Pathophysiology of Haemostasis and Thrombosis
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Stochastic Modeling of Blood Coagulation InitiationLo K. · Denney W.S. · Diamond S.L.Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, University of Pennsylvania, 1024 Vagelos Research Laboratories, Philadelphia, Pa., USA
Scott L. Diamond Institute for Medicine and Engineering Department of Chemical and Biomolecular Engineering, University of Pennsylvania 1024 Vagelos Research Laboratories, Philadelphia, PA 19104 (USA) Tel. +1 215 573 5702, Fax +1 215 573 7227, E-Mail sld@seas.upenn.edu |
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Pathophysiol Haemos Thromb 2005;34:80–90
Abstract
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 ∼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.
© 2005 S. Karger AG, Basel
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Article / Publication Details
First-Page Preview
Published online: January 26, 2006
Issue release date: January 2006
Number of Print Pages: 11
Number of Figures: 5
Number of Tables: 3
ISSN: 1424-8832 (Print)
eISSN: 1424-8840 (Online)
For additional information: https://www.karger.com/PHT
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