Burghaus2014 - Simulating blood coagulation factor Xa inhibitors

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Model Identifier
Short description
Mathematical model of blood coagulation factors II, VII, IX and X as well as protein C and protein S and the effect of warfarin on kinetic rates.
Related Publication
  • Computational investigation of potential dosing schedules for a switch of medication from warfarin to rivaroxaban-an oral, direct Factor Xa inhibitor.
  • Burghaus R, Coboeken K, Gaub T, Niederalt C, Sensse A, Siegmund HU, Weiss W, Mueck W, Tanigawa T, Lippert J
  • Frontiers in physiology , 1/ 2014 , Volume 5 , pages: 417 , PubMed ID: 25426077
  • Bayer HealthCare Wuppertal, Germany.
  • The long-lasting anticoagulant effect of vitamin K antagonists can be problematic in cases of adverse drug reactions or when patients are switched to another anticoagulant therapy. The objective of this study was to examine in silico the anticoagulant effect of rivaroxaban, an oral, direct Factor Xa inhibitor, combined with the residual effect of discontinued warfarin. Our simulations were based on the recommended anticoagulant dosing regimen for stroke prevention in patients with atrial fibrillation. The effects of the combination of discontinued warfarin plus rivaroxaban were simulated using an extended version of a previously validated blood coagulation computer model. A strong synergistic effect of the two distinct mechanisms of action was observed in the first 2-3 days after warfarin discontinuation; thereafter, the effect was close to additive. Nomograms for the introduction of rivaroxaban therapy after warfarin discontinuation were derived for Caucasian and Japanese patients using safety and efficacy criteria described previously, together with the coagulation model. The findings of our study provide a mechanistic pharmacologic rationale for dosing schedules during the therapy switch from warfarin to rivaroxaban and support the switching strategies as outlined in the Summary of Product Characteristics and Prescribing Information for rivaroxaban.
Submitter of the first revision: Matthew Roberts
Submitter of this revision: Matthew Roberts
Modellers: Matthew Roberts

Metadata information

isDescribedBy (1 statement)
PubMed 25426077

isVersionOf (1 statement)
Gene Ontology blood coagulation

hasPart (2 statements)
KEGG Drug Rivaroxaban (JAN/USAN/INN)
KEGG Compound Warfarin

Curation status


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Model files

Burghaus2014.xml SBML L2V4 representation of Burghaus2014 - Simulating blood coagulation factor Xa inhibitors 37.70 KB Preview | Download

Additional files

Burghaus2014.cps Model COPASI file. Attempt at reproducing figure 2. Simulated behaviour for 'Onset of Therapy' and 'Discontinuation of therapy' was completely opposite to what is presented in the publication. Species' levels rose when warfarin concentration was non-zero and levels decreased when warfarin levels were set to zero. 83.21 KB Preview | Download
fig2_1.png Simulation behaviour once Warfarin concentration was set to zero. 23.04 KB Preview | Download
fig2_2.png Simulation behaviour with non-zero Warfarin concentration. 20.07 KB Preview | Download

  • Model originally submitted by : Matthew Roberts
  • Submitted: Jul 18, 2018 3:29:08 PM
  • Last Modified: Jul 18, 2018 3:29:08 PM
  • Version: 2 public model Download this version
    • Submitted on: Jul 18, 2018 3:29:08 PM
    • Submitted by: Matthew Roberts
    • With comment: Edited model metadata online.