LOW-MOLECULAR-WEIGHT HEPARIN (FRAGMIN) AND THROMBIN ACTIVE-SITE INHIBITOR (ARGATROBAN) COMPARED IN EXPERIMENTAL ARTERIAL AND VENOUS THROMBOSIS AND BLEEDING-TIME

The antithrombotic and bleeding effects of a low-molecular-weight hepa rin (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. E ach drug was tested in multiple intravenous (i.v.) doses and inhibited venous and arterial thrombosis when the activated partial thromboplas tin time (APTT) was increased as much as or more than twofold, althoug h greater APTT increases were required with fragmin and against arteri al thrombosis, Fragmin and argatroban decreased to an equivalent exten t the weight of venous thrombi induced by stasis (greater than or equa l to 99%) or vessel injury (90 and 96%, respectively). The maximum inh ibition of arterial thrombosis was less with fragmin (69%) and argatro ban (65%) and required higher doses of each drug relative to venous th rombosis. At doses that were just optimal against arterial thrombosis, bleeding time was increased moderately by fragmin (32%) and was unaff ected by argatroban. These studies demonstrate that closes of fragmin and argatroban that exert comparable antithrombotic activity in large arteries and veins have only moderate effects on bleeding time in smal l arteries.