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Blood, 1 January 2005, Vol. 105, No. 1, pp. 139-144.
Prepublished online as a Blood First Edition Paper on September 23, 2004; DOI 10.1182/blood-2004-05-2010.


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Submitted June 2, 2004
Accepted August 12, 2004

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

Pierre Savi*, Beng H Chong, Andreas Greinacher, Yves Gruel, John G Kelton, Theodore E Warkentin, Petra Eichler, Dick Meuleman, Maurice Petitou, Jean-Pascal Herault, Roger Cariou, and Jean-Marc Herbert

Sanofi~Synthelabo Recherche, Toulouse, France
Department of Medicine, St George Hospital, Kogarah, Australia
Department of Immunology and Transfusion Medicine, Ernst-Moritz-Arndt-University, Greifswald, Germany
Service d'Hematologie-Hemostase, Hopital Trousseau, Tours, France
Platelet Immunology Laboratory, McMaster University, Hamilton, Ontario, Canada
NV Organon, Oss, The Netherlands

* Corresponding author; email: pierre.savi{at}sanofi-synthelabo.com.

Heparin-induced thrombocytopenia (HIT) is a complication of heparin therapy caused by antibodies against a complex of platelet factor 4 and heparin. Fondaparinux is a new synthetic selective factor Xa inhibitor. We performed a serological 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 three 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<0.001) less reactive than unfractionated heparin, only three of 91 evaluable assays (3.3%) being positive. Using flow cytometry, unlike unfractionated heparin, fondaparinux did not induce the binding of PAC-1 and anti-CD62 monoclonal antibodies or of annexin V to platelets with HIT sera. Together, this study suggests that fondaparinux is non-reactive to HIT sera and raises the possibility that it may be used for prophylaxis and treatment of thrombosis in patients with a history of HIT.


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