Stochastic Modeling of Blood Coagulation Initiation

  • Lo K
  • Denney W
  • Diamon S
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Abstract

A kinetic Monte Carlo simulation was developed using\r
the deterministic reaction network developed by the\r
Mann laboratory for tissue-factor (TF)-initiated blood coagulation.\r
The model predicted thrombin dynamics in\r
recalcifi ed whole blood (3-fold diluted) pretreated with\r
convulxin (platelet GPVI activator) and picomolar levels\r
of TF (0–14 pM ). The model did not accurately predict\r
coagulation times at low TF (0–0.7 pM ). The simulation\r
revealed that  0.2 pM TF was the critical concentration\r
to cause 50% of reactions containing 3-fold diluted whole\r
blood to reach a clotting threshold of 0.05 U/ml thrombin\r
by 1 h. Simulations of 1 nl of blood (5 pM TF) revealed\r
small stochastic variations in thrombin initiation time,\r
while 16.6 pl simulations were highly stochastic at this\r
level of TF (50 molecules/16.6 pl). Further experiment\r
and simulation will require evaluation of mechanisms of\r
coagulation kinetics at subpicomolar levels of TF.

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Authors

  • Ken Lo

  • William Denney

  • Scott Diamon

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