Modelling fibrinolysis: 1D continuum models

Abstract

Fibrinolysis is the enzymatic degradation of the fibrin mesh that stabilizes blood clots. Experiments have shown that coarse clots made of thick fibres sometimes lyse more quickly than fine clots made of thin fibres, despite the fact that individual thick fibres lyse more slowly than individual thin fibres. This paper aims at using a 1D continuum reaction–diffusion model of fibrinolysis to elucidate the mechanism by which coarse clots lyse more quickly than fine clots. Reaction–diffusion models have been the standard tool for investigating fibrinolysis, and have been successful in capturing the wave-like behaviour of lysis seen in experiments. These previous models treat the distribution of fibrin within a clot as homogeneous, and therefore cannot be used directly to study the lysis of fine and coarse clots. In our model, we include a spatially heterogeneous fibrin concentration, as well as a more accurate description of the role of fibrin as a cofactor in the activation of the lytic enzyme. Our model predicts spatio-temporal protein distributions in reasonable quantitative agreement with experimental data. The model also predicts observed behaviour such as a front of lysis moving through the clot with an accumulation of lytic proteins at the front. In spite of the model improvements, however, we find that 1D continuum models are unable to accurately describe the observed differences in lysis behaviour between fine and coarse clots. Features of the problems that lead to the inaccuracy of 1D continuum models are discussed. We conclude that higher-dimensional, multiscale models are required to investigate the effect of clot structure on lysis behaviour.