Effects of intravenous enoxaparin and intravenous inogatran in an electrolytic injury model of venous thrombosis in the dog

The objective of this study was to compare the effectiveness of the low mol ecular weight heparin, enoxaparin (Lovenox(R)), and inogatran (a direct thr ombin inhibitor) in a canine electrolytic injury model of venous thrombosis . Effectiveness was defined as the ability of either drug to prolong the fo llowing parameters: activated partial thromboplastin time (aPTT), thrombin time (TT), prothrombin time (PT), and time to formation of an occlusive thr ombus in the vein. There were 5 dogs and 10 vessels for each group (the rig ht and left femoral veins were used in each dog to measure time to occlusio n). Dogs were randomly assigned to one of six groups: (1) saline controls; (2) low-dose inogatran (0.075 mg/kg TV bolus followed by a 5 mu g/kg/min in fusion); (3) mid-dose inogatran (0.25 mg/kg IV bolus followed by a 20 mu g/ kg/min infusion); (4) high-dose inogatran (0.75 mg/kg TV bolus followed by a 50 mu g/kg/min infusion); (5) low-dose enoxaparin (100 units/kg TV bolus followed by a 50 U/kg/h infusion); and (6) high-dose enoxaparin (200 U/kg T V bolus followed by a 100 U/kg/h infusion). Administration of inogatran res ulted in dose-dependent increases in aPTT, TT, and PT, and administration o f enoxaparin resulted in dose-dependent increases in aPTT and TT. There wer e no changes in hemodynamics. The time to occlusion in the control group av eraged 81.7 +/- 9.9 minutes compared with 141.8 +/- 12.7, 185.8 +/- 17.6, a nd 226.9 +/- 8.8 minutes with the low, mid, and high doses of inogatran, an d 131 +/- 20.3, and 183.0 +/- 19.0 minutes with the low and high doses of e noxaparin. Bleeding times mere elevated by inogatran and enoxaparin, but no appreciable differences were detected between the two compounds. In summar y, the direct thrombin inhibitor inogatran, administered intravenously, was as effective as the low molecular weight heparin enoxaparin in a canine mo del of venous thrombosis induced by electrolytic injury, supporting the con clusion that direct antithrombins may prove useful for prevention and treat ment of deep venous thrombosis.