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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 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 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 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 Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Mechanism of platelet adhesion to von Willebrand factor and microparticle formation under high shear stress Armin J. Reininger, Harry F. G. Heijnen, Hannah Schumann, Hanno M. Specht, Wolfgang Schramm, and Zaverio M. Ruggeri From the Department of Transfusion Medicine and Hemostaseology, Clinic for Anesthesiology, University Clinic Munich, Ludwig-Maximilians-University, Munich, Germany; the Department of Hematology, Division of Thrombosis and Hemostasis, University Medical Center Utrecht, Utrecht, the Netherlands; the Department of Cell Biology, University Medical Center Utrecht, Utrecht, the Netherlands; and the 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. We describe here the mechanism of platelet adhesion to immobilized von Willebrand factor (VWF) and subsequent formation of platelet-derived microparticles mediated by glycoprotein Ib (GPIb) 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 to 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 to 100 nm. Adhesion receptors (GPIb, 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 GPIb-VWF interaction abolished microparticle generation in both experimental conditions. Thus, a biomechanical process mediated by GPIb-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: F. Rodeghiero, G. Castaman, and A. Tosetto How I treat von Willebrand disease Blood, August 6, 2009; 114(6): 1158 - 1165. [Abstract] [Full Text] [PDF] C. Kleinschnitz, S. F. De Meyer, T. Schwarz, M. Austinat, K. Vanhoorelbeke, B. Nieswandt, H. Deckmyn, and G. Stoll Deficiency of von Willebrand factor protects mice from ischemic stroke Blood, April 9, 2009; 113(15): 3600 - 3603. [Abstract] [Full Text] [PDF] L. Ayers, B. Ferry, S. Craig, D. Nicoll, J. R. Stradling, and M. Kohler Circulating cell-derived microparticles in patients with minimally symptomatic obstructive sleep apnoea Eur. Respir. J., March 1, 2009; 33(3): 574 - 580. [Abstract] [Full Text] [PDF] A. O. Spiel, J. C. Gilbert, and B. Jilma Von Willebrand Factor in Cardiovascular Disease: Focus on Acute Coronary Syndromes Circulation, March 18, 2008; 117(11): 1449 - 1459. [Abstract] [Full Text] [PDF] J. C. Gilbert, T. DeFeo-Fraulini, R. M. Hutabarat, C. J. Horvath, P. G. Merlino, H. N. Marsh, J. M. Healy, S. BouFakhreddine, T. V. Holohan, and R. G. Schaub First-in-Human Evaluation of Anti von Willebrand Factor Therapeutic Aptamer ARC1779 in Healthy Volunteers Circulation, December 4, 2007; 116(23): 2678 - 2686. [Abstract] [Full Text] [PDF] S. P. Jackson The growing complexity of platelet aggregation Blood, June 15, 2007; 109(12): 5087 - 5095. [Abstract] [Full Text] [PDF] H. Schwertz, N. D. Tolley, J. M. Foulks, M. M. Denis, B. W. Risenmay, M. Buerke, R. E. Tilley, M. T. Rondina, E. M. Harris, L. W. Kraiss, et al. Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenecity of human platelets J. Exp. Med., October 30, 2006; 203(11): 2433 - 2440. [Abstract] [Full Text] [PDF] Z. M. Ruggeri, J. N. 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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