Model reduction of coagulation cascade based on genetic algorithm

Fibrin is an important product of the coagulation cascade, and plays an eminent role in platelet stabilization. Since coagulation cascade models typically involve the reaction kinetics of dozens of proteins, which will incur burdensome computational costs when coupled to blood flow in complex geometries, researchers often ignore this process when constructing thrombosis models. However, previous studies have shown that fundamental aspects of coagulation can be reproduced with simpler models, which motivated us to obtain a reduced-order model of fibrin generation through a systematic approach. Therefore, we introduced a semi-automatic framework to perform model-reduction of cascade reactions in this study, which consisted of two processes. Specifically, the retained protein species and cascade reactions were determined based on published studies and simulation results from the full cascade model, while the optimal reaction rates for the new cascade network were determined using a genetic algorithm. The framework has been applied to a 19-species coagulation model that triggers fibrin generation in internal fields via reactive boundaries, and a 10-species reduced-order model was obtained to reproduce the kinetics of fibrinogenesis in the full cascade model at different boundary tissue factor concentrations. This reduced-order model of fibrinogenesis would be valuable for thrombosis modeling that considers both the coagulation cascade and platelet activity. Furthermore, the framework proposed herein can also be applied to the reductions of other cascade reaction models.