Hockin2002_BloodCoagulation

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Short description

This model is from the article:
A model for the stoichiometric regulation of blood coagulation.
Hockin MF, Jones KC, Everse SJ, Mann KG. Journal of Biological ChemistryVolume 277, Issue 21, 24 May 2002, Pages 18322 -18333 11893748,
Abstract:
We have developed a model of the extrinsic blood coagulation system that includes the stoichiometric anticoagulants. The model accounts for the formation, expression, and propagation of the vitamin K-dependent procoagulant complexes and extends our previous model by including: (a) the tissue factor pathway inhibitor (TFPI)-mediated inactivation of tissue factor (TF).VIIa and its product complexes; (b) the antithrombin-III (AT-III)-mediated inactivation of IIa, mIIa, factor VIIa, factor IXa, and factor Xa; (c) the initial activation of factor V and factor VIII by thrombin generated by factor Xa-membrane; (d) factor VIIIa dissociation/activity loss; (e) the binding competition and kinetic activation steps that exist between TF and factors VII and VIIa; and (f) the activation of factor VII by IIa, factor Xa, and factor IXa. These additions to our earlier model generate a model consisting of 34 differential equations with 42 rate constants that together describe the 27 independent equilibrium expressions, which describe the fates of 34 species. Simulations are initiated by "exposing" picomolar concentrations of TF to an electronic milieu consisting of factors II, IX, X, VII, VIIa, V, and VIIII, and the anticoagulants TFPI and AT-III at concentrations found in normal plasma or associated with coagulation pathology. The reaction followed in terms of thrombin generation, proceeds through phases that can be operationally defined as initiation, propagation, and termination. The generation of thrombin displays a nonlinear dependence upon TF, AT-III, and TFPI and the combination of these latter inhibitors displays kinetic thresholds. At subthreshold TF, thrombin production/expression is suppressed by the combination of TFPI and AT-III; for concentrations above the TF threshold, the bolus of thrombin produced is quantitatively equivalent. A comparison of the model with empirical laboratory data illustrates that most experimentally observable parameters are captured, and the pathology that results in enhanced or deficient thrombin generation is accurately described.

Format
SBML (L2V4)
Related Publication
  • A model for the stoichiometric regulation of blood coagulation.
  • Hockin MF, Jones KC, Everse SJ, Mann KG
  • The Journal of biological chemistry , 5/ 2002 , Volume 277 , pages: 18322-18333
  • Department of Biochemistry, College of Medicine, University of Vermont, Burlington, Vermont 05405, USA.
  • We have developed a model of the extrinsic blood coagulation system that includes the stoichiometric anticoagulants. The model accounts for the formation, expression, and propagation of the vitamin K-dependent procoagulant complexes and extends our previous model by including: (a) the tissue factor pathway inhibitor (TFPI)-mediated inactivation of tissue factor (TF).VIIa and its product complexes; (b) the antithrombin-III (AT-III)-mediated inactivation of IIa, mIIa, factor VIIa, factor IXa, and factor Xa; (c) the initial activation of factor V and factor VIII by thrombin generated by factor Xa-membrane; (d) factor VIIIa dissociation/activity loss; (e) the binding competition and kinetic activation steps that exist between TF and factors VII and VIIa; and (f) the activation of factor VII by IIa, factor Xa, and factor IXa. These additions to our earlier model generate a model consisting of 34 differential equations with 42 rate constants that together describe the 27 independent equilibrium expressions, which describe the fates of 34 species. Simulations are initiated by "exposing" picomolar concentrations of TF to an electronic milieu consisting of factors II, IX, X, VII, VIIa, V, and VIIII, and the anticoagulants TFPI and AT-III at concentrations found in normal plasma or associated with coagulation pathology. The reaction followed in terms of thrombin generation, proceeds through phases that can be operationally defined as initiation, propagation, and termination. The generation of thrombin displays a nonlinear dependence upon TF, AT-III, and TFPI and the combination of these latter inhibitors displays kinetic thresholds. At subthreshold TF, thrombin production/expression is suppressed by the combination of TFPI and AT-III; for concentrations above the TF threshold, the bolus of thrombin produced is quantitatively equivalent. A comparison of the model with empirical laboratory data illustrates that most experimentally observable parameters are captured, and the pathology that results in enhanced or deficient thrombin generation is accurately described.
Contributors
Michael Schubert

Metadata information

is
BioModels Database MODEL1106010000
BioModels Database BIOMD0000000335
isDerivedFrom
BioModels Database BIOMD0000000336
isDescribedBy
PubMed 11893748
hasTaxon
Taxonomy Homo sapiens
isVersionOf
Gene Ontology blood coagulation
occursIn
Brenda Tissue Ontology blood plasma
Curation status
Curated
Name Description Size Actions

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  • Model originally submitted by : Michael Schubert
  • Submitted: 01-Jun-2011 15:29:34
  • Last Modified: 28-May-2014 14:55:22
Revisions
  • Version: 2 public model Download this version
    • Submitted on: 28-May-2014 14:55:22
    • Submitted by: Michael Schubert
    • With comment: Current version of Hockin2002_BloodCoagulation
  • Version: 1 public model Download this version
    • Submitted on: 01-Jun-2011 15:29:34
    • Submitted by: Michael Schubert
    • With comment: Original import of Hockin 2002
Curator's comment:
(added: 01 Jun 2011, 15:34:56, updated: 01 Jun 2011, 15:34:56)
Thrombin generation model by Hockin et al, 2002. Factors are denoted by their roman numberals. Initial concentration of Tissue Factor (TF) was varied from 25pM (in model file) to values seen in the plot. Simulation using Copasi (LSODE) and rendering using Matplotlib.