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Blood, 1 July 2008, Vol. 112, No. 1, pp. 90-99. Prepublished online as a Blood First Edition Paper on February 29, 2008; DOI 10.1182/blood-2007-12-127001. This Article Full Text (PDF) Supplemental Videos All Versions of this Article: blood-2007-12-127001v1 112/1/90    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 Ono, A. Articles by Jackson, S. P Search for Related Content PubMed PubMed Citation Articles by Ono, A. Articles by Jackson, S. P Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 3, 2007 Accepted February 19, 2008 Identification of a fibrin-independent platelet contractile mechanism regulating primary hemostasis and thrombus growth Akiko Ono, Erik Westein, Sarah Hsiao, Warwick S Nesbitt, Justin R Hamilton, Simone M Schoenwaelder, and Shaun P Jackson* Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia * Corresponding author; email: shaun.jackson{at}med.monash.edu.au. A fundamental property of platelets is their ability to transmit cytoskeletal contractile forces to extracellular matrices. Whilst the importance of the platelet contractile mechanism in regulating fibrin clot retraction is well established its role in regulating the primary hemostatic response, independent of blood coagulation, remains ill-defined. Real-time analysis of platelet adhesion and aggregation on a collagen substrate revealed a prominent contractile phase during thrombus development, associated with a 30-40% reduction in thrombus volume. Thrombus contraction developed independent of thrombin and fibrin and resulted in the tight packing of aggregated platelets. Inhibition of the platelet contractile mechanism, with the myosin IIa inhibitor blebbistatin, or through Rho kinase antagonism, markedly inhibited thrombus contraction, preventing the tight packing of aggregated platelets and undermining thrombus stability in vitro. Utilizing a new intravital hemostatic model, we demonstrate that the platelet contractile mechanism is critical for maintaining the integrity of the primary hemostatic plug, independent of thrombin and fibrin generation. These studies demonstrate an important role for the platelet contractile mechanism in regulating primary hemostasis and thrombus growth. Furthermore, they provide new insight into the underlying bleeding diathesis associated with platelet contractility defects. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Thrombus stability on the vessel wall Alan T. Nurden Blood 2008 112: 4-5. [Full Text] [PDF] This article has been cited by other articles: A. C. Calkin, B. G. Drew, A. Ono, S. J. Duffy, M. V. Gordon, S. M. Schoenwaelder, D. Sviridov, M. E. Cooper, B. A. Kingwell, and S. P. Jackson Reconstituted High-Density Lipoprotein Attenuates Platelet Function in Individuals With Type 2 Diabetes Mellitus by Promoting Cholesterol Efflux Circulation, November 24, 2009; 120(21): 2095 - 2104. [Abstract] [Full Text] [PDF] R. M. Stone How I treat patients with myelodysplastic syndromes Blood, June 18, 2009; 113(25): 6296 - 6303. [Full Text] [PDF]

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