Plasma Constituents Promote Endothelial Thromboinflammatory Dysfunction After Hemorrhagic Shock

Hemorrhagic shock (HS) following traumatic injury is hallmarked by innate immune activation, hypercoagulability, and thromboinflammatory complications. To date, the direct link between HS, injury severity, and endothelial cell (EC) contributions to thromboinflammation remains poorly understood. The goals of this study were to determine the impact of injury severity and HS on endothelial-mediated thromboinflammation and examine whether these changes increase the propensity for thrombosis.

Plasma from 89 male trauma patients, stratified by HS and injury severity, and 10 healthy subjects were assessed for inflammatory mediators by BioPlex. Human lung microvascular endothelial cells were exposed to patient plasma for 4 hours, after which surface thrombin generation was measured by calibrated automated thrombogram, and ribonucleic acid extracted for gene expression analysis. Plasma from mice that underwent sham or fixed-pressure HS was infused into naive mice, followed by inferior vena cava ligation to induce thrombosis. Thrombi were collected 24 hours later for histologic analysis.

Inflammatory mediators were highest in plasma from patients with severe injuries and HS. Human lung microvascular endothelial cells exposed to trauma patient plasma exhibited increased thrombin generation and thromboinflammatory gene expression, with a more pronounced effect in HS patients. Lastly, mice infused with HS plasma developed significantly larger thrombi with higher neutrophil infiltration and reduced EC thrombomodulin expression compared with that of those infused with sham plasma.

HS plasma amplifies endothelial-mediated inflammation and coagulation, which is driven, in part, by the presence of inflammatory mediators. HS plasma also increases the development of thrombosis in vivo . This study highlights mechanistic links between ECs, thromboinflammation, and postinjury complications.