EFFECTS ON THROMBIN GENERATION OF SINGLE INJECTIONS OF HIRULOG(TM) INPATIENTS WITH CALF VEIN-THROMBOSIS

1. Study objective: To determine whether single injections of Hirulog, a direct thrombin inhibitor, can inhibit thrombin generation in patie nts with calf vein thrombosis and, if so, if the inhibition is sustain ed. 2. Design: Phase II open label cohort study. 3. Setting: Tertiary- care referral centres, university affiliated hospitals. 4. Patients: 1 0 patients with venographically-demonstrated calf vein thrombosis. 5. Intervention: Patients received a single injection of Hirulog, either 1.0 mg/kg subcutaneously or 0.6 mg/kg as a 15 min intravenous in fusio n. Prothrombin fragment (F1+2) levels, as an index of thrombin generat ion, were measured before as well as 6 h post- and 24 h post-Hirulog a dministration. Patients were followed with non-invasive tests to detec t thrombus extension into the proximal veins. 6. Results: There was a significant reduction in the levels of F1+2 with both regimens, 6 h af ter Hirulog. The F1+2 levels 24 h post-Hirulog showed a significant in crease relative to the 6 h post-Hirulog results. One patient developed thrombus extension into the popliteal vein and was treated with conve ntional anticoagulants. 7. Conclusion: The single injections of Hirulo g used in the study produced incomplete and temporary suppression of F 1+2. Complete and permanent inhibition of thrombin generation with Hir ulog in patients with calf vein thrombosis may require higher doses, m ultiple subcutaneous injections and/or prolonged intravenous infusion.