Low-Molecular-Weight Heparin (Fragmin) and Thrombin Active-Site Inhibitor (Argatroban) Compared in Experimental Arterial and Venous Thrombosis and Bleeding Time

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Abstract
The antithrombotic and bleeding effects of a low-molecular-weight heparin (LMWH, fragmin) and a thrombin active-site inhibitor (argatroban) were determined in anesthetized rats. Occlusive thrombi were produced in the vena cava, either by partial stasis of blood flow or transmural vessel injury, and in the carotid artery by transmural vessel injury. Bleeding time was measured by puncturing small mesenteric arteries. Each drug was tested in multiple intravenous (i.v.) doses and inhibited venous and arterial thrombosis when the activated partial thromboplastin time (APTT) was increased as much as or more than twofold, although greater APTT increases were required with fragmin and against arterial thrombosis. Fragmin and argatroban decreased to an equivalent extent the weight of venous thrombi induced by stasis (> or = 99%) or vessel injury (90 and 96%, respectively). The maximum inhibition of arterial thrombosis was less with fragmin (69%) and argatroban (65%) and required higher doses of each drug relative to venous thrombosis. At doses that were just optimal against arterial thrombosis, bleeding time was increased moderately by fragmin (32%) and was unaffected by argatroban. These studies demonstrate that doses of fragmin and argatroban that exert comparable antithrombotic activity in large arteries and veins have only moderate effects on bleeding time in small arteries.

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