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