Dataset Information

Orfeo2010 - Simulating the effects of fondaparinux and Rivaroxaban on thrombin generation

ABSTRACT: Reused mathematical model (Hockin et al., 2002) of blood coagulation simulating the effects of coagulation factor inhibitors, fondaparinux (synthetic heparin) and Rivaroxaban. Fondaparinux (Fpx) simulated to reversibly bind with ATIII before irreversibly binding to Xa, IXa, mIIa, TF:VIIa, Xa:Va and IIa. Rivaroxaban simulated to bind reversibly to Xa and Xa:Va.

SUBMITTER: Matthew Roberts

PROVIDER: MODEL1807240001 | BioModels | 2018-07-24

REPOSITORIES: BioModels

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	MODEL1807240001?filename=Orfeo2010.cps	Other
	MODEL1807240001?filename=Orfeo2010.xml	Xml
	MODEL1807240001?filename=fig.jpg	Other

Items per page:

1 - 3 of 3

Publications

Anticoagulation by factor Xa inhibitors.

Orfeo T T Butenas S S Brummel-Ziedins K E KE Gissel M M Mann K G KG

Journal of thrombosis and haemostasis : JTH 20100521 8

<h4>Background</h4>Therapeutic agents that regulate blood coagulation are critical to the management of thrombotic disorders, with the selective targeting of factor (F) Xa emerging as a promising approach.<h4>Objective</h4>To assess anticoagulant strategies targeting FXa.<h4>Methods</h4>A deterministic computational model of tissue factor (Tf)-initiated thrombin generation and two empirical experimental systems (a synthetic coagulation proteome reconstruction using purified proteins and a whole ...[more]

PMID: 20492473

Similar Datasets

Project 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.