Abstract

Trauma with hemorrhagic shock causes massive tissue plasminogen activator release, plasmin generation, and hyperfibrinolysis. Tranexamic acid (TXA) has recently been used to treat bleeding in trauma by preventing plasmin generation to limit fibrinolysis. Trauma patients also have increased complement activation that correlates with mortality and organ failure, but the source of activation is not clear, and plasmin has recently been shown to efficiently cleave C3 and C5 to their activated fragments. We hypothesized that trauma patients in hemorrhagic shock with hyperfibrinolysis on thromboelastography (TEG) LY30 would have increased complement activation at early time points, as measured by soluble C5b-9 complex, and TXA would prevent this. Plasma samples were obtained from an unrelated, previously performed IRB-approved prospective randomized study of trauma patients. Three groups were studied with n = 5 patients in each group: patients without hyperfibrinolysis (TEG LY30 < 3%) (who therefore did not get TXA), patients with hyperfibrinolysis (TEG LY30 > 3%) who did not get TXA, and patients with hyperfibrinolysis who were then treated with TXA. We found that patients who did not receive TXA, regardless of fibrinolytic phenotype, had elevated soluble C5b-9 levels at 6 h relative to emergency department levels. In contrast, all five patients with initial TEG LY30 more than 3% and were then treated with TXA had reduced soluble C5b-9 levels at 6 h relative to emergency department levels. There were no differences in PF1 + 2, Bb, or C4d levels between groups, suggesting that coagulation and complement activation pathways may not be primarily responsible for the observed differences.