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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 (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 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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 18, 2006 Accepted September 30, 2006 Correlation between antiphospholipid antibodies that recognize domain I of 2-glycoprotein I and a reduction in the anticoagulant activity of annexin A5 Bas de Laat, Xiao-Xuan Wu, Menno van Lummel, Ronald H.W.M. Derksen, Philip G. de Groot*, and Jacob H. Rand University Medical Center Utrecht, Netherlands Montefiore Medical Center, Albert Einstein College of Medicine * Corresponding author; email: ph.g.degroot{at}umcutrecht.nl. 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-2-glycoprotein I (2GPI) antibodies recognize domain I and cause LAC. The (American) authors reported that aPL disrupt an anticoagulant annexin A5 (AnxA5) crystal shield. We investigated whether anti-domain I antibodies correlate with disruption of AnxA5-anticoagulant activity. We studied a well-characterized group of 33 patients including subgroups with 2GPI-dependent LAC that recognize domain I (n=11), 2GPI-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 2GPI-dependent LAC (Group A, all with thrombosis) had significantly lower AnxA5-anticoagulant ratios than those with 2GPI-independent LAC (Group B, thrombosis n=4)(157.8% vs 235.6%, p<0.001) and those without LAC (Group C, thrombosis n=2) (157.8% vs 232.5%, p<0.001). There was no difference in the ratios between group B and C (P=0.92). Plasmas with 2GPI-dependent LAC that recognize domain I displayed significantly increased AnxA5 resistance, suggesting that specifically anti-2GPI 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? This article has been cited by other articles: A Tincani, M Filippini, M Scarsi, M Galli, and P. Meroni European attempts for the standardisation of the antiphospholipid antibodies Lupus, September 1, 2009; 18(10): 913 - 919. [Abstract] [PDF] P. Meroni, A Tincani, M. Alarcon-Riquelme, Y Shoenfeld, and M. Borghi European Forum on Antiphospholipid Antibodies: research in progress Lupus, September 1, 2009; 18(10): 924 - 929. [Abstract] [PDF] J. Rand, X. Wu, A. Quinn, and D. Taatjes Resistance to annexin A5 anticoagulant activity: a thrombogenic mechanism for the antiphospholipid syndrome Lupus, October 1, 2008; 17(10): 922 - 930. [Abstract] [PDF]

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