Mitrophanov2014 - Extended Hockin Blood Coagulation Model with additional fibrin-associated species

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Short description
Mathematical model of the blood coagulation cascade. Extended Hockin model with contributions from Kim2007, Naski1991, Schneider2004, Horrevoets1996, Brummel-Ziedins2012, Mitrophanov2012, Danforth2009 and Hekman1988. Model incorporates more fibrin associated species such as fibrin I and II monomers and fibrinopeptide A and B as well as factor V fragments.
Related Publication
  • Kinetic model facilitates analysis of fibrin generation and its modulation by clotting factors: implications for hemostasis-enhancing therapies.
  • Mitrophanov AY, Wolberg AS, Reifman J
  • Molecular bioSystems , 7/ 2014 , Volume 10 , Issue 9 , pages: 2347-2357 , PubMed ID: 24958246
  • DoD Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research Center, U.S. Army Medical Research and Materiel Command, ATTN: MCMR-TT, 504 Scott Street, Ft. Detrick, MD 21702, USA.
  • Current mechanistic knowledge of protein interactions driving blood coagulation has come largely from experiments with simple synthetic systems, which only partially represent the molecular composition of human blood plasma. Here, we investigate the ability of the suggested molecular mechanisms to account for fibrin generation and degradation kinetics in diverse, physiologically relevant in vitro systems. We represented the protein interaction network responsible for thrombin generation, fibrin formation, and fibrinolysis as a computational kinetic model and benchmarked it against published and newly generated data reflecting diverse experimental conditions. We then applied the model to investigate the ability of fibrinogen and a recently proposed prothrombin complex concentrate composition, PCC-AT (a combination of the clotting factors II, IX, X, and antithrombin), to restore normal thrombin and fibrin generation in diluted plasma. The kinetic model captured essential features of empirically detected effects of prothrombin, fibrinogen, and thrombin-activatable fibrinolysis inhibitor titrations on fibrin formation and degradation kinetics. Moreover, the model qualitatively predicted the impact of tissue factor and tPA/tenecteplase level variations on the fibrin output. In the majority of considered cases, PCC-AT combined with fibrinogen accurately approximated both normal thrombin and fibrin generation in diluted plasma, which could not be accomplished by fibrinogen or PCC-AT acting alone. We conclude that a common network of protein interactions can account for key kinetic features characterizing fibrin accumulation and degradation in human blood plasma under diverse experimental conditions. Combined PCC-AT/fibrinogen supplementation is a promising strategy to reverse the deleterious effects of dilution-induced coagulopathy associated with traumatic bleeding.
Submitter of the first revision: Matthew Roberts
Submitter of this revision: Matthew Roberts
Modellers: Matthew Roberts

Metadata information

hasPart (1 statement)
BioModels Database BIOMD0000000335

isDescribedBy (1 statement)
PubMed 24958246

hasTaxon (1 statement)
Taxonomy Homo sapiens

isVersionOf (1 statement)
Gene Ontology blood coagulation

occursIn (1 statement)
Brenda Tissue Ontology blood plasma

Curation status


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Model files

Mitrophanov2014.xml SBML L2V4 representation of Mitrophanov2014 - Extended Hockin Blood Coagulation Model with additional fibrin-associated species 270.64 KB Preview | Download

Additional files

Mitrophanov2014.cps model COPASI file. 406.22 KB Preview | Download
figS2.pdf figure S2? 17.95 KB Preview | Download

  • Model originally submitted by : Matthew Roberts
  • Submitted: Jun 26, 2018 10:25:59 PM
  • Last Modified: Jun 26, 2018 10:25:59 PM
  • Version: 2 public model Download this version
    • Submitted on: Jun 26, 2018 10:25:59 PM
    • Submitted by: Matthew Roberts
    • With comment: Edited model metadata online.