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Blood, 1 December 2005, Vol. 106, No. 12, pp. 3791-3796. Prepublished online as a Blood First Edition Paper on August 18, 2005; DOI 10.1182/blood-2005-05-1938. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-05-1938v1 106/12/3791    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 Warkentin, T. E. Articles by Kelton, J. G. Search for Related Content PubMed PubMed Citation Articles by Warkentin, T. E. Articles by Kelton, J. G. Related Collections Hemostasis, Thrombosis, and Vascular Biology Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS Anti–platelet factor 4/heparin antibodies in orthopedic surgery patients receiving antithrombotic prophylaxis with fondaparinux or enoxaparin Theodore E. Warkentin, Richard J. Cook, Victor J. Marder, Jo-Ann I. Sheppard, Jane C. Moore, Bengt I. Eriksson, Andreas Greinacher, and John G. Kelton From the Department of Pathology and Molecular Medicine and Department of Medicine, McMaster University, Hamilton, ON, Canada; Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, ON, Canada; Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA; Department of Orthopedics, Surgical Sciences, Göteborg University, Göteborg, Sweden; and Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany. Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating IgG antibodies that recognize platelet factor 4 (PF4) bound to heparin. Immunogenicity of heparins differs in that unfractionated heparin (UFH) induces more anti–PF4/heparin antibodies than low-molecular-weight heparin (LMWH) and UFH also causes more HIT. Fondaparinux, a synthetic anticoagulant modeled after the antithrombin-binding pentasaccharide, is believed to be nonimmunogenic. We tested 2726 patients for anti–PF4/heparin antibodies after they were randomized to receive antithrombotic prophylaxis with fondaparinux or LMWH (enoxaparin) following hip or knee surgery. We also evaluated in vitro cross-reactivity of the IgG antibodies generated against PF4 in the presence of UFH, LMWH, danaparoid, or fondaparinux. We found that anti–PF4/heparin antibodies were generated at similar frequencies in patients treated with fondaparinux or enoxaparin. Although antibodies reacted equally well in vitro against PF4/UFH and PF4/LMWH, and sometimes weakly against PF4/danaparoid, none reacted against PF4/fondaparinux, including even those sera obtained from patients who formed antibodies during fondaparinux treatment. At high concentrations, however, fondaparinux inhibited binding of HIT antibodies to PF4/polysaccharide, indicating that PF4/fondaparinux interactions occur. No patient developed HIT. We conclude that despite similar immunogenicity of fondaparinux and LMWH, PF4/fondaparinux, but not PF4/LMWH, is recognized poorly by the antibodies generated, suggesting that the risk of HIT with fondaparinux likely is very low. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: The immune paradox of fondaparinux Gowthami M. Arepally Blood 2005 106: 3686-3687. [Full Text] [PDF] This article has been cited by other articles: T. E. Warkentin, A. Greinacher, A. Koster, and A. M. Lincoff Treatment and Prevention of Heparin-Induced Thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 340S - 380S. [Abstract] [Full Text] [PDF] S. Suvarna, B. Espinasse, R. Qi, R. Lubica, M. Poncz, D. B. Cines, M. R. Wiesner, and G. M. Arepally Determinants of PF4/heparin immunogenicity Blood, December 15, 2007; 110(13): 4253 - 4260. [Abstract] [Full Text] [PDF] J. Hirsh, M. O'Donnell, and J. W. Eikelboom Beyond Unfractionated Heparin and Warfarin: Current and Future Advances Circulation, July 31, 2007; 116(5): 552 - 560. [Full Text] [PDF] T. E. Warkentin, B. T. Maurer, R. H. Aster, J. Soffer, J. Patel, and R. Saltzman Heparin-Induced Thrombocytopenia Associated with Fondaparinux N. Engl. J. Med., June 21, 2007; 356(25): 2653 - 2655. [Full Text] [PDF] K. R. McCrae, D. C. Matthews, and M. Linenberger Consultative hematology ASH Self-Assessment Program, January 1, 2007; 2007(1): 466 - 505. [Full Text] [PDF] A. Greinacher, M. Gopinadhan, J.-U. Gunther, M. A. Omer-Adam, U. Strobel, T. E. Warkentin, G. Papastavrou, W. Weitschies, and C. A. Helm Close Approximation of Two Platelet Factor 4 Tetramers by Charge Neutralization Forms the Antigens Recognized by HIT Antibodies Arterioscler. Thromb. Vasc. Biol., October 1, 2006; 26(10): 2386 - 2393. [Abstract] [Full Text] [PDF] T. E. Warkentin Think of HIT When Thrombosis Follows Heparin. Chest, September 1, 2006; 130(3): 631 - 632. [Full Text] [PDF] L. Mazzolai, P. Hohlfeld, F. Spertini, D. Hayoz, M. Schapira, and M. A. Duchosal Fondaparinux is a safe alternative in case of heparin intolerance during pregnancy Blood, September 1, 2006; 108(5): 1569 - 1570. [Abstract] [Full Text] [PDF] G. M. Arepally and T. L. Ortel Heparin-Induced Thrombocytopenia N. Engl. J. Med., August 24, 2006; 355(8): 809 - 817. [Full Text] [PDF] T. E. Warkentin Think of HIT Hematology, January 1, 2006; 2006(1): 408 - 414. [Abstract] [Full Text] [PDF]

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