Stochastic Modeling of Blood Coagulation Initiation

@article{citeulike:2683083, 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.}, author = {Lo, Ken and Denney, William S. and Diamond, Scott L. }, citeulike-article-id = {2683083}, journal = {Pathophysiology of Haemostasis and Thrombosis}, keywords = {coagulation, fluorescence, kinetics, thrombin}, number = {2-3}, pages = {80--90}, posted-at = {2008-04-17 19:01:53}, priority = {2}, title = {Stochastic Modeling of Blood Coagulation Initiation}, url = {http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract\&\#38;ArtikelNr=89929\&\#38;Ausgabe=231541\&\#38;ProduktNr=224034}, volume = {34}, year = {2005} }

TY - JOUR ID - citeulike:2683083 L3 - citeulike-article-id:2683083 TI - Stochastic Modeling of Blood Coagulation Initiation JF - Pathophysiology of Haemostasis and Thrombosis VL - 34 IS - 2-3 SP - 80 EP - 90 N2 - 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. KW - coagulation KW - fluorescence KW - kinetics KW - thrombin AU - Lo, Ken AU - Denney, William AU - Diamond, Scott PY - 2005/// UR - http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ArtikelNr=89929&Ausgabe=231541&ProduktNr=224034 ER -