Hartmann2016 - Blood coagulation model for simulating anticoagulants
ABSTRACT: Mathematical model of blood coagulation. Reused Wajima2009 model with modifications to reactions 27 (formation of Va:Xa complex), 32 (Xa inhibition by TFPI) and 45 (Xa inhibition by TFPI-Heparin complex) as described in publication equations 2,3 and 4. Publication lists parameter sets to simulate Rivaroxaban, VKA and Enoxaparin (supplementary files).
CPT: pharmacometrics & systems pharmacology 20160920 10
Warfarin is the anticoagulant of choice for venous thromboembolism (VTE) treatment, although its suppression of the endogenous clot-dissolution complex APC:PS may ultimately lead to longer time-to-clot dissolution profiles, resulting in increased risk of re-thrombosis. This detrimental effect might not occur during VTE treatment using other anticoagulants, such as rivaroxaban or enoxaparin, given their different mechanisms of action within the coagulation network. A quantitative systems pharmaco ...[more]
Project description:Blood coagulation model investigating effects of Xa-inhibitors (Rivaroxaban and Apixaban). Model is an extension of Pohl1994 and reduced from Wajima2009.
Encoding the model from the supplementary files results in 43 species, 82 reactions and 111 parameters. Including the drug (Xa-inhibitor) and drug-Xa complexes results in 46 species, 84 reactions and 115 parameters (+1 dummy variable to change inhibitory kinetic parameters depending on which drug is simulated). The publication lists there being 45 species, 84 reactions and 116 parameters. Publication figure 2 has 45 species present however the complex VIIa:Xa (reaction 51 involving Xa and VIIa) is not shown. This figure also has numerous small errors such as listing IXa:ATIII complex twice (instead of one being XIa:ATIII), not showing XIa:ATIII, typo ('Va' -> Va), typo (IXa + VIIIa -> IXA:'VIIa').
Rate laws for Xa-drug interactions were assumed to be mass action.
Project description:Mathematical model of blood coagulation to simulate factor IIa, Va and Xa concentration profiles. Publication also illustrates the effect of hirudin on factor IIa, Va and Xa generation.
Project description:System of ODEs to describe the behaviour of the activated factors of the extrinsic pathway of blood coagulation with the addition of the TFPI-Xa complex. Mass-action kinetics used with the only exception of factor IIa production (Michaelis-Menten rate law).
Project description: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.
Project description:Blood coagulation mathematical model derived from Chatterjee et al. (2010) and Hockin et al. (2002). Included various inhibitors: TFPI, ATIII, generic kallikrein inhibitor, C1-inhibitor, alpha1-antitrypsin and alpha2-antiplasmin.