FEIT Research Project Database

Modelling the coagulation cascade

Project Leader: Joe Berry
Staff: Dalton Harvie
Primary Contact: Dalton Harvie (daltonh@unimelb.edu.au)
Keywords: chemical reaction kinetics; complex systems; computational biology; computational fluid dynamics
Disciplines: Chemical & Biomolecular Engineering
Domains: Convergence of engineering and IT with the life sciences

Upon injury to a blood vessel, platelets activate and attach to the site of the injury in order to form a “plug” (or clot) to repair the damage. At the instant of injury, exposure of sub-endothelial tissue factor triggers a complex coagulation cascade in order to produce fibrin, the “glue” that holds the clot together. The coagulation cascade consists of two pathways, the intrinsic (contact activation) pathway, and the extrinsic (or tissue factor) pathway.  The pathways consist of a series of reactions whereby proteins become activated in order to catalyse the next reaction in the cascade. Literature values for the kinetic rate parameters of these reactions vary over several orders of magnitude. While the sensitivity of thrombin generation models to the uncertainties in kinetic parameters has been studied for static systems, this sensitivity is greatly amplified in flowing systems.

The project involves the development of numerical models to describe the coagulation cascade in flowing systems, building upon existing biochemical continuum models. This project sits within a larger collaborative project involving experimentalists and modellers from the University of Melbourne, RMIT and CSL, and offers a unique opportunity to make a significant impact in the modelling of a critically important biological function.