Evaluation and Calibration of In Silico Models of Thrombin Generation Using Experimental Data from Healthy and Haemophilic Subjects.
Bull Math Biol
; 80(8): 1989-2025, 2018 08.
Article
em En
| MEDLINE
| ID: mdl-29948884
ABSTRACT
The coagulation cascade comprises numerous chemical reactions between many proteins, that finally lead to the formation of a clot to stop bleeding. Many numerical models have attempted to translate understanding of this cascade into mathematical equations that simulate the chain reactions. However, their predictions have not been validated against clinical data stemming from patients. In this paper, we propose an extensive validation of five available models, by comparing in healthy and haemophilic subjects, thrombin generation measured in vitro to thrombin generation predicted by the models in silico. In order to render the models more predictive, we calibrated the models to have an acceptable agreement between the experimental and estimated data. Optimization processes based on genetic algorithms were developed to search for those calibrated kinetic parameters. Our results show that the thrombin generation kinetics are so complex that they cannot be predicted by a unique set of kinetic parameters for all patients the calibration of only three parameters in a subject-specific way allows reaching good model estimations for different experimental conditions realized on the same patient.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Trombina
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Hemofilia A
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Modelos Biológicos
Tipo de estudo:
Evaluation_studies
/
Prognostic_studies
Limite:
Humans
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Male
Idioma:
En
Revista:
Bull Math Biol
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
França