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- Surface-mediated control of blood coagulation: the role of binding site densities and platelet deposition.
- Kuharsky AL, Fogelson AL
- Biophysical Journal , 3/ 2001 , Volume 80 , pages: 1050-1074 , PubMed ID: 11222273
- Generation5, Toronto, Ontario, Canada.
- A mathematical model of the extrinsic or tissue factor (TF) pathway of blood coagulation is formulated and results from a computational study of its behavior are presented. The model takes into account plasma-phase and surface-bound enzymes and zymogens, coagulation inhibitors, and activated and unactivated platelets. It includes both plasma-phase and membrane-phase reactions, and accounts for chemical and cellular transport by flow and diffusion, albeit in a simplified manner by assuming the existence of a thin, well-mixed fluid layer, near the surface, whose thickness depends on flow. There are three main conclusions from these studies. (i) The model system responds in a threshold manner to changes in the availability of particular surface binding sites; an increase in TF binding sites, as would occur with vascular injury, changes the system's production of thrombin dramatically. (ii) The model suggests that platelets adhering to and covering the subendothelium, rather than chemical inhibitors, may play the dominant role in blocking the activity of the TF:VIIa enzyme complex. This, in turn, suggests that a role of the IXa-tenase pathway for activating factor X to Xa is to continue factor Xa production after platelets have covered the TF:VIIa complexes on the subendothelium. (iii) The model gives a kinetic explanation of the reduced thrombin production in hemophilias A and B.
Submitter of this revision: Michael Schubert
Modellers: Michael Schubert
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- Model originally submitted by : Michael Schubert
- Submitted: Sep 15, 2011 2:19:47 PM
- Last Modified: Sep 15, 2011 2:31:35 PM
- Submitted on: Sep 15, 2011 2:31:35 PM
- Submitted by: Michael Schubert
- With comment: Current version of Kuharsky2001_BloodCoagulation
- Submitted on: Sep 15, 2011 2:19:47 PM
- Submitted by: Michael Schubert
- With comment: Original import of Kuharsky2001_BloodCoagulation
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