Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Matthew Roberts

PROVIDER: MODEL1807180002 | BioModels | 2018-07-18

REPOSITORIES: BioModels

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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]

PMID: 22984498

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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: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:Stortelder1997 - Thrombin Generation Amidolytic Activity Mathematical modelling of a part of the blood coagulation mechanism. This model is described in the article: Mathematical modelling in blood coagulation : simulation and parameter estimation. Stortelder W.J.H., Hemker P.W., Hemker, H.C. CWI. Modelling, Analysis and Simulation, No. R 9720, p.1-11. Abstract: This paper describes the mathematical modelling of a part of the blood coagulation mechanism. The model includes the activation of factor X by a purified enzyme from Russel's Viper Venom (RVV), factor V and prothrombin, and also comprises the inactivation of the products formed. In this study we assume that in principle the mechanism of the process is known. However, the exact structure of the mechanism is unknown, and the process still can be described by different mathematical models. These models are put to test by measuring their capacity to explain the course of thrombin generation as observed in plasma after recalcification in presence of RVV. The mechanism studied is mathematically modelled as a system of differential-algebraic equations (DAEs). Each candidate model contains some freedom, which is expressed in the model equations by the presence of unknown parameters. For example, reaction constants or initial concentrations are unknown. The goal of parameter estimation is to determine these unknown parameters in such a way that the theoretical (i.e., computed) results fit the experimental data within measurement accuracy and to judge which modifications of the chemical reaction scheme allow the best fit. We present results on model discrimination and estimation of reaction constants, which are hard to obtain in another way. This model is hosted on BioModels Database and identified by: BIOMD0000000358 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

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

Publications

The prothrombotic phenotypes in familial protein C deficiency are differentiated by computational modeling of thrombin generation.

Similar Datasets

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