446 Antithrombotic and thrombolytic activity of heparins in a rat model of laser induced thrombosis

Abstract

The mode of action by which heparins exert their antithrombotic effect is not fully understood. Antithrombotic action persists much longer than the inhibition of even sensitive coagulation parameters. We therefore have investigated antithrombotic and thrombolytic activity of two low molecular weight heparins Fraxiparin (Sanofi) and Clexane (Rhone-Poulenc) in a rat model of laser-induced thrombosis. The antithrombotic effect was measured by the number of laser injuries required to induce a defined venous thrombus which was at least as broad and as high as the vessel diameter. Thrombolytic activity of low molecular weight heparins was investigated by measuring the time from venous occlusion to recanalisation of the vessel. Fraxiparin in minimal dose of 0.001 mg/kg after iv injection showed antithrombotic effect in the laser thrombosis model. After single iv injection of this dose antithrombotic effect of Fraxiparin lasted longer than 6 h but less than 8 h. In higher dose of 0.01 mg/kg after single iv injection thrombolytic activity of Fraxiparin was observed. Also Clexane showed dose dependent antithrombotic and thrombolytic activity in this model. In dose of 0.005 mg/kg after single iv injection of Clexane significant inhibition of thrombus formation was observed. This antithrombotic effect lasted longer than 6 h but less than 8 h. In dose of 0.05 mg/kg after iv injection Clexane showed significant thrombolytic activity. In conclusion, further investigations are needed to optimize prophylactic and therapeutic use of low molecular heparins.