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Article Dans Une Revue Journal of Biomedical Materials Research Part A Année : 2007

Effects on coagulation of a synthetic heparan mimetic given intraperitoneally or orally.

Résumé

OTR4120, which belongs to a family of heparan sulfate-mimetic polymers, promotes tissue repair when injected locally in doses of a few micrograms. As OTR4120 is a sulfated polysaccharide, we investigated its possible role on the coagulation cascade. We used both in vitro and in vivo assays. Increases in clotting times (thrombin time, prothrombin time, and activated partial thromboplastin time) occurred with OTR4120 in doses at least 10 times lower than heparin. OTR4120 dose-dependently inhibited the biological activity of thrombin and bound thrombin with an affinity of 14 +/- 2 nM. SDS-PAGE showed that OTR4120 induced the formation of covalently linked complexes between antithrombin III or heparin cofactor II and thrombin. OTR4120 induced anticoagulant effects, and antithrombin activity was greatest 90 min after intraperitoneal injection. No bleeding or significant platelet count changes occurred with doses smaller than 55 mg/kg. Interestingly, orally administered OTR4120 crossed the gastrointestinal barrier and, in a dose of 70 mg/kg, induced significant ex vivo antithrombotic activity in the bloodstream. (c) 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007.

Dates et versions

hal-00172752 , version 1 (17-09-2007)

Identifiants

Citer

Said Charef, Emmanuel Petit, Denis Barritault, José Courty, Jean-Pierre Caruelle. Effects on coagulation of a synthetic heparan mimetic given intraperitoneally or orally.. Journal of Biomedical Materials Research Part A, 2007, epub ahead of print. ⟨10.1002/jbm.a.31385⟩. ⟨hal-00172752⟩

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