Adams2003 - Thrombin Inhibitors

  public model
Model Identifier
MODEL1808150002
Short description
Mathematical model of blood coagulation. Reused Hockin et al. 2002 model. Simulation of thrombin inhibitors: Hirudin, Hirulog, Argatroban, Melagatran and Efegatran.
Format
SBML (L2V4)
Related Publication
  • Predicting the pharmacology of thrombin inhibitors.
  • Adams TE, Everse SJ, Mann KG
  • Journal of thrombosis and haemostasis : JTH , 5/ 2003 , Volume 1 , Issue 5 , pages: 1024-1027 , PubMed ID: 12871372
  • Department of Biochemistry, University of Vermont, College of Medicine, Burlington, Vermont 05405, USA. tadams@zoo.uvm.edu
  • Thrombotic disorders can lead to uncontrolled thrombin generation and clot formation within the circulatory system leading to vascular thrombosis. Direct inhibitors of thrombin have been developed and tested in clinical trials for the treatment of a variety of these thrombotic disorders. The bleeding complications observed during these trials have raised questions about their clinical use. The development of a computer-based model of coagulation using the kinetic rates of individual reactions and concentrations of the constituents involved in each reaction within blood has made it possible to study coagulation pathologies in silico. We present an extension of our initial model of coagulation to include several specific thrombin inhibitors. Using this model we have studied the effect of a variety of inhibitors on thrombin generation and compared these results with the clinically observed data. The data suggest that numerical models will be useful in predicting the effectiveness of inhibitors of coagulation.
Contributors
Submitter of the first revision: Matthew Roberts
Submitter of this revision: Matthew Roberts
Modellers: Matthew Roberts

Metadata information

isDescribedBy (1 statement)
PubMed 12871372

isVersionOf (1 statement)
Gene Ontology blood coagulation


Curation status
Non-curated

Tags

Connected external resources

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Model files

Adams2003.xml SBML L2V4 representation of Adams2003 - Thrombin Inhibitors 170.30 KB Preview | Download

Additional files

Adams2003.cps Model COPASI file. Reused Hockin2002 model. 10 new reactions added for the interactions between the 5 inhibitors and IIa and mIIa. TF reduced from 2.5e-11 M to 1.0e-11 M. 212.59 KB Preview | Download
fig1.png Attempt at reproducing figure 1. Thrombin peaks occur too early. 16.33 KB Preview | Download
fig4.png Attempt at reproducing figure 4, varying the initial concentration of Hirulog. Clot time occurs too soon. 17.27 KB Preview | Download

  • Model originally submitted by : Matthew Roberts
  • Submitted: Aug 15, 2018 5:25:00 PM
  • Last Modified: Aug 15, 2018 5:25:00 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: Aug 15, 2018 5:25:00 PM
    • Submitted by: Matthew Roberts
    • With comment: Edited model metadata online.