Computational study of plasma protein adsorption and coagulation factors involved in thrombogenesis on blood contact surfaces

Abstract

The exposure of any material to blood leads to the adsorption of proteins onto its surface resulting in formation of clot which adversely affects the functionality of the blood contacting device. Adsorption of protein leads to two major consequences- platelet aggregation on the implant surface and generation of fibrin in blood; together platelet and fibrin form thrombus (clot). The main objective of this study was to investigate the thrombogenic potentiality of a blood-contact surface via computational techniques. Two mathematical models were developed- one to determine plasma protein adsorption pattern and subsequent platelet activation on an implant surface, and the other model was developed for the generation of fibrin by intrinsic coagulation pathway. In the first model for simulation of protein adsorption, composition of blood, adsorption and desorption of major blood proteins- albumin and fibrinogen, exchange of proteins from bulk to surface, conformational changes of proteins upon adsorption and platelet activation due to the presence of fibrinogen were considered for modelling. Simulation of the system of differential equations involving these factors were conducted in MATLAB with appropriate kinetic parameters and boundary conditions. The surface coverage along with concentration profiles of albumin and fibrinogen and effect of change in adsorbed protein relaxation rate on platelet activation obtained from simulation were listed and compared with results the previously developed models. For the second model for coagulation pathway simulation, twenty-five differential equations were deduced using the Michaelis–Menten approach for different coagulation factors and inhibitors. The concentration profiles of important factors and major inhibitors obtained from simulation were listed and compared with literature data. This model was also used to inspect the tendency of thrombin generation in case of a deficiency of any inhibitor. It was found that the trends of the concentration profiles of major factors of this study reasonably match with those of previous models. Both of these models can be useful for the analysis of the regulation of the clot formation and engineering non-thrombogenic surfaces for better biocompatible blood contacting devices.