Assistant Professor Rutgers University Piscataway, New Jersey, United States
Background: Trauma induced coagulopathy (TIC) leads to excessive bleeding following severe injury, by preventing the formation of stable blood clots, increasing transfusion requirements and mortality. TIC has several phenotypes, with increased clot degradation (hyperfibrinolysis) being among the most lethal. However, the mechanisms causing each phenotype are poorly defined.
Aims: To determine the mechanisms and factors present during TIC and their impact on structure and stability of blood clots after trauma.
Methods: Platelet poor plasma (PPP) was supplemented with tissue plasminogen activator (tPA), tissue factor (TF) and saline dilution to model the hyperfibrinolysis, hyperactivation and hemodilution consistent with clinical TIC. We examined fibrin formation in this model of TIC (STIC) following clotting initiation with CaCl2 and thrombin. Samples were tested with confocal microscopy, optical turbidity, and viscoelastic testing to determine the turbidity, storage modulus, and structural properties.
Results: Across testing modalities STIC samples showed significantly higher storage modulus and optical density compared to controls at 600 seconds (p < 0.05, Fig. 1A-B). This was due in part to the polymerization rate being 9-16 times faster in STIC samples vs control samples (p < 0.001, Fig 1C-D). STIC samples had complete fibrin disintegration after 1800 seconds observed in confocal microscopy which corresponded with a complete loss of both structure and mechanical stability (Fig. 1A-B). To determine which component was the main cause of mechanical instability, we varied the individual factors described above and determined that hyperfibrinolysis most accurately generated the loss of mechanical and structural integrity (Fig. 1A-B). Addition of tranexamic acid, a fibrinolysis inhibitor, to the STIC samples caused a restoration of final mechanical properties compared to controls (Fig. 1A-B).
Conclusion(s): This in vitro plasma model demonstrated that each individual factor leads to unique alterations in the structure and stability of plasma clots, however hyperfibrinolysis is the main mechanistic driver of clot instability seen our simulated TIC clots.
