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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1490-1494. Prepublished online as a Blood First Edition Paper on October 19, 2006; DOI 10.1182/blood-2006-07-030148. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-07-030148v1 109/4/1490    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by de Laat, B. Articles by Rand, J. H. Search for Related Content PubMed PubMed Citation Articles by de Laat, B. Articles by Rand, J. H. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Correlation between antiphospholipid antibodies that recognize domain I of ß2-glycoprotein I and a reduction in the anticoagulant activity of annexin A5 Bas de Laat1, Xiao-Xuan Wu2, Menno van Lummel1, Ronald H. W. M. Derksen3, Philip G. de Groot1, and Jacob H. Rand2 1 Department of Haematology, University Medical Center Utrecht, The Netherlands; 2 Pathology Department, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; 3 Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, The Netherlands The paradoxical correlation between thrombosis and the lupus anticoagulant (LAC) effect is an enigmatic feature of the antiphospholipid (aPL) syndrome. The Dutch authors previously reported that thrombosis-related anti–ß2-glycoprotein I (ß2GPI) antibodies recognize domain I and cause LAC. The American authors reported that aPLs disrupt an anticoagulant annexin A5 (AnxA5) crystal shield. We investigated whether antidomain I antibodies correlate with disruption of AnxA5-anticoagulant activity. We studied a well-characterized group of 33 patients including subgroups with ß2GPI-dependent LAC that recognize domain I (n = 11), with ß2GPI-independent LAC (n = 12), and lacking LAC (n = 10). The effects on AnxA5-anticoagulant activity were determined with an AnxA5 resistance assay that measures coagulation times with and without AnxA5. Patients with ß2GPI-dependent LAC (group A, all with thrombosis) had significantly lower AnxA5-anticoagulant ratios than those with ß2GPI-independent LAC (group B, thrombosis n = 4; 157.8% versus 235.6%, P < .001) and those without LAC (group C, thrombosis n = 2; 157.8% versus 232.5%, P < .001). There was no difference in the ratios between groups B and C (P = .92). Plasmas with ß2GPI-dependent LAC that recognize domain I displayed significantly increased AnxA5 resistance, suggesting that specifically anti-ß2GPI antibodies compete with AnxA5 for anionic phospholipids. These results are consistent with a model in which aPL antibodies may promote thrombosis by interfering with the anticoagulant activity of AnxA5. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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