Stochastic modeling of blood coagulation initiation.
A kinetic Monte Carlo simulation was developed using the deterministic reaction network developed by the Mann laboratory for tissue-factor (TF)-initiated blood coagulation. The model predicted thrombin dynamics in recalcified whole blood (3-fold diluted) pretreated with convulxin (platelet GPVI activator) and picomolar levels of TF (0-14 pM). The model did not accurately predict coagulation times at low TF (0-0.7 pM). The simulation revealed that approximately 0.2 pM TF was the critical concentration to cause 50% of reactions containing 3-fold diluted whole blood to reach a clotting threshold of 0.05 U/ml thrombin by 1 h. Simulations of 1 nl of blood (5 pM TF) revealed small stochastic variations in thrombin initiation time, while 16.6 pl simulations were highly stochastic at this level of TF (50 molecules/16.6 pl). Further experiment and simulation will require evaluation of mechanisms of coagulation kinetics at subpicomolar levels of TF.
Lo
Ken
K
Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, 19104, USA.
Denney
William S
WS
Diamond
Scott L
SL
D001331:Automation; D001777:Blood Coagulation; D001780:Blood Coagulation Tests / Q000295:instrumentation*; D003198:Computer Simulation; D009010:Monte Carlo Method; D013925:Thromboplastin / Q000737:chemistry*; D017186:Titrimetry / Q000379:methods
D013925:Thromboplastin