Hyperfibrinolysis Is Associated With Complement Activation Following Trauma.

Abstract

Background: Complement is activated after trauma, but the activation mechanism is unknown. Plasmin can directly activate C3 and C5, and four distinct fibrinolytic phenotypes have now been recognized after injury - hyperfibrinolysis, fibrinolysis shutdown, hypofibrinolysis, and non-pathologic/physiologic.

Objectives: We set out to investigate whether a relationship between complement activation and fibrinolysis was present in adult trauma patients (n=56).

Methods: Rapid and tPA-challenged thromboelastography (TEG) were performed in the emergency department with IRB approval, and plasma obtained for C3a, C4a, C5a, Ba, sC5b-9, Factor I, Factor H, active PAI-1, alpha-2 antiplasmin (A2AP), plasmin-antiplasmin complex (PAP), and tPA activity measurement via multiplex, ELISA and activity assays. Data were analyzed using ANOVA and Spearman's correlations. Significance was set at p<0.05.

Results: C3a and sC5b-9 were significantly higher in patients with hyperfibrinolysis than with physiologic or hypofibrinolysis (p<0.05). Elevations in C3a, C4a, and SC5b9, along with depletion of Factors H and I, were significantly associated with massive transfusion within 6 hours and post-injury death. There were significant positive correlations between multiple markers of fibrinolysis and complement activation markers, and significant negative correlations with Factors H and I. Significant negative correlations between fibrinolytic inhibitors and complement activation were also observed.

Conclusions: Our findings suggest that fibrinolysis may play a direct role in complement activation in trauma through plasmin-mediated cleavage of C3 and C5.