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Computational Analysis of Acute Traumatic Coagulopathy

  • Author(s): Wu, Tie Bo
  • Advisor(s): Petzold, Linda R
  • et al.
Abstract

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.

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