Computational simulation of platelet deposition and activation: I. Model development and properties

To better understand the mechanisms leading to the formation and growth of mural thrombi on biomaterials, we have developed a two-dimensional computat ional model of platelet deposition and activation in flowing blood. The bas ic formulation is derived from prior work by others, with additional levels of complexity added where appropriate. It is comprised of a series of conv ection-diffusion-reaction equations which simulate platelet-surface and pla telet-platelet adhesion, platelet activation by a weighted linear combinati on of agonist concentrations, agonist release and synthesis by activated pl atelets, platelet-phospholipid-dependent thrombin generation, and thrombin inhibition by heparin. The model requires estimation of four parameters to fit it to experimental data: shear-dependent platelet diffusivity and resti ng and activated platelet-surface and platelet-platelet reaction rate const ants. The model is formulated to simulate a wide range of biomaterials and complex flows. In this article we present the basic model and its propertie s; in Part II (Sorensen et al., Ann. Biomed. Eng. 27:449-458, 1999) we appl y the model to experimental results for platelet deposition onto collagen. (C) 1999 Biomedical Engineering Society. [S0090-6964(99)01604-5].