Comparative effects of enoxaparin and heparin on arterial and venous clot lysis with alteplase in dogs.
The effects of Enoxaparin with a specific anti-thrombin (anti-IIa) activity of 32 U/mg and a specific anti-factor-XA (anti-Xa) activity of 96 U/mg, and of heparin with a specific anti-IIa and anti-Xa activity of 192 U/mg, on thrombolysis with alteplase (Actilyse) were compared in a randomized blinded study using a combined arterial and venous thrombosis model in the dog. All dogs received an intravenous bolus of 5 mg/kg lysine-acetyl salicylate and 0.5 mg/kg alteplase over 60 min. Twenty-eight dogs were randomly assigned to seven treatment groups: placebo, Enoxaparin 1.5, 3 or 6 mg/kg, or heparin 0.5, 1 or 2 mg/kg, given as a 50% intravenous bolus and a 50% infusion over 2 h. Steady-state plasma levels ranged from 0.37 to 1.0 anti-IIa U/ml and 0.9 to 3.1 anti-Xa U/ml for Enoxaparin and from 0.4 to 2.3 anti-IIa U/ml and 0.42 to 3.2 anti-Xa U/ml for heparin. The activated thromboplastin time with 6 mg/kg Enoxaparin prolonged to 94 +/- 19 s and with 2 mg/kg heparin to > 150 s. The time to reflow was 120 +/- 36 min with placebo, 19 +/- 5 min with 6 mg/kg Enoxaparin (p = 0.03 vs control), and 22 +/- 5 min with 2 mg/kg of heparin (p = 0.03 vs control). Arterial patency, expressed in min reflow during the 180 min observation period correlated significantly with the dose of anticoagulant given (r = 0.73, p = 0.003 for Enoxaparin and r = 0.61, p = 0.012 for heparin).(ABSTRACT TRUNCATED AT 250 WORDS)
Center for Thrombosis and Vascular Research, University of Leuven, Belgium.
J M
JM
Stassen
H J
HJ
Rapold
I
I
Vanlinthout
D
D
Collen
D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives / Q000627:therapeutic use; D004285:Dogs; D004357:Drug Synergism; D005263:Femoral Artery; D005268:Femoral Vein; D006487:Hemostasis / Q000187:drug effects; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000627:therapeutic use*; D008239:Lysine / Q000031:analogs & derivatives / Q000627:therapeutic use; D011897:Random Allocation; D016037:Single-Blind Method; D015912:Thrombolytic Therapy; D013927:Thrombosis / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
D006495:Heparin, Low-Molecular-Weight; D006493:Heparin; D010959:Tissue Plasminogen Activator; D008239:Lysine; D001241:Aspirin; C010395:acetylsalicylic acid lysinate