Endothelial glycocalyx degradation predisposes for transfusion‐associated acute lung injury

Abstract

Transfusion‐associated acute lung injury (TRALI), a major cause of transfusion morbidity, arises from two events: an initial alteration in host susceptibility, followed by exposure to mediators in transfused blood products. We hypothesized that pulmonary endothelial glycocalyx degradation was a predisposing event in TRALI. We created a mouse model of TRALI, administering IV lipopolysaccharide (LPS) 2h prior to the administration of bioactive lipids (arachidonic acid, lysophosphatidylcholine) identified in stored human RBC units. Enzymatic cleavage of glycocalyx heparan sulfates similarly predisposed for TRALI, suggesting a role for glycocalyx degradation in host susceptibility to injury. Glycocalyx degradation could be detected in human blood via identification of heparan degradation products, defined by a heparinase effect of >; 15% on thromboelastography r‐time. Presence of circulating heparinoids was associated with a 50% risk (2/4) of plasma transfusion‐induced lung injury in bleeding patients with liver disease; patients with no circulating heparinoids had 0% risk (0/3). Endothelial glycocalyx degradation predisposes for TRALI and can serve as a biomarker for transfusion risk. NHLBI K08HL105538.