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Blood, 15 January 2004, Vol. 103, No. 2, pp. 594-600. Prepublished online as a Blood First Edition Paper on September 11, 2003; DOI 10.1182/blood-2003-05-1385. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-05-1385v1 103/2/594    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 Leon, C. Articles by Engelmann, B. Search for Related Content PubMed PubMed Citation Articles by Leon, C. Articles by Engelmann, B. Related Collections Hemostasis, Thrombosis, and Vascular Biology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Platelet ADP receptors contribute to the initiation of intravascular coagulation Catherine Leon, Meike Alex, Antje Klocke, Eberhard Morgenstern, Christine Moosbauer, Anita Eckly, Michael Spannagl, Christian Gachet, and Bernd Engelmann From Vaskuläre Biologie und Hämostase, Institut für Klinische Chemie, Ludwig-Maximilians-Universität München, Germany; Institut National de la Sante et de la Recherche Medicale U311, Etablissement Francais du Sang-Alsace, Strasbourg, France; Medizinische Biologie, Universität des Saarlandes, Homburg, Germany; and Hämostaseologie und Transfusionsmedizin, Ludwig-Maximilians-Universität München, Germany. While the adenosine 5'-diphosphate (ADP) pathway is known to enhance thrombus formation by recruiting platelets and leukocytes to the primary layer of collagen-adhering platelets, its role for the initiation of coagulation has not been revealed. Ex vivo inhibition of the P2Y12 ADP receptor by clopidogrel administration diminished the rapid exposure of tissue factor (TF), the major initiator of coagulation, in conjugates of platelets with leukocytes established by the contact of whole blood with fibrillar collagen. Under in vitro conditions, the P2Y12 and P2Y1 ADP receptors were both found to be implicated in the exposure of TF in collagen-activated whole blood. Immunoelectron-microscopy revealed that collagen elicited the release of TF from its storage pools within the platelets. Functional activation of the intravascular TF was reduced by inhibition of the ADP receptors, partially due to the disruption of the platelet-neutrophil adhesions. Injection of collagen into the venous system of mice increased the number of thrombin-antithrombin complexes, indicative for the formation of thrombin in vivo. In P2Y1-deficient mice, the ability of collagen to enhance the generation of thrombin was impaired. In conclusion, the platelet ADP pathway supports the initiation of intravascular coagulation, which is likely to contribute to the concomitant formation of fibrin at the site of the growing thrombus. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. O. Maree and D. J. Fitzgerald Variable Platelet Response to Aspirin and Clopidogrel in Atherothrombotic Disease Circulation, April 24, 2007; 115(16): 2196 - 2207. [Full Text] [PDF] C. Moosbauer, E. Morgenstern, S. L. Cuvelier, D. Manukyan, K. Bidzhekov, S. Albrecht, P. Lohse, K. D. Patel, and B. 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