A hybrid-system model of the coagulation cascade: simulation, sensitivity, and validation

Area of Science:

• Biophysics
• Computational Biology
• Systems Biology

Background:

• Human blood clotting is a complex cascade involving continuous chemical reactions and discrete events.
• Previous models primarily used continuous dynamics, limiting their ability to capture the full clotting process.

Purpose of the Study:

• To develop a comprehensive model of blood clotting that integrates both continuous and discrete dynamical aspects.
• To utilize a hybrid dynamical system approach for enhanced simulation and prediction of clotting phenomena.

Main Methods:

• Modeled blood clotting as a hybrid dynamical system.
• Implemented the model using a hybrid Petri net, extending ordinary Petri nets for continuous flows and quantities.
• Focused on simulation fidelity, reproduction of pathologies, and fine-grained predictions.

Main Results:

• The hybrid Petri net model successfully captures both continuous and discrete aspects of blood clotting.
• Simulations demonstrated fidelity to clinical data regarding clotting factors and time.
• The model reproduced known clotting pathologies and offered potential for refined clinical understanding.

Conclusions:

• Hybrid dynamical systems offer a powerful framework for modeling complex biological processes like blood clotting.
• The developed hybrid Petri net model provides a more accurate and comprehensive representation of coagulation.
• This approach facilitates improved simulation, prediction, and understanding of blood clotting mechanisms and pathologies.