SEARCH:   Advanced

Blood, 15 January 2007, Vol. 109, No. 2, pp. 394. This Article Full Text (PDF) 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 Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Furie, B. Search for Related Content PubMed Articles by Furie, B. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS Comment on Maxwell et al, page 566 Platelets: tetherballs in thrombus formation Bruce Furie HARVARD MEDICAL SCHOOL Although every student of hematology learns that platelets first adhere to the injured vessel wall, change shape, get activated, then aggregate to form the platelet plug, it is just not quite that simple. In the current issue, Maxwell and colleagues show that thrombus formation in vivo involves a 2-step process for platelet aggregation, and this process is distinct from the events that characterize thrombus formation either under low shear (0-1000 s–1) or at very high shear (> 10 000 s–1). But what happens at physiologic shear, between 1000 and 10 000 s–1? In these studies in the microcirculation of a live rat, thrombus formation is initiated by photoactivation of rose bengal dye to injure the vessel wall through an oxidative process. This is one of a number of nonphysiologic thrombosis models that are widely used in animal models of thrombosis. Unstimulated platelets circulate in the blood as discoid structures. In the current work, these discoid platelets in the circulation come in contact with discoid platelets immobilized on the vessel wall, and the differential interference contrast (DIC) microscopy images of this process are striking. Circulating platelets become associated with thrombus-bound platelets, with the moving platelet sliding along the immobilized platelet to maximize cell-cell contact. The first phase of platelet aggregation that occurs at physiologic shear rates in the arterial circulation involves shear-induced formation of membrane tethers between platelets. The higher the shear rate, the more tethers that are observed, and the larger the (reversible) platelet aggregates. The platelets, in their discoid shape, become linked side to side through these tethers. At these shear rates, these tethers require the interaction of both platelet GPIb with matrix von Willebrand factor and the integrin IIbß3 with matrix fibrinogen. In addition, the platelets must be activated and engage the adhesive function of both of the platelet receptors GPIb and IIbß3. During the second phase, platelets undergo their characteristic shape change and demonstrate irreversible platelet adhesion. The release of ADP is critical to the recruitment of additional platelets into the developing thrombus. The dynamics of platelet aggregation and thus thrombus growth are greatly influenced by 3 factors: (1) high shear stress, which leads to increased number of tethers and tighter binding; (2) the number of platelets and thus the platelet surface density; and (3) matrix reactivity, with the availability of certain adhesive proteins, GPIb and IIbß3, that are counterreceptors of other adhesion molecules. Thrombosis remains the leading cause of death in Western society. Given the importance of this pathologic process, understanding its molecular and cellular details in a living animal has implications for the identification of appropriate targets and for therapeutic design. Footnotes Conflict-of-interest disclosure: The author declares no competing financial interests. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Identification of a 2-stage platelet aggregation process mediating shear-dependent thrombus formation Mhairi J. Maxwell, Erik Westein, Warwick S. Nesbitt, Simon Giuliano, Sacha M. Dopheide, and Shaun P. Jackson Blood 2007 109: 566-576. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) 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 Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Furie, B. Search for Related Content PubMed Articles by Furie, B. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

	Blood Online is supported in part by Genentech BioOncology and Biogen Idec
	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020