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Prepublished online as a Blood First Edition Paper on November 27, 2002; DOI 10.1182/blood-2002-05-1550. This Article Full Text Full Text (PDF) Supplemental PDF All Versions of this Article: 2002-05-1550v1 101/7/2637    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Shankaran, H. Articles by Neelamegham, S. Search for Related Content PubMed PubMed Citation Articles by Shankaran, H. Articles by Neelamegham, S. Related Collections Hemostasis, Thrombosis, and Vascular Biology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 April 2003, Vol. 101, No. 7, pp. 2637-2645 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Aspects of hydrodynamic shear regulating shear-induced platelet activation and self-association of von Willebrand factor in suspension Harish Shankaran, Paschalis Alexandridis, and Sriram Neelamegham From the Bioengineering Laboratory, Department of Chemical Engineering, State University of New York at Buffalo, NY. The binding of plasma von Willebrand factor (VWF) to platelet receptor GpIb under high hydrodynamic shear leads to platelet activation and subsequent shear-induced platelet aggregation (SIPA). We quantitatively examined the aspects of fluid flow that regulate platelet activation by subjecting human blood and isolated platelets to well-defined shear conditions in a cone-plate viscometer. We made the following observations. First, Annexin V binding to phosphatidyl serine expressed on activated cells was detectable within 10 seconds of shear application. Second, fluid shear stress rather than shear rate controls platelet activation, and a threshold shear stress of approximately 80 dyn/cm2 is necessary to induce significant activation. Under these conditions, individual domains of soluble VWF and platelet GpIb are subjected to similar magnitudes of fluid forces on the order of 0.1 pN, whereas GpIb with bound VWF is subjected to 1 pN. Third, cell-cell collisions and time-varying stresses are not essential for platelet activation. Fourth, the mechanism of platelet activation can be resolved in 2 steps based on the contribution of VWF and fluid forces. Fluid shear and VWF are required during the first step, when GpIb-VWF binding likely occurs. Subsequently, high shear forces alone in the absence of VWF in suspension can induce platelet activation. In other experiments, purified VWF was subjected to shear in the viscometer, and VWF morphology was assessed using light scattering. These studies demonstrate, for the first time, the ability of hydrodynamic forces to induce VWF aggregation in suspension. This VWF self-association may be an additional feature involved in controlling cell adhesion rates in circulation. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. K. Mishra, J. Kovac, J. de Caestecker, G. Fancourt, E. Logtens, and T. Spyt Intestinal angiodysplasia and aortic valve stenosis: let's not close the book on this association Eur. J. Cardiothorac. Surg., April 1, 2009; 35(4): 628 - 634. [Abstract] [Full Text] [PDF] J. Huang, R. Roth, J. E. Heuser, and J. E. 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