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Blood, 1 September 2007, Vol. 110, No. 5, pp. 1483-1491. Prepublished online as a Blood First Edition Paper on May 8, 2007; DOI 10.1182/blood-2006-10-053199. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-10-053199v1 110/5/1483    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 Hulstein, J. J. J. Articles by de Groot, P. G. Search for Related Content PubMed PubMed Citation Articles by Hulstein, J. J. J. Articles by de Groot, P. G. Related Collections Hemostasis, Thrombosis, and Vascular Biology Free Research Articles Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY ß2-Glycoprotein I inhibits von Willebrand factor–dependent platelet adhesion and aggregation Janine J. J. Hulstein1, Peter J. Lenting1, Bas de Laat1, Ron H. W. M. Derksen2, Rob Fijnheer1,3, and Philip G. de Groot1 1 Laboratory for Thrombosis and Haemostasis, Department of Clinical Chemistry and Haematology; 2 Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, Utrecht; 3 Jeroen Bosch Hospital, Department of Internal Medicine, Hertogenbosch, the Netherlands Patients with antiphospholipid syndrome are characterized by the association of thrombosis or pregnancy morbidity and the presence of antiphospholipid autoantibodies. Particularly, anti-ß2-glycoprotein (ß2 GPI) autoantibodies correlate with thrombosis, suggesting an antibody-induced gain of prothrombotic function and/or an antibody-induced loss of antithrombotic function of ß2 GPI. In the search for potential antithrombotic properties of ß2 GPI, we found that ß2 GPI inhibits von Willebrand factor (VWF)–induced platelet aggregation. In addition, platelet adhesion to a VWF-coated surface was decreased by 50% in the presence of ß2 GPI (P < .03). ß2 GPI binds to the A1 domain of VWF but preferably when the A1 domain is in its active glycoprotein Ib-binding conformation. Anti-ß2 GPI antibodies isolated from a subset of antiphospholipid syndrome patients neutralized the ß2 GPI-VWF interactions and thus the inhibitory activity of ß2 GPI. In comparison to healthy individuals, the amounts of active VWF in circulation were increased 1.5-fold (P < .001) in patients positive for lupus anticoagulant (LAC) due to anti-ß2 GPI antibodies. Thus, ß2 GPI is a biologically relevant inhibitor of VWF function by interfering with VWF-dependent platelet adhesion. Anti-ß2 GPI autoantibodies neutralize this inhibitory function and are associated with increased levels of active VWF. This mode of action could contribute to the thrombosis and consumptive thrombocytopenia observed in patients with anti-ß2 GPI antibodies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: ß2-GPI dampening of VWF-GPIb interaction Robert R. Montgomery Blood 2007 110: 1405. [Full Text] [PDF] This article has been cited by other articles: M. Lockshin and R. Derksen New developments in lupus-associated antiphospholipid syndrome Lupus, May 1, 2008; 17(5): 443 - 446. [Abstract] [PDF] Major Role for {beta}2-Glycoprotein-I in Coagulation Journal Watch Oncology and Hematology, September 11, 2007; 2007(911): 2 - 2. [Full Text]

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