Fibrin degradation products enhance plasmin activity and contribute to fibrinolysis during simulated trauma-induced coagulopathy

OBJECTIVE: Fibrinolysis is an important component of trauma-induced coagulopathy (TIC) that is strongly associated with early mortality after injury. Yet, the mechanisms driving excessive fibrinolysis remain incompletely understood. We hypothesized that fibrin degradation products (FDPs) known to become elevated in the blood after trauma can actively contribute to TIC by promoting disordered clot formation and enhanced plasmin activity. METHODS: Purified FDPs, fragments X, D, E, and D-dimer, were titrated into normal human plasma in vitro at physiologically relevant concentrations under normal and simulated TIC conditions. Rotational thromboelastometry (ROTEM) was used to assess their effects on clot initiation, formation, firmness, and lysis. Thrombin generation assays (TGA) and plasmin generation assays (PGA) were performed to measure enzymatic activity in the presence of each FDP. Key parameters included clotting time (CT), α-angle, maximum clot firmness (MCF), lysis index at 45 minutes (LI-45), maximum lysis (ML), time to peak plasmin activity, PGA slope and peak plasmin concentration. RESULTS: Fragments D, X, and D-dimer increased clot lysis by ROTEM under TIC-like conditions. D-dimer and D fragments significantly accelerated plasmin generation judged by shortening PGA peak time, and increasing PGA slope and concentration, whereas thrombin generation was not different across all groups. CONCLUSIONS: Individual FDPs, including fragments D, X, and D-dimer, can contribute to TIC by increasing plasmin activity. Further studies in whole blood and trauma patient samples are warranted.