Abstract P33: A Computational Model of In Vivo Trauma Induced Coagulopathy
Objective: The PULSE initiative identified prevention of diffuse coagulopathies to be a priority in resuscitation science. Trauma Induced Coagulation (TIC) is a significant complication of trauma involving the complex nonlinear interplay of the coagulation and inflammation system (CIS). Its complexity poses significant challenges for systematic clinical study. Modeling via computational approaches may prove to be a valuable adjunct. We developed a model of TIC using a 2-D Agent Based Model (ABM).
Methods: A 2-D particle system was developed in which particles move and interact on a discrete spatial grid composed of ‘cells’. The particles of the system are cells (endothelial, WBC, platelets), reactants, enzymes, and reaction products. The number of ‘cells’ used in the simulations is 1,000,000 with a coagulation factor density of 16%. The particles’ actions are determined by a set of rules derived from coagulation kinetics and cell behaviors. The system is designed to model a blood vessel in vivo including blood flow. The model is perturbed by alterations in systemic variables (temperature, pH, coagulation factor concentration, oxygenation).
Results: The effects of temperature, pH, and coagulation factor dilution were synergistic on the model resulting in increased INR values ranging form 1.5 to 7.76. A state of anti-coagulation and hyperfibrinolysis existed independent of temperature and pH. Endothelial cell activation from hypovolemia resulted in the increased expression of TM, TFPI, and tPA with a concomitant decrease in PAI. This resulted in a state of anticoagulation from the diversion of thrombin to the activation of PC (by binding to thrombin) combined with increased TFPI. Increased levels of tPA combined with decreases in PAI result in a state of hyperfibrinolysis that dissolves any clot formed in the anti-coagulation environment.
Conclusion: The simulation indicates that the effects of trauma on the CIS can be readily simulated. The ABM successfully modeled TIC seen in vivo due to endothelial cell activation from hypoperfusion as supported by the literature. The ABM will be used to target mediator levels for clinical verification as well as to develop preclinical and clinical testing of therapies that may modulate the CIS to enhance outcomes.