Effect of fondaparinux on platelet activation in the presence of heparin-dependent antibodies: a blinded comparative multicenter study with unfractionated heparin

Heparin-induced thrombocytopenia (HIT) is a complication of heparin therapy caused by antibodies against a complex of platelet factor 4 and heparin. Fondaparinux (Arixtra) is a new synthetic selective factor Xa inhibitor. We performed a serologic study to determine the cross-reactivity of HIT sera w...

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Bibliographic Details
Published in:Blood 2005-01, Vol.105 (1), p.139-144
Main Authors: Savi, Pierre, Chong, Beng H., Greinacher, Andreas, Gruel, Yves, Kelton, John G., Warkentin, Theodore E., Eichler, Petra, Meuleman, Dick, Petitou, Maurice, Herault, Jean-Pascal, Cariou, Roger, Herbert, Jean-Marc
Format: Article
Language:English
Subjects:
Autoantibodies - immunology
Biological and medical sciences
Flow Cytometry
Fondaparinux
Hematologic and hematopoietic diseases
Heparin - immunology
Heparin - pharmacology
Humans
Medical sciences
Platelet Activation - drug effects
Platelet diseases and coagulopathies
Polysaccharides - pharmacology
Serotonin - blood
Single-Blind Method
Thrombocytosis - blood
Thrombocytosis - chemically induced
Thrombocytosis - complications
Thrombocytosis - drug therapy
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Summary:Heparin-induced thrombocytopenia (HIT) is a complication of heparin therapy caused by antibodies against a complex of platelet factor 4 and heparin. Fondaparinux (Arixtra) is a new synthetic selective factor Xa inhibitor. We performed a serologic study to determine the cross-reactivity of HIT sera with fondaparinux. Using a prospective, blinded study design, 39 clinically and serologically confirmed sera from patients with HIT and 15 control sera were sent to 3 different laboratories, each of which specialized in a particular HIT assay. These include the serotonin release assay, heparin-induced platelet agglutination assay, and platelet aggregation assay. Two of 82 assays (2.4%) performed in the presence of control sera were positive, both with unfractionated heparin. In the presence of HIT sera, 75 of 94 (79.8%) evaluable assays were positive with unfractionated heparin; fondaparinux was significantly (P < .001) less reactive than unfractionated heparin, only 3 of 91 evaluable assays (3.3%) being positive. Using flow cytometry, unlike unfractionated heparin, fondaparinux did not induce the binding of PAC1 and anti-CD62 monoclonal antibodies or of annexin V to platelets with HIT sera. Together, these results suggest that fondaparinux is nonreactive to HIT sera and raise the possibility that the drug may be used for prophylaxis and treatment of thrombosis in patients with a history of HIT.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2004-05-2010