Brummel-Ziedins2012 - Contribution of the PC pathway to thrombin generation
Ontology highlight
ABSTRACT:
SUBMITTER: 
Matthew Roberts
PROVIDER: MODEL1807180002 | BioModels | 2018-07-18
REPOSITORIES: BioModels
Dataset's files
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Publications
The prothrombotic phenotypes in familial protein C deficiency are differentiated by computational modeling of thrombin generation.
Brummel-Ziedins Kathleen E KE Orfeo Thomas T Callas Peter W PW Gissel Matthew M Mann Kenneth G KG Bovill Edwin G EG
PloS one 20120912 9
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 gener ...[more]
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Project description:Jones1994_BloodCoagulation
This model is built based on the
experimental findings described in Lawson et al., 1994
(PMID:8083241)
This model is described in the article:
A model for the
tissue factor pathway to thrombin. II. A mathematical
simulation.
Jones KC, Mann KG.
J. Biol. Chem. 1994 Sep; 269(37):
23367-23373
Abstract:
A mathematical simulation of the tissue factor pathway to
the generation of thrombin has been developed using a
combination of empirical, estimated, and deduced rate constants
for reactions involving the activation of factor IX, X, V, and
VIII, in the formation of thrombin, as well as rate constants
for the assembly of the coagulation enzyme complexes which
involve factor VIIIa-factor IXa (intrinsic tenase) and factor
Va-Xa (prothrombinase) assembled on phospholipid membrane.
Differential equations describing the fate of each species in
the reaction were developed and solved using an interactive
procedure based upon the Runge-Kutta technique. In addition to
the theoretical considerations involving the reactions of the
tissue factor pathway, a physical constraint associated with
the stability of the factor VIIIa-factor IXa complex has been
incorporated into the model based upon the empirical
observations associated with the stability of this complex. The
model system provides a realistic accounting of the fates of
each of the proteins in the coagulation reaction through a
range of initiator (factor VIIa-tissue factor) concentrations
ranging from 5 pM to 5 nM. The model is responsive to
alterations in the concentrations of factor VIII, factor V, and
their respective activated species, factor VIIIa and factor Va,
and overall provides a reasonable approximation of empirical
data. The computer model permits the assessment of the reaction
over a broad range of conditions and provides a useful tool for
the development and management of reaction studies.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000336.
To cite BioModels Database, please use:
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To the extent possible under law, all copyright and related or
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CC0
Public Domain Dedication for more information.
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