Transport-reaction model of mural thrombogenesis: comparisons of mathematical model predictions and results from baboon models

Abstract

Thrombogenesis depends on biochemical reactions affected by blood flow dynamics. While mathematical models of mural thrombogenesis provide a means of understanding how blood flow affects thrombus growth, comparisons to experimental data are needed to validate the models and enable prediction of thrombus growth under diverse conditions. In this paper, we present mathematical models of mural thrombogenesis under flow and validation of the models with experimental data collected from a thrombogenic vascular graft segment. The grafts were placed in exteriorized high-flow arteriovenous (AV) shunts in baboons. Radiolabeled platelet deposition onto the thrombogenic segment, a marker of thrombus size, and plasma thrombin-antithrombin (TAT) concentration downstream of the graft, a marker of local thrombin generation, were monitored over time. The mathematical model of mural thrombogenesis consisted of transport-reaction equations in which platelets and thrombin were explicitly considered. We found that the transport-reaction model captured the order of magnitude of TAT sampled levels, while calculated rates of platelet deposition agreed well with radioimaging results. Analysis of experimental and modeling data indicates that, at least during part of thrombus growth progression, thrombin generation is in excess and platelet adhesion rates would be sustained even at lower local thrombin concentrations.