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Related Publication
  • Tolerance and threshold in the extrinsic coagulation system.
  • Müller J, Brandt S, Mayerhofer K, Tjardes T, Maegele M
  • Mathematical biosciences , 2/ 2008 , Volume 211 , pages: 226-254
  • Technical University Munich, Centre for Mathematical Sciences, Boltzmannstr. 3, D-85748 Garching/Munich, Germany.
  • This paper focus on the quest for mechanisms that are able to create tolerance and an activation threshold in the extrinsic coagulation cascade. We propose that the interplay of coagulation inhibitor and blood flow creates threshold behavior. First we test this hypothesis in a minimal, four dimensional model. This model can be analysed by means of time scale analysis. We find indeed that only the interplay of blood flow and inhibition together are able to produce threshold behavior. The mechanism relays on a combination of raw substance supply and wash-out effect by the blood flow and a stabilization of the resting state by the inhibition. We use the insight into this minimal model to interpret the simulation results of a large model. Here, we find that the initiating steps (TF that produces together with fVII(a) factor Xa) does not exhibit threshold behavior, but the overall system does. Hence, the threshold behavior appears via the feedback loop (in that fIIa produces indirectly fXa that in turn produces fIIa again) inhibited by ATIII and blood flow.
Michael Schubert

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Curation status
  • Model originally submitted by : Michael Schubert
  • Submitted: Aug 26, 2011 5:51:38 PM
  • Last Modified: Oct 9, 2014 6:24:16 PM
  • Version: 2 public model Download this version
    • Submitted on: Oct 9, 2014 6:24:16 PM
    • Submitted by: Michael Schubert
    • With comment: Current version of Muller2008_treshold_minimal
  • Version: 1 public model Download this version
    • Submitted on: Aug 26, 2011 5:51:38 PM
    • Submitted by: Michael Schubert
    • With comment: Original import of Mueller_ThrombinGeneration_minimal
Curator's comment:
(added: 15 Sep 2011, 12:35:42, updated: 15 Sep 2011, 12:35:42)
Reproduction of figure 5 of the article in one plot: Time course of the complete minimal model with flow and activation of anti-coagulatory substances. Integrated with Copasi, plotted with Matplotlib.