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Blood, 1 November 2004, Vol. 104, No. 9, pp. 2783-2790. Prepublished online as a Blood First Edition Paper on July 8, 2004; DOI 10.1182/blood-2004-01-0203. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-01-0203v1 104/9/2783    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 Rand, J. H. Articles by Ortel, T. L. Search for Related Content PubMed PubMed Citation Articles by Rand, J. H. Articles by Ortel, T. L. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology 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 Detection of antibody-mediated reduction of annexin A5 anticoagulant activity in plasmas of patients with the antiphospholipid syndrome Jacob H. Rand, Xiao-Xuan Wu, Robert Lapinski, Waander L. van Heerde, Chris P. Reutelingsperger, Pojen P. Chen, and Thomas L. Ortel From the Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; the Department of Community and Preventive Medicine, Mount Sinai School of Medicine, New York, NY; the Central Hematology Laboratory, University Medical Center St Radboud, Nijmegen, the Netherlands; the Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; the Division of Rheumatology, University of California at Los Angeles, Los Angeles, CA; and the Departments of Medicine and Pathology, Duke University Medical Center, Durham, NC. Annexin A5 (A5) forms 2-dimensional crystals over phospholipid bilayers, blocking their availability for coagulation reactions. Recently, human antiphospholipid (aPL) monoclonal antibodies (mAbs) have been demonstrated by atomic force microscopy (AFM) to disrupt this crystallization and accelerate coagulation. We therefore performed a study with small, well-defined groups of patients to investigate whether these effects on A5 binding and activity are also detectable in plasmas from patients with the aPL syndrome. A5 binding to phospholipid was significantly reduced by plasmas of patients with the aPL syndrome and thromboembolism compared with healthy controls (mean ± SD, 26.7 ± 4.3 ng/well [n = 25] vs 30.5 ± 3.1 ng/well [n = 20], P < .01) and the non-aPL thromboembolism group (29.9 ± 3.2 ng/well [n = 15], P < .05). A5 anticoagulant activity was reduced by plasmas of patients with aPL syndrome and thromboembolism compared with aPL antibodies without thrombosis (182 ± 31% [n = 25] vs 210 ± 35% [n = 26], P < .01), non-aPL thromboembolism (229 ± 16% [n = 15], P < .001), and healthy controls (231 ± 14% [n = 30], P < .001). In conclusion, in accordance with recent AFM data with monoclonal human aPL antibodies, plasmas from patients with aPL antibodies with thromboembolism reduce both A5 binding to phospholipid and A5 anticoagulant activity. This "annexin A5 resistance" identifies a novel mechanism for thrombosis in the aPL syndrome. (Blood. 2004;104: 2783-2790) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Antiphospholipid antibodies: a mosaic of pathogenic effects? Silvia S. Pierangeli Blood 2004 104: 2619-2620. [Full Text] [PDF] This article has been cited by other articles: B. de Laat, X.-X. Wu, M. van Lummel, R. H. W. M. Derksen, P. G. de Groot, and J. H. Rand Correlation between antiphospholipid antibodies that recognize domain I of {beta}2-glycoprotein I and a reduction in the anticoagulant activity of annexin A5 Blood, February 15, 2007; 109(4): 1490 - 1494. [Abstract] [Full Text] [PDF] B. Giannakopoulos, F. Passam, S. Rahgozar, and S. A. Krilis Current concepts on the pathogenesis of the antiphospholipid syndrome Blood, January 15, 2007; 109(2): 422 - 430. [Abstract] [Full Text] [PDF] X. Huang, W.-Q. Ding, J. L. Vaught, R. F. Wolf, J. H. Morrissey, R. G. Harrison, and S. E. Lind A soluble tissue factor-annexin V chimeric protein has both procoagulant and anticoagulant properties Blood, February 1, 2006; 107(3): 980 - 986. [Abstract] [Full Text] [PDF]

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