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Blood, 1 May 2006, Vol. 107, No. 9, pp. 3537-3545. Prepublished online as a Blood First Edition Paper on January 31, 2006; DOI 10.1182/blood-2005-02-0618. This Article Full Text (PDF) Supplemental Videos All Versions of this Article: 2005-02-0618v1 107/9/3537    most recent Alert me when this article is cited Alert me if a correction is posted 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 Reininger, A. J Articles by Ruggeri, Z. M Search for Related Content PubMed PubMed Citation Articles by Reininger, A. J Articles by Ruggeri, Z. M Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 14, 2005 Accepted December 19, 2005 Mechanism of platelet adhesion to von Willebrand factor and microparticle formation under high shear stress Armin J Reininger*, Harry F Heijnen, Hannah Schumann, Hanno M Specht, Wolfgang Schramm, and Zaverio M Ruggeri Department of Transfusion Medicine and Hemostaseology, Clinic for Anesthesiology, University Clinic Munich, Ludwig-Maximilians-University, Munich, Germany Department of Hematology, Division of Thrombosis and Hemostasis, and Department of Cell Biology, University Medical Center, Utrecht, The Netherlands Roon Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA * Corresponding author; email: armin.reininger{at}med.uni-muenchen.de. We describe here the mechanism of platelet adhesion to immobilized von Willebrand factor (VWF) and subsequent formation of platelet-derived microparticles mediated by glycoprotein (GP) Ib under high shear stress. As visualized in whole blood perfused in a flow chamber, platelet attachment to VWF involved one or few membrane areas of 0.05-0.1 µm2 that formed discrete adhesion points (DAPs) capable of resisting force in excess of 160 pN. Under the influence of hydrodynamic drag, membrane tethers developed between the moving platelet body and DAPs firmly adherent to immobilized VWF. Continued stretching eventually caused the separation of many such tethers, leaving on the surface tube-shaped or spherical microparticles with a diameter as low as 50-100 nanometers. Adhesion receptors (GP Ib, IIb3) and phosphatidylserine were expressed on the surface of these microparticles, which were procoagulant. Shearing platelet-rich plasma at the rate of 10,000 s-1 in a cone-and-plate viscosimeter increased microparticle counts up to 55-fold above baseline. Blocking the GP Ib-VWF interaction abolished microparticle generation in both experimental conditions. Thus, a biomechanical process mediated by GP Ib-VWF bonds in rapidly flowing blood may not only initiate platelet arrest onto reactive vascular surfaces, but also generate procoagulant microparticles that further enhance thrombus formation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: "Pulling strings": shear, platelets, and microparticles Shaun P. Jackson, Pierre Mangin, and Yuping Yuan Blood 2006 107: 3418-3419. [Full Text] [PDF] This article has been cited by other articles: H. Cheng, R. Yan, S. Li, Y. Yuan, J. Liu, C. Ruan, and K. 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Orje, R. Habermann, A. B. Federici, and A. J. Reininger Activation-independent platelet adhesion and aggregation under elevated shear stress Blood, September 15, 2006; 108(6): 1903 - 1910. [Abstract] [Full Text] [PDF] C. M. Boulanger, N. Amabile, and A. Tedgui Circulating Microparticles: A Potential Prognostic Marker for Atherosclerotic Vascular Disease Hypertension, August 1, 2006; 48(2): 180 - 186. [Full Text] [PDF]

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