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Nayak2015 - Blood Coagulation Network - Predicting the Effects of Various Therapies on Biomarkers


ABSTRACT: Nayak2015 - Blood Coagulation Network - Predicting the Effects of Various Therapies on Biomarkers Note: The SBML model is generated from SimBiology. The SimBiology (.sbproj) file is available for download from the curation tab. This model is described in the article: Using a Systems Pharmacology Model of the Blood Coagulation Network to Predict the Effects of Various Therapies on Biomarkers. Nayak S, Lee D, Patel-Hett S, Pittman DD, Martin SW, Heatherington AC, Vicini P, Hua F. CPT Pharmacometrics Syst Pharmacol. 2015 Jul;4(7):396-405. Abstract: A number of therapeutics have been developed or are under development aiming to modulate the coagulation network to treat various diseases. We used a systems model to better understand the effect of modulating various components on blood coagulation. A computational model of the coagulation network was built to match in-house in vitro thrombin generation and activated Partial Thromboplastin Time (aPTT) data with various concentrations of recombinant factor VIIa (FVIIa) or factor Xa added to normal human plasma or factor VIII-deficient plasma. Sensitivity analysis applied to the model revealed that lag time, peak thrombin concentration, area under the curve (AUC) of the thrombin generation profile, and aPTT show different sensitivity to changes in coagulation factors' concentrations and type of plasma used (normal or factor VIII-deficient). We also used the model to explore how variability in concentrations of the proteins in coagulation network can impact the response to FVIIa treatment. This model is hosted on BioModels Database and identified by: MODEL1511160000. To cite BioModels Database, please use: BioModels: Content, Features, Functionality and Use. 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.

DISEASE(S): Blood Coagulation Disease

SUBMITTER: Satyaprakash Nayak  

PROVIDER: BIOMD0000000611 | BioModels | 2015-12-08

REPOSITORIES: BioModels

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Using a Systems Pharmacology Model of the Blood Coagulation Network to Predict the Effects of Various Therapies on Biomarkers.

Nayak S S   Lee D D   Patel-Hett S S   Pittman D D DD   Martin S W SW   Heatherington A C AC   Vicini P P   Hua F F  

CPT: pharmacometrics & systems pharmacology 20150619 7


A number of therapeutics have been developed or are under development aiming to modulate the coagulation network to treat various diseases. We used a systems model to better understand the effect of modulating various components on blood coagulation. A computational model of the coagulation network was built to match in-house in vitro thrombin generation and activated Partial Thromboplastin Time (aPTT) data with various concentrations of recombinant factor VIIa (FVIIa) or factor Xa added to norm  ...[more]

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