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Blood, 15 January 2007, Vol. 109, No. 2, pp. 566-576. Prepublished online as a Blood First Edition Paper on September 21, 2006; DOI 10.1182/blood-2006-07-028282. This Article Full Text Full Text (PDF) Supplemental Methods and Videos All Versions of this Article: blood-2006-07-028282v1 109/2/566    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 Maxwell, M. J. Articles by Jackson, S. P. Search for Related Content PubMed PubMed Citation Articles by Maxwell, M. J. Articles by Jackson, S. P. 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 Identification of a 2-stage platelet aggregation process mediating shear-dependent thrombus formation Mhairi J. Maxwell1, Erik Westein1, Warwick S. Nesbitt1, Simon Giuliano1, Sacha M. Dopheide1, and Shaun P. Jackson1, 1 Australian Centre for Blood Diseases, Monash University, Prahran, Australia Disturbances of blood flow at sites of atherosclerotic plaque rupture are one of the key pathogenic events promoting platelet activation and arterial thrombus formation. Shear effects of platelets have been extensively investigated in vitro; however, the mechanisms by which shear promotes platelet aggregation in vivo remain incompletely understood. By employing high-resolution imaging techniques to in vitro and in vivo thrombosis models, we demonstrate a unique mechanism initiating shear-dependent platelet aggregation involving aggregate formation between discoid platelets. These discoid platelet aggregates are initially unstable and result from the development of membrane tethers between coadhering platelets. Tether formation involves the adhesive function of GPIb/V/IX and integrin IIbß3, and conversion of discoid platelet aggregates into stable aggregates requires released ADP. The efficiency of this process is regulated by 3 independent variables, including the reactivity of the adhesive substrate, the level of shear flow, and the platelet density at the adhesive surface. These studies identify a new mechanism initiating platelet aggregation that is critically influenced by shear, physical proximity between translocating platelets, and membrane tether formation. Moreover, they provide a model to explain how the discoid morphology of platelets facilitates the maintenance of adhesive interactions with thrombogenic surfaces under high shear stress conditions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Platelets: tetherballs in thrombus formation Bruce Furie Blood 2007 109: 394. [Full Text] [PDF] This article has been cited by other articles: A. Ono, E. Westein, S. Hsiao, W. S. Nesbitt, J. R. Hamilton, S. M. Schoenwaelder, and S. P. Jackson Identification of a fibrin-independent platelet contractile mechanism regulating primary hemostasis and thrombus growth Blood, July 1, 2008; 112(1): 90 - 99. [Abstract] [Full Text] [PDF] Z. Touat, L. Lepage, V. Ollivier, P. Nataf, U. Hvass, J. Labreuche, M. Jandrot-Perrus, J.-B. Michel, and G. Jondeau Dilation-Dependent Activation of Platelets and Prothrombin in Human Thoracic Ascending Aortic Aneurysm Arterioscler Thromb Vasc Biol, May 1, 2008; 28(5): 940 - 946. [Abstract] [Full Text] [PDF] M. C. Berndt and R. K. Andrews New Direction for WE Thrombin Arterioscler Thromb Vasc Biol, February 1, 2008; 28(2): 205 - 207. [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. M. Schoenwaelder, A. Ono, S. Sturgeon, S. M. Chan, P. Mangin, M. J. Maxwell, S. Turnbull, M. Mulchandani, K. Anderson, G. Kauffenstein, et al. Identification of a Unique Co-operative Phosphoinositide 3-Kinase Signaling Mechanism Regulating Integrin {alpha}IIbbeta3 Adhesive Function in Platelets J. Biol. Chem., September 28, 2007; 282(39): 28648 - 28658. [Abstract] [Full Text] [PDF] R. K. Andrews, D. Karunakaran, E. E. Gardiner, and M. C. Berndt Platelet Receptor Proteolysis: A Mechanism for Downregulating Platelet Reactivity Arterioscler Thromb Vasc Biol, July 1, 2007; 27(7): 1511 - 1520. [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]

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