POTENTIATING EFFECTS OF ANTICOAGULANTS AND ANTIPLATELET AGENTS ON STREPTOKINASE-INDUCED THROMBOLYSIS IN THE RABBIT

Current thrombolytic strategies have a number of important shortcomings including resistance to recanalisation, development of acute reocclusion and serious haemorrhage. The purpose of this study was to investigate whether the lysis of venous thrombi by streptokinase could be enhanced by standard heparin, hirudin (rHV2-Lys 47), aspirin or clopidogrel, an analogue of ticlopidine. The activity of these compounds was evaluated by following the lysis of radiolabelled fibrin under a continuous infusion of streptokinase (4000 U/kg/h-4h). Streptokinase alone induced 45% thrombolysis when compared to saline. The i.v. bolus co-administration of hirudin (75-150-750 mug/kg), heparin (100 IU/kg), aspirin (100 mg/kg) or clopidogrel (10 mg/kg) enhanced thrombolysis with streptokinase. Under these various treatments, thrombolysis as measured by [I-125]-fibrinogen lysis increased to 55%, 64%, 79%, 60%, 54% and 59% respectively. These effects were related to the respective antithrombotic activities of these compounds, as evidenced by their anticoagulant or antiaggregant activities measured in parallel. However, efficacy of these compounds was achieved without additional prolongation of the template bleeding time observed with streptokinase alone. Thus, the concomitant use of antithrombotic agents during streptokinase therapy may prove to be helpful in preventing thrombus accretion and thus facilitating clot lysis.