Brummel-Ziedins2012 - Contribution of the PC pathway to thrombin generation

  public model
Model Identifier
Short description
Mathematical model of the blood coagulation cascade including meizothrombin, protein C, thrombomodulin, factor VIIIa fragments, partially proteolyzed factor Va species and inactive factor Va fragments.
Related Publication
  • The prothrombotic phenotypes in familial protein C deficiency are differentiated by computational modeling of thrombin generation.
  • Brummel-Ziedins KE, Orfeo T, Callas PW, Gissel M, Mann KG, Bovill EG
  • PloS one , 1/ 2012 , Volume 7 , Issue 9 , pages: e44378 , PubMed ID: 22984498
  • Department of Biochemistry, University of Vermont, College of Medicine, Burlington, Vermont, United States of America.
  • The underlying cause of thrombosis in a large protein C (PC) deficient Vermont kindred appears to be multicausal and not explained by PC deficiency alone. We evaluated the contribution of coagulation factors to thrombin generation in this population utilizing a mathematical model that incorporates a mechanistic description of the PC pathway. Thrombin generation profiles for each individual were generated with and without the contribution of the PC pathway. Parameters that describe thrombin generation: maximum level (MaxL) and rate (MaxR), their respective times (TMaxL, TMaxR), area under the curve (AUC) and clotting time (CT) were examined in individuals ± PC mutation, ± prothrombin G20210A polymorphism and ± thrombosis history (DVT or PE). This family (n = 364) is shifted towards greater thrombin generation relative to the mean physiologic control. When this family was analyzed with the PC pathway, our results showed that: carriers of the PC mutation (n = 81) had higher MaxL and MaxR and greater AUC (all p<0.001) than non-carriers (n = 283); and individuals with a DVT and/or PE history (n = 13) had higher MaxL (p = 0.005) and greater AUC (p<0.001) than individuals without a thrombosis history (n = 351). These differences were further stratified by gender, with women in all categories generating more thrombin than males. These results show that all individuals within this family with or without PC deficiency have an increased baseline procoagulant potential reflective of increased thrombin generation. In addition, variations within the plasma composition of each individual can further segregate out increased procoagulant phenotypes, with gender-associated plasma compositional differences playing a large role.
Submitter of the first revision: Matthew Roberts
Submitter of this revision: Matthew Roberts
Modellers: Matthew Roberts

Metadata information

isDescribedBy (1 statement)
PubMed 22984498

isVersionOf (1 statement)
Gene Ontology blood coagulation

Curation status


Connected external resources

SBGN view in Newt Editor

Name Description Size Actions

Model files

Brummel-Ziedins2012.xml SBML L2V4 representation of Brummel-Ziedins2012 - Contribution of the PC pathway to thrombin generation 115.62 KB Preview | Download

Additional files

Brummel-Ziedins2012.cps Model COPASI file. Attempt at reproducing gold curve (thrombin - IIa) in figure 1. Reactions and kinetic rates given in supplementary files. Physiological mean in table I was used as the initial conditions. 256.74 KB Preview | Download

  • Model originally submitted by : Matthew Roberts
  • Submitted: Jul 18, 2018 9:36:54 AM
  • Last Modified: Jul 18, 2018 9:36:54 AM
  • Version: 2 public model Download this version
    • Submitted on: Jul 18, 2018 9:36:54 AM
    • Submitted by: Matthew Roberts
    • With comment: Edited model metadata online.