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 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.
Savi
Pierre
P
Cardiovascular/Thrombosis Research Department, Sanofi-Synthelabo Recherche, Toulouse, France. pierre.savi@sanofi-synthelabo.com
Chong
Beng H
BH
Greinacher
Andreas
A
Gruel
Yves
Y
Kelton
John G
JG
Warkentin
Theodore E
TE
Eichler
Petra
P
Meuleman
Dick
D
Petitou
Maurice
M
Herault
Jean-Pascal
JP
Cariou
Roger
R
Herbert
Jean-Marc
JM
D001323:Autoantibodies / Q000276:immunology*; D005434:Flow Cytometry; D000077425:Fondaparinux; D006493:Heparin / Q000276:immunology* / Q000494:pharmacology*; D006801:Humans; D015539:Platelet Activation / Q000187:drug effects*; D011134:Polysaccharides / Q000494:pharmacology*; D012701:Serotonin / Q000097:blood; D016037:Single-Blind Method; D013922:Thrombocytosis / Q000097:blood / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy
D001323:Autoantibodies; D011134:Polysaccharides; D012701:Serotonin; D006493:Heparin; D000077425:Fondaparinux