Effect of Hemodynamic Forces on Platelet Aggregation Geometry

The shear rate dependence of platelet aggregation geometries is investigated using a combination of in vitro and numerical experiments. Changes in upstream shear rate, γPw, are found to cause systematic changes in mature platelet aggregation geometries. However, γPw is not the only factor determining the shear rate experienced by a platelet moving over, and adhering to, a platelet aggregation: flow simulations demonstrate that naturally occurring variations in platelet aggregation geometry cause the local shear rate on the surface of a mature platelet aggregation to vary between zero and up to eight times γPw. Additionally, as a platelet aggregation grows, systematic changes in geometry are found, indicating that the local shear field over a growing platelet aggregation will differ from that over mature platelet aggregations.

[1]  Arnan Mitchell,et al.  A shear gradient–dependent platelet aggregation mechanism drives thrombus formation , 2009, Nature Medicine.

[2]  T. Papanastasiou,et al.  Viscous Fluid Flow , 1999 .

[3]  Z. Ruggeri,et al.  Activation of Platelet Function Through G Protein–Coupled Receptors Platelets As Immune Cells: Bridging Inflammation and Cardiovascular Disease In Vivo Thrombus Formation in Murine Models Clinical Aspects of Platelet Inhibitors and Thrombus Formation Adhesion Mechanisms in Platelet Function , 2007 .

[4]  Eric J. Topol,et al.  Scientific and therapeutic advances in antiplatelet therapy , 2003, Nature Reviews Drug Discovery.

[5]  R. Ross,et al.  The pathogenesis of atherosclerosis (first of two parts). , 1976, The New England journal of medicine.

[6]  K. Ley,et al.  Role of platelets in the development of atherosclerosis. , 2004, Trends in cardiovascular medicine.

[7]  Andreas Fouras,et al.  Volumetric correlation PIV: a new technique for 3D velocity vector field measurement , 2009 .

[8]  Y. Fung,et al.  Biomechanics: Mechanical Properties of Living Tissues , 1981 .

[9]  Zaverio M. Ruggeri,et al.  Platelets in atherothrombosis , 2002, Nature Medicine.

[10]  Z. Ruggeri,et al.  The role of von Willebrand factor in thrombus formation. , 2007, Thrombosis research.

[11]  Brian Savage,et al.  Specific Synergy of Multiple Substrate–Receptor Interactions in Platelet Thrombus Formation under Flow , 1998, Cell.

[12]  Shaun P Jackson,et al.  The growing complexity of platelet aggregation. , 2007, Blood.

[13]  S. Hsiao,et al.  Identification of a fibrin-independent platelet contractile mechanism regulating primary hemostasis and thrombus growth. , 2008, Blood.

[14]  Warwick S Nesbitt,et al.  Identification of a 2-stage platelet aggregation process mediating shear-dependent thrombus formation. , 2007, Blood.

[15]  Erling Falk,et al.  Pathogenesis of atherosclerosis. , 2006, Journal of the American College of Cardiology.

[16]  S. Jackson,et al.  Thrombin overcomes the thrombosis defect associated with platelet GPVI/FcRgamma deficiency. , 2006, Blood.