CiteULike: matthewhflamm computational_simulation

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.

Blood flow velocity effects and role of activation delay time on growth and form of platelet thrombi

Igor Pivkin — 2008-04-17T17:52:05-00:00

Proceedings of the National Academy of Sciences, Vol. 103, No. 46. (14 November 2006), pp. 17164-17169.

Mural thrombi are composed dominantly of platelets and develop under a blood flow. Portions can break off and are carried in the blood flow as emboli. Thrombus growth rates are affected by the velocity of the blood flow, but they do not simply increase with it, they exhibit a maximum, with subsequent decrease. Whereas this variation indicates an interaction of biochemical and physical processes, studies have concentrated widely on understanding only the biochemical processes. Here we show results of simulation of thrombus formation in 3D flows by accounting for the movements of individual platelets. Each platelet follows prescribed rules for interactions while the local flow around the thrombus continuously adjusts to the growing structure of the thrombus, also when embolization occurs. With an activation delay time assigned to each platelet we demonstrate the dependence of thrombus growth rate on blood velocity as found experimentally by Begent and Born [Begent N, Born GV (1970) Nature 227:926-930]. With activated platelets having mutual tensile action sustainable up to a prescribed distance we achieve thrombus growth faster than with shorter maximum distances that make a thrombus less porous; when the prescribed maximum distance is large enough the thrombus shape is not like a "hill" but like a "carpet." We find that thrombus growth rate is enhanced by modest pulsatility but less so when pulsations are amplified in part because of more embolization. 10.1073/pnas.0608546103

Simulation of platelet adhesion and aggregation regulated by fibrinogen and von Willebrand factor

Daisuke Mori — 2008-04-17T17:43:29-00:00

Thrombosis and Haemostasis, Vol. 99, No. 1. (January 2008), pp. 108-115.

We propose a method to analyze platelet adhesion and aggregation computationally, taking into account the distinct properties of two plasma proteins, vonWillebrand factor (vWF) and fibrinogen (Fbg). In this method, the hydrodynamic interactions between platelet particles under simple shear flow were simulated using Stokesian dynamics based on the additivity of velocities. The binding force between particles mediated by vWF and Fbg was modeled using the Voigt model.Two Voigt models with different properties were introduced to consider the distinct behaviors of vWF and Fbg. Our results qualitatively agreed with the general observation of a previous in-vitro experiment, thus demonstrating that the significant development of thrombus formation in height requires not only vWF, but also Fbg. This agreement of simulation and experimental results qualitatively validates our model and suggests that consideration of the distinct roles of vWF and Fbg is essential to investigate the physiological and pathophysiological mechanisms of thrombus formation using a computational approach.