Integrating blood cell mechanics, platelet adhesive dynamics and coagulation cascade for modelling thrombus formation in normal and diabetic blood

Abstract

Normal haemostasis is an important physiological mechanism that prevents excessive bleeding during trauma, whereas the pathological thrombosis especially in diabetics leads to increased incidence of heart attacks and strokes as well as peripheral vascular events. In this work, we propose a new multiscale framework that integrates seamlessly four key components of blood clotting, namely transport of coagulation factors, coagulation kinetics, blood cell mechanics and platelet adhesive dynamics, to model the development of thrombi under physiological and pathological conditions. We implement this framework to simulate platelet adhesion due to the exposure of tissue factor in a three-dimensional microchannel. Our results show that our model can simulate thrombin-mediated platelet activation in the flowing blood, resulting in platelet adhesion to the injury site of the channel wall. Furthermore, we simulate platelet adhesion in diabetic blood, and our results show that both the pathological alterations in the biomechanics of blood cells and changes in the amount of coagulation factors contribute to the excessive platelet adhesion and aggregation in diabetic blood. Taken together, this new framework can be used to probe synergistic mechanisms of thrombus formation under physiological and pathological conditions, and open new directions in modelling complex biological problems that involve several multiscale processes.

Delivery of Nitric Oxide in the Cardiovascular System: Implications for Clinical Diagnosis and Therapy

“…The complex arterial mass delivery process is difficult to experimentally investigate in vivo, and computational modeling of the process has been widely accepted as a powerful tool for studying the delivery of low-density lipoproteins [35,36] and thrombus [37,38]. The unique advantage of computational modeling is the capability to control physiological parameters quantitatively; therefore, confounding factors that affect analysis can be eliminated.…”

Recent Advances in Computational Modeling of Biomechanics and Biorheology of Red Blood Cells in Diabetes

“…The author employed a stochastic bond formation–rupture model proposed by Mody and King [ 107 ] to consider the adhesive dynamics of receptors on the platelet membrane binding to their ligands. A detailed description of the adhesive dynamics model can be found in the original paper [ 104 ].…”

“…In addition to examining the effect of the altered biomechanics of blood cells in promoting platelet aggregation, the authors of [ 104 ] also investigate the impact of abnormal coagulation factors in the diabetes on exacerbating thrombus formation. Following the study of [ 109 ], the authors select the concentration of plasma fibrinogen, a key source of fibrin in the circulating blood, to be higher than normal blood.…”

“…Solvent particles in the simulate carry 22 species for modeling the coagulation cascade that is initiated from two injury sites (highlighted with blue color lines) with a size of 40 m located at the upper and bottom channel wall respectively. Figure is reproduced from [ 104 ].…”

The Delivery of Nitric Oxide in the Cardiovascular System: Implication for Clinical Diagnosis and Therapy

“…The complex arterial mass delivery process is hard to experimentally investigate in vivo, and mathematical analysis of the process has been widely accepted as a powerful tool for studying the delivery of low-density lipoprotein [36][37][38] and thrombus [39][40][41]. However, due to the low concentration (nM-μM) and high chemical activity natures, the process of NO delivery is quite different from the above substances: the production, transmission and reaction processes are all nonnegligible and should be simultaneously simulated.…”