Computational Analysis of Acute Traumatic Coagulopathy

Over many millions of years of vertebrate evolution, our blood has developed a robustsystem to patch injuries and stop hemorrhage. However, sometimes a serious injury canderail this system completely. Acute Traumatic Coagulopathy (ATC) is a condition thatarises often in major trauma that makes the cessation of bleeding an uphill battle, evenwith the help of modern medicine. Confounding properties of ATC include inefficacy oftransfusion treatment, tissue specific hemostasis and time-sensitive efficacy of tranexamicacid. In addition, the mechanism or mechanisms behind ATC are still unresolved. Dueto the complex nature of the coagulation system and limited methods for obtaining data,it is difficult to make progress with empirical experiments alone. Computational modelsoffer a way to leverage our current understanding of coagulation to unravel the mysteryof how ATC could occur.In this thesis, we use computational models to propose a mechanism for ATC throughhyperfibrinolysis and provide a model that can be used to test other hypotheses. We proposethat the fibrinolytic response, specifically the release of tissue-plasminogen activator(t-PA), within vessels of different sizes leads to a variable susceptibility to local coagulopathythrough hyperfibrinolysis. This can explain many of the clinical observations inthe early stages from severely injured coagulopathic patients. In addition, we simulatethe efficacy of tranexamic acid treatment on coagulopathy initiated through endothelialt-PA release, and are able to reproduce the time-sensitive nature of the efficacy of thistreatment as observed in clinical studies. We also provide a model which can simulateempirical studies on current and future treatments to improve our understanding and tohelp develop new treatments