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Blood, 23 July 2009, Vol. 114, No. 4, pp. 881-890. Prepublished online as a Blood First Edition Paper on April 16, 2009; DOI 10.1182/blood-2008-07-171066. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-07-171066v1 114/4/881    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 Google Scholar Articles by van der Meijden, P. E. J. Articles by Heemskerk, J. W. M. PubMed PubMed Citation Articles by van der Meijden, P. E. J. Articles by Heemskerk, J. W. M. Related Collections Thrombosis and Hemostasis Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  THROMBOSIS AND HEMOSTASIS Dual role of collagen in factor XII–dependent thrombus formation Paola E. J. van der Meijden1, Imke C. A. Munnix1, Jocelyn M. Auger2, José W. P. Govers-Riemslag1, Judith M. E. M. Cosemans1, Marijke J. E. Kuijpers1, Henri M. Spronk1, Steve P. Watson2, Thomas Renné3,4,*, and Johan W. M. Heemskerk1,* 1 Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, Maastricht, The Netherlands; 2 Centre for Cardiovascular Sciences Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom; 3 Institute of Clinical Biochemistry and Pathobiochemistry, University of Würzburg, Würzburg, Germany; and 4 Department of Molecular Medicine and Surgery, Karolinska University Hospital Solna, Karolinska, Sweden In vivo mouse models have indicated that the intrinsic coagulation pathway, initiated by factor XII, contributes to thrombus formation in response to major vascular damage. Here, we show that fibrillar type I collagen provoked a dose-dependent shortening of the clotting time of human plasma via activation of factor XII. This activation was mediated by factor XII binding to collagen. Factor XII activation also contributed to the stimulating effect of collagen on thrombin generation in plasma, and increased the effect of platelets via glycoprotein VI activation. Furthermore, in flow-dependent thrombus formation under coagulant conditions, collagen promoted the appearance of phosphatidylserine-exposing platelets and the formation of fibrin. Defective glycoprotein VI signaling (with platelets deficient in LAT or phospholipase C2) delayed and suppressed phosphatidylserine exposure and thrombus formation. Markedly, these processes were also suppressed by absence of factor XII or XI, whereas blocking of tissue factor/factor VIIa was of little effect. Together, these results point to a dual role of collagen in thrombus formation: stimulation of glycoprotein VI signaling via LAT and PLC2 to form procoagulant platelets; and activation of factor XII to stimulate thrombin generation and potentiate the formation of platelet-fibrin thrombi. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Thrombosis in flowing blood Alec A. Schmaier and Alvin H. Schmaier Blood 2009 114: 754-756. [Full Text] [PDF] This article has been cited by other articles: F. May, I. Hagedorn, I. Pleines, M. Bender, T. Vogtle, J. Eble, M. Elvers, and B. Nieswandt CLEC-2 is an essential platelet-activating receptor in hemostasis and thrombosis Blood, October 15, 2009; 114(16): 3464 - 3472. [Abstract] [Full Text] [PDF] A. A. Schmaier and A. H. Schmaier Thrombosis in flowing blood Blood, July 23, 2009; 114(4): 754 - 756. [Full Text] [PDF]

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