CiteULike: matthewhflamm deposition

Computational Simulation of Platelet Deposition and Activation: II. Results for Poiseuille Flow over Collagen

Erik Sorensen — 2008-04-17T18:17:08-00:00

Annals of Biomedical Engineering, Vol. 27, No. 4. (1 July 1999), pp. 449-458.

We have previously described the development of a two-dimensional computational model of platelet deposition onto biomaterials from flowing blood (Sorensen et al., Ann. Biomed. Eng. 27:436–448, 1999). The model requires estimation of four parameters to fit it to experimental data: shear-dependent platelet diffusivity and three platelet-deposition-related reaction rate constants. These parameters are estimated for platelet deposition onto a collagen substrate for simple parallel-plate flow of whole blood in both the presence and absence of thrombin. One set of experimental results is used as a benchmark for model-fitting purposes. The “trained” model is then validated by applying it to additional test cases from the literature for parallel-plate Poiseuille flow over collagen at both higher and lower wall shear rates, and in the presence of various anticoagulants. The predicted values agree very well with the experimental results for the training cases, and good reproduction of deposition trends and magnitudes is obtained for the heparin, but not the citrate, validation cases. The model is formulated to be easily extended to synthetic biomaterials, as well as to more complex flows. © 1999 Biomedical Engineering Society.

Computational Simulation of Platelet Deposition and Activation: I. Model Development and Properties

Erik Sorensen — 2008-04-17T18:16:07-00:00

Annals of Biomedical Engineering, Vol. 27, No. 4. (1 July 1999), pp. 436-448.

To better understand the mechanisms leading to the formation and growth of mural thrombi on biomaterials, we have developed a two-dimensional computational model of platelet deposition and activation in flowing blood. The basic formulation is derived from prior work by others, with additional levels of complexity added where appropriate. It is comprised of a series of convection-diffusion-reaction equations which simulate platelet-surface and platelet-platelet adhesion, platelet activation by a weighted linear combination of agonist concentrations, agonist release and synthesis by activated platelets, 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 resting and activated platelet-surface and platelet-platelet reaction rate constants. The model is formulated to simulate a wide range of biomaterials and complex flows. In this article we present the basic model and its properties; in Part II (Sorensen et al., Ann. Biomed. Eng. 27:449–458, 1999) we apply the model to experimental results for platelet deposition onto collagen. © 1999 Biomedical Engineering Society.

Boundary-layer Type Solutions for Initial Platelet Activation and Deposition

T David — 2008-04-17T18:14:27-00:00

Journal of Theoretical Medicine (January 2002), pp. 95-108.

This paper presents, on the basis of high Peclet number, a mathematical model for the activation and initial adhesion of flowing platelets onto a surface. In contrast to past work, the model is applicable to general 2D and axi-symmetric flows where the wall shear stress is known a priori. Results indicate that for high activation reaction rates there exist two layers, one containing only activated platelets and the other both activated and non-activated platelets. Fundamental relationships are proposed between the adhesion rate of platelets to the surface and the characteristic parameters of Peclet number and Reynolds number. Activation in the bulk fluid (blood) is characterised by the Damkohler number, which is a function of activation rate and the free-stream velocity. It is shown that, as the free-stream velocity varies, there exists a maximum of activated platelet flux to the wall for particular values of the velocity. These values, at which the maximum occur, are themselves functions of the platelet activation rate. As the free-stream velocity increases the activation of platelets ceases altogether and adhesion is reduced to a very small value strengthening the hypothesis of the correlation between atherogenesis/thrombogenesis and areas of low shear.

Surface-Mediated Control of Blood Coagulation: The Role of Binding Site Densities and Platelet Deposition

Andrew Kuharsky — 2008-03-27T18:00:29-00:00

Biophys. J., Vol. 80, No. 3. (1 March 2001), pp. 1050-1074.

A mathematical model of the extrinsic or tissue factor (TF) pathway of blood coagulation is formulated and results from a computational study of its behavior are presented. The model takes into account plasma-phase and surface-bound enzymes and zymogens, coagulation inhibitors, and activated and unactivated platelets. It includes both plasma-phase and membrane-phase reactions, and accounts for chemical and cellular transport by flow and diffusion, albeit in a simplified manner by assuming the existence of a thin, well-mixed fluid layer, near the surface, whose thickness depends on flow. There are three main conclusions from these studies. (i) The model system responds in a threshold manner to changes in the availability of particular surface binding sites; an increase in TF binding sites, as would occur with vascular injury, changes the system's production of thrombin dramatically. (ii) The model suggests that platelets adhering to and covering the subendothelium, rather than chemical inhibitors, may play the dominant role in blocking the activity of the TF:VIIa enzyme complex. This, in turn, suggests that a role of the IXa-tenase pathway for activating factor X to Xa is to continue factor Xa production after platelets have covered the TF:VIIa complexes on the subendothelium. (iii) The model gives a kinetic explanation of the reduced thrombin production in hemophilias A and B.