Mitrophanov2011 - Mode of action of rFVIIa on thrombin generation (Update to Hockin2002 Blood Coagulation Model)

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Model Identifier
MODEL1806040001
Short description
Mathematical model of blood coagulation investigating effects of varied factor VIIa on thrombin generation. Model derived from Hockin2002/Butenas2004. Butenas added two new reactions (R28 and R29) and two new parameters (k43 and k44). Here, changes to parameters k32 and k38 and TF initial conc. changed to 5e-12
Format
SBML (L2V4)
Related Publication
  • Kinetic modeling sheds light on the mode of action of recombinant factor VIIa on thrombin generation.
  • Mitrophanov AY, Reifman J
  • Thrombosis research , 10/ 2011 , Volume 128 , Issue 4 , pages: 381-390 , PubMed ID: 21641634
  • DoD Biotechnology High-Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, US Army Medical Research and Materiel Command, ATTN: MCMR-TT, 504 Scott Street, Ft Detrick, MD 21702, USA. alex@bioanalysis.org
  • INTRODUCTION: The therapeutic potential of a hemostatic agent can be assessed by investigating its effects on the quantitative parameters of thrombin generation. For recombinant activated factor VII (rFVIIa)--a promising hemostasis-inducing biologic--experimental studies addressing its effects on thrombin generation yielded disparate results. To elucidate the inherent ability of rFVIIa to modulate thrombin production, it is necessary to identify rFVIIa-induced effects that are compatible with the available biochemical knowledge about thrombin generation mechanisms. MATERIALS AND METHODS: The existing body of knowledge about coagulation biochemistry can be rigorously represented by a computational model that incorporates the known reactions and parameter values constituting the biochemical network. We used a thoroughly validated numerical model to generate activated factor VII (FVIIa) titration curves in the cases of normal blood composition, hemophilia A and B blood, blood lacking factor VII, blood lacking tissue factor pathway inhibitor, and diluted blood. We utilized the generated curves to perform systematic fold-change analyses for five quantitative parameters characterizing thrombin accumulation. RESULTS: The largest fold changes induced by increasing FVIIa concentration were observed for clotting time, thrombin peak time, and maximum slope of the thrombin curve. By contrast, thrombin peak height was much less affected by FVIIa titrations, and the area under the thrombin curve stayed practically unchanged. Comparisons with experimental data demonstrated that the computationally derived patterns can be observed in vitro. CONCLUSIONS: rFVIIa modulates thrombin generation primarily by accelerating the process, without significantly affecting the total amount of generated thrombin.
Contributors
Submitter of the first revision: Matthew Roberts
Submitter of this revision: Matthew Roberts
Modellers: Matthew Roberts

Metadata information

isDescribedBy (1 statement)
PubMed 21641634

hasTaxon (1 statement)
Taxonomy Homo sapiens

isVersionOf (2 statements)
Gene Ontology blood coagulation
BioModels Database BIOMD0000000362

occursIn (1 statement)
Brenda Tissue Ontology blood plasma

Curation status
Non-curated
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Model files
Mitrophanov2011_edited.xml SBML L2V4 representation of Mitrophanov2011 - Mode of action of rFVIIa on thrombin generation (Update to Hockin2002 Blood Coagulation Model) 148.47 KB Preview | Download

Additional files
Mitrophanov2011.cps Curated and annotated model COPASI file. 188.02 KB Preview | Download
Mitrophanov2011_edited.cps Curated model COPASI file. 187.80 KB Preview | Download
fig.jpg Figure 1 A reproduced. Simulations performed in COPASI 4.22 (Build 170). Figure generated in MATLAB R2014b. VIIa varied from 1e-10 to 4e-8 M. 27.68 KB Preview | Download

  • Model originally submitted by : Matthew Roberts
  • Submitted: Jun 4, 2018 3:20:51 PM
  • Last Modified: Jun 5, 2018 3:23:32 PM
Revisions
  • Version: 8 public model Download this version
    • Submitted on: Jun 5, 2018 3:23:32 PM
    • Submitted by: Matthew Roberts
    • With comment: Edited model metadata online.
  • Version: 6 public model Download this version
    • Submitted on: Jun 4, 2018 3:27:27 PM
    • Submitted by: Matthew Roberts
    • With comment: Edited model metadata online.
  • Version: 2 public model Download this version
    • Submitted on: Jun 4, 2018 3:20:51 PM
    • Submitted by: Matthew Roberts
    • With comment: Edited model metadata online.

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