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Anti-platelet factor 4/heparin antibodies in orthopedic surgery patients receiving antithrombotic prophylaxis with fondaparinux or enoxaparin
- Warkentin, T. E. (author)
- Cook, R. J. (author)
- Marder, V. J. (author)
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- Sheppard, J. A. (author)
- Moore, J. C. (author)
- Greinacher, A. (author)
- Kelton, J. G. (author)
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- (creator_code:org_t)
- 2005
- 2005
- English.
- In: Blood. - 0006-4971. ; 106:12, s. 3791-6
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kirurgi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Surgery (hsv//eng)
Keyword
- Anticoagulants/*immunology/therapeutic use
- Cross Reactions
- Double-Blind Method
- Enoxaparin/*therapeutic use
- Hip/surgery
- Humans
- Immunoenzyme Techniques
- Immunoglobulin G/blood
- Knee/surgery
- Orthopedic Procedures/adverse effects
- Platelet Factor 4/*immunology
- Polysaccharides/*immunology/therapeutic use
- Thrombocytopenia/chemically induced
- Venous Thrombosis/etiology/*prevention & control
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- ref (subject category)
- art (subject category)
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- Warkentin, T. E.
- Cook, R. J.
- Marder, V. J.
- Sheppard, J. A.
- Moore, J. C.
- Eriksson, Bengt ...
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- Greinacher, A.
- Kelton, J. G.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
- MEDICAL AND HEAL ...
- and Clinical Medicin ...
- and Surgery
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- Blood
- By the university
- University of Gothenburg
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