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Blood, 15 September 2006, Vol. 108, No. 6, pp. 1903-1910. Prepublished online as a Blood First Edition Paper on June 13, 2006; DOI 10.1182/blood-2006-04-011551. This Article Full Text Full Text (PDF) Supplemental Methods and Videos Additional Supplemental Videos All Versions of this Article: blood-2006-04-011551v1 108/6/1903    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 Ruggeri, Z. M. Articles by Reininger, A. J. Search for Related Content PubMed PubMed Citation Articles by Ruggeri, Z. M. Articles by Reininger, A. J. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Activation-independent platelet adhesion and aggregation under elevated shear stress Zaverio M. Ruggeri, Jennifer N. Orje, Rolf Habermann, Augusto B. Federici, and Armin J. Reininger From the Roon Centre for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA. Platelet aggregation, which contributes to bleeding arrest and also to thrombovascular disorders, is thought to initiate after signaling-induced activation. We found that this paradigm does not apply under blood flow conditions comparable to those existing in stenotic coronary arteries. Platelets interacting with immobilized von Willebrand factor (VWF) aggregate independently of activation when soluble VWF is present and the shear rate exceeds 10 000 s–1 (shear stress = 400 dyn/cm2). Above this threshold, active A1 domains become exposed in soluble VWF multimers and can bind to glycoprotein Ib, promoting additional platelet recruitment. Aggregates thus formed are unstable until the shear rate approaches 20 000 s–1 (shear stress = 800 dyn/cm.2). Above this threshold, adherent platelets at the interface of surface-immobilized and membrane-bound VWF are stretched into elongated structures and become the core of aggregates that can persist on the surface for minutes. When isolated dimeric A1 domain is present instead of native VWF multimers, activation-independent platelet aggregation occurs without requiring shear stress above a threshold level, but aggregates never become firmly attached to the surface and progressively disaggregate as shear rate exceeds 6000 s–1. Platelet and VWF modulation by hydrodynamic force is a mechanism for activation-independent aggregation that may support thrombotic arterial occlusion. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Maugeri, P. Rovere-Querini, V. Evangelista, C. Covino, A. Capobianco, M. T. S. Bertilaccio, A. Piccoli, L. Totani, D. Cianflone, A. Maseri, et al. Neutrophils phagocytose activated platelets in vivo: a phosphatidylserine, P-selectin, and {beta}2 integrin-dependent cell clearance program Blood, May 21, 2009; 113(21): 5254 - 5265. [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] A. K. Chauhan, J. Kisucka, A. Brill, M. T. Walsh, F. Scheiflinger, and D. D. 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