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hockin1

hockin1

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R1

R1

TF + VII = TF_VII

R10

R10

IIa + VIII > IIa + VIIIa

R11

R11

IXa + VIIIa = IXa_VIIIa

R12

R12

IXa_VIIIa + X = IXa_VIIIa_X

R12b

R12b

IXa_VIIIa_X > IXa_VIIIa + Xa

R13

R13

VIIIa = VIIIa1_L + VIIIa2

R14

R14

IXa_VIIIa_X > VIIIa1_L + VIIIa2 + X + IXa

R15

R15

IXa_VIIIa > VIIIa1_L + VIIIa2 + IXa

R16

R16

IIa + V > IIa + Va

R17

R17

Xa + Va = Xa_Va

R18

R18

Xa_Va + II = Xa_Va_II

R18b

R18b

Xa_Va_II > Xa_Va + mIIa

R19

R19

mIIa + Xa_Va > IIa + Xa_Va

R2

R2

TF + VIIa = TF_VIIa

R20

R20

Xa + TFPI = Xa_TFPI

R21

R21

TF_VIIa_Xa + TFPI = TF_VIIa_Xa_TFPI

R22

R22

TF_VIIa + Xa_TFPI > TF_VIIa_Xa_TFPI

R23

R23

Xa + ATIII > Xa_ATIII

R24

R24

mIIa + ATIII > mIIa_ATIII

R25

R25

IXa + ATIII > IXa_ATIII

R26

R26

IIa + ATIII > IIa_ATIII

R27

R27

TF_VIIa + ATIII > TF_VIIa_ATIII

R3

R3

TF_VIIa + VII > TF_VIIa + VIIa

R4

R4

Xa + VII > Xa + VIIa

R5

R5

VII + IIa > IIa + VIIa

R6

R6

TF_VIIa + X = TF_VIIa_X

R6b

R6b

TF_VIIa_X > TF_VIIa_Xa

R7

R7

TF_VIIa + Xa = TF_VIIa_Xa

R8

R8

TF_VIIa + IX = TF_VIIa_IX

R8b

R8b

TF_VIIa_IX > TF_VIIa + IXa

R9

R9

Xa + II > Xa + IIa

Parameters

Global parameters

Fixed species

Initial values

Functions and Rules

Assignment rules

IIa_plus_1_2mIIa = IIa + 1.2 * mIIa

Function definitions

Events

Constraints

Note that constraints are not enforced in simulations. It remains the responsibility of the user to verify that simulation results satisfy these constraints.


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A model for the stoichiometric regulation of blood coagulation.

  • Matthew F Hockin
  • Kenneth C Jones
  • Stephen J Everse
  • Kenneth G Mann
J. Biol. Chem. 2002; 277 (21): 18322-18333
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.
The SBML for this model was obtained from the BioModels database (BioModels ID: BIOMD0000000335) Biomodels notes: 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. JWS Online curation: This model was curated by reproducing the figures as described in the BioModels Notes. No additional changes were made.