly developing acute respiratory distress: PaO 2 /FiO 2 ratio (ratio of arterial oxygen partial pressure to fractional inspired oxygen) <300 mmHg or arterial oxygen saturation <90% at room air; newly developed or worsened bilateral pulmonary infiltrates indicative of pulmonary edema on chest X-ray; emergence of all symptoms within 6 hours upon blood transfusion and exclusion of cardiac ischemia and transfusion associated circulatory overload (TACO).…”