Abstract
Semuloparin (S) (Sanofi‐Aventis, Paris, France) is an ULMWH exhibiting high anti‐Xa (aXa) activity due to preservation of antithrombin‐binding sites. Antithrombotic (jugular vein clamping model) and hemorrhagic (tail transection model) effects of S, the LWMH enoxaparin (E) and heparin (H) were compared in Sprague‐Dawley rats treated subcutaneously (SC) with doses of 1.0 and 2.5 mg/kg (n=5). Blood samples collected prior to euthanasia were analyzed using aPTT, aXa and Heptest (HT) assays. 1.0 mg/kg SC H significantly prolonged bleeding time compared to control (C). All agents had equivalent antithrombotic effects. S and E significantly increased HT prolongation and aXa activity compared to C and H (HT: p<0.001 A vs H; p<0.05 E vs H; Xa: p<0.001 A vs H; p<0.01 E vs H). At 2.5 mg/kg SC, only S did not significantly prolong bleeding time compared to C. Only H significantly increased aPTT compared to C. Prolongation of HT and aXa activity was observed with all agents. S exhibited a more potent aXa activity than H (p<0.001 S vs H). All agents demonstrated a dose‐dependent antithrombotic effect. Bleeding time was lower with S at both dosages, suggesting a better safety profile. AXa activity with S was closely related to its antithrombotic activity. These studies suggest that S represents a new alternative for the prevention of thrombotic disorders with an improved bene&#64257;t/risk pro&#64257;le compared with standard H and E.
Published Version
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