Abstract
Trauma-induced coagulopathy (TIC) worsens patient outcomes and increases transfusion requirements. Resuscitation strategies following injury have evolved to improve clinical outcomes. However, the mechanisms by which these strategies impact coagulation and whether they restore native coagulation in the presence of TIC are poorly understood. We compared coagulation parameters and vital signs of patients who did (n = 26) and did not (n = 37) receive transfusion following injury. Transfusion products administered to patients were recreated in vitro, and their influence on a simulated model of TIC was measured. Optical turbidity, rheology, thromboelastography, and confocal microscopy were used to evaluate the clotting properties of platelet-poor plasma and whole blood models of hypocoagulable and hypercoagulable TIC. Transfusion models were supplemented with Saline, Plasma, Fibrinogen Concentrate, or Red Blood Cells (RBC). Transfused patients exhibited faster time to mortality, clot stiffness, and fibrinogen concentration compared to non-transfused patients. In the simulated transfusion model, saline reduced clot stiffness, increased fibrinolytic rate, and affected network structure. Plasma increased clot stiffness and density, and reduced fibrinolysis. Fibrinogen concentrate enhanced clot stiffness in plasma-based models but also increased fibrinolytic rate. RBC supplementation had variable impacts, causing weaker blood clots and accelerated fibrinolysis in hypocoagulable models, but delayed fibrinolysis in hypercoagulable models. Resuscitation products exert context-dependent effects on clot formation and breakdown that may not restore hemostasis during TIC. Saline induced dilutional hypocoagulability and increased clot failure risk, plasma enhanced clot stability, fibrinogen improved clot formation, and RBCs exerted endogenous coagulation-specific effects. These results support coagulation phenotyping to guide targeted transfusion strategies.