The objective of this study was to compare the effectiveness of the
low molecular weight heparin,
enoxaparin (
Lovenox((R))), and
inogatran (a
direct thrombin inhibitor) in a canine electrolytic injury model of
venous thrombosis. Effectiveness was defined as the ability of either
drug to prolong the following parameters: activated partial thromboplastin time (aPTT), thrombin time (TT), prothrombin time (PT), and time to formation of an occlusive
thrombus in the vein. There were 5 dogs and 10 vessels for each group (the right and left femoral veins were used in each dog to measure time to occlusion). Dogs were randomly assigned to one of six groups: (1) saline controls; (2) low-dose
inogatran (0.075 mg/kg IV bolus followed by a 5 µg/kg/min infusion); (3) mid-dose
inogatran (0.25 mg/kg IV bolus followed by a 20 µg/kg/min infusion); (4) high-dose
inogatran (0.75 mg/kg IV bolus followed by a 50 µg/kg/min infusion); (5) low-dose
enoxaparin (100 units/kg IV bolus followed by a 50 U/kg/h infusion); and (6) high-dose
enoxaparin (200 U/kg IV bolus followed by a 100 U/kg/h infusion). Administration of
inogatran resulted in dose-dependent increases in aPTT, TT, and PT, and administration of
enoxaparin resulted in dose-dependent increases in aPTT and TT. There were no changes in hemodynamics. The time to occlusion in the control group averaged 81.7 +/- 9.9 minutes compared with 141.8 +/- 12.7, 185.8 +/- 17.6, and 226.9 +/- 8.8 minutes with the low, mid, and high doses of
inogatran, and 131 +/- 20.3, and 183.0 +/- 19.0 minutes with the low and high doses of
enoxaparin. Bleeding times were elevated by
inogatran and
enoxaparin, but no appreciable differences were detected between the two compounds. In summary, the
direct thrombin inhibitor inogatran, administered intravenously, was as effective as the
low molecular weight heparin enoxaparin in a canine model of
venous thrombosis induced by electrolytic injury, supporting the conclusion that
direct antithrombins may prove useful for prevention and treatment of
deep venous thrombosis.