public model
Model Identifier
BIOMD0000000335
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 , PubMed ID: 11893748
  • 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
Submitter of the first revision: Michael Schubert
Submitter of this revision: Michael Schubert
Modellers: Michael Schubert

Metadata information

is (2 statements)
BioModels Database MODEL1106010000
BioModels Database BIOMD0000000335

isDerivedFrom (1 statement)
BioModels Database BIOMD0000000336

isDescribedBy (1 statement)
PubMed 11893748

hasTaxon (1 statement)
Taxonomy Homo sapiens

isVersionOf (1 statement)
Gene Ontology blood coagulation

occursIn (1 statement)
Brenda Tissue Ontology blood plasma


Curation status
Curated

Connected external resources

Name Description Size Actions

Model files

BIOMD0000000335_url.xml SBML L2V4 representation of Hockin2002_BloodCoagulation 61.74 KB Preview | Download

Additional files

BIOMD0000000335-biopax2.owl Auto-generated BioPAX (Level 2) 55.29 KB Preview | Download
BIOMD0000000335-biopax3.owl Auto-generated BioPAX (Level 3) 95.59 KB Preview | Download
BIOMD0000000335.m Auto-generated Octave file 14.59 KB Preview | Download
BIOMD0000000335.pdf Auto-generated PDF file 302.20 KB Preview | Download
BIOMD0000000335.png Auto-generated Reaction graph (PNG) 398.69 KB Preview | Download
BIOMD0000000335.sci Auto-generated Scilab file 12.86 KB Preview | Download
BIOMD0000000335.svg Auto-generated Reaction graph (SVG) 88.69 KB Preview | Download
BIOMD0000000335.vcml Auto-generated VCML file 88.83 KB Preview | Download
BIOMD0000000335.xpp Auto-generated XPP file 10.66 KB Preview | Download
BIOMD0000000335_urn.xml Auto-generated SBML file with URNs 60.54 KB Preview | Download

  • Model originally submitted by : Michael Schubert
  • Submitted: Jun 1, 2011 3:29:34 PM
  • Last Modified: May 28, 2014 2:55:22 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: May 28, 2014 2:55:22 PM
    • Submitted by: Michael Schubert
    • With comment: Current version of Hockin2002_BloodCoagulation
  • Version: 1 public model Download this version
    • Submitted on: Jun 1, 2011 3:29:34 PM
    • Submitted by: Michael Schubert
    • With comment: Original import of Hockin 2002

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
Reactions
Reactions Rate Parameters
TF + VII => TF_VII compartment_1*(k2*TF*VII-k1*TF_VII) k2 = 3200000.0; k1 = 0.0031
Xa + VII => Xa + VIIa compartment_1*k6*Xa*VII k6 = 1.3E7
IIa + VII => IIa + VIIa compartment_1*k7*IIa*VII k7 = 23000.0
IXa + ATIII => IXa_ATIII compartment_1*k40*IXa*ATIII k40 = 490.0
TF_VIIa + Xa_TFPI => TF_VIIa_Xa_TFPI compartment_1*k37*TF_VIIa*Xa_TFPI k37 = 5.0E7
IIa + ATIII => IIa_ATIII compartment_1*k41*IIa*ATIII k41 = 7100.0
IXa_VIIIa_X => IXa_VIIIa + Xa compartment_1*k22*IXa_VIIIa_X k22 = 8.2
TF_VIIa + ATIII => TF_VIIa_ATIII compartment_1*k42*TF_VIIa*ATIII k42 = 230.0
TF_VIIa + X => TF_VIIa_X compartment_1*(k9*TF_VIIa*X-k8*TF_VIIa_X) k9 = 2.5E7; k8 = 1.05
Xa + Va => Xa_Va compartment_1*(k28*Xa*Va-k27*Xa_Va) k27 = 0.2; k28 = 4.0E8
TF_VIIa_Xa + TFPI => TF_VIIa_Xa_TFPI compartment_1*(k36*TF_VIIa_Xa*TFPI-k35*TF_VIIa_Xa_TFPI) k35 = 1.1E-4; k36 = 3.2E8
TF_VIIa + IX => TF_VIIa_IX compartment_1*(k14*TF_VIIa*IX-k13*TF_VIIa_IX) k14 = 1.0E7; k13 = 2.4
IXa_VIIIa + X => IXa_VIIIa_X compartment_1*(k21*IXa_VIIIa*X-k20*IXa_VIIIa_X) k21 = 1.0E8; k20 = 0.001
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.