Comparative study on the antithrombotic efficacy of four low-molecular-weight heparins in three different models of experimental venous thrombosis.
In a randomized, blind study, both the antithrombotic efficacy (reduction of thrombus weight) and potency (anti-Xa activity) of several commercially available low-molecular-weight heparins (LMWHs) were compared with those of unfractioned heparin (UFH) and placebo. Three different thrombogenic challenges were used: venous thrombosis was induced by direct endothelial damage in 60 New Zealand rabbits (group I), intracarotid injection of bovine thrombin in an additional series of 60 rabbits (group II), or after inferior-vena-cava ligature in 60 Wistar rats (group III). The drugs were administered subcutaneously 2 h before surgery in a blind fashion. The doses recommended for clinical practice were used (adjusted by body weight), except in group II animals, in whom doses were doubled. No differences were found between UFH and most LMWHs in terms of reduction of thrombus weight in group I animals. But UFH showed a weaker antithrombotic efficacy in the other two models. Similarly, one of the LMWHs used (Clexane) proved to be not as effective as the remainder. However, only clinical studies will provide enough information to verify these differences. Additionally, our findings confirm that the antithrombotic efficacy of a given drug differs according to the stimulus used to induce venous thrombosis.
Monreal
M
M
Unit of Experimental Thrombosis, Facultad de Veterinaria, Universidad Autonoma de Barcelona, Spain.
Silveira
P
P
Monreal
L
L
Monasterio
J
J
Angles
A M
AM
Lafoz
E
E
Lorente
L
L
D000818:Animals; D001778:Blood Coagulation Disorders / Q000188:drug therapy; D004195:Disease Models, Animal; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D008297:Male; D011817:Rabbits; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D013924:Thrombophlebitis / Q000188:drug therapy*
D006495:Heparin, Low-Molecular-Weight