Prevention of experimental venous thrombosis in rabbits with different low molecular weight heparins, dermatan sulphate and hirudin.
In a randomized, blind study the antithrombotic efficacy of dermatan sulphate (DS), recombinant hirudin (r-hirudin) and four commercially available low molecular weight heparins (LMWHs) was investigated after intravenous administration in a jugular vein thrombus model in rabbits utilizing a combination of endothelial damage and flow reduction. The parameters observed were the frequency of visible thrombosis, the frequency of occlusive thrombosis and thrombus weights. DS and r-hirudin were investigated in one fixed dose and the LMWHs in prophylactic doses, adjusted to body weight, recommended in high-risk situations by the manufacturers. All substances effectively reduced the three observed parameters. DS and r-hirudin were equally or even more effective than the LMWHs. Although significant differences were not found between the individual LMWH treatments a visible trend cannot be overlooked in all three observed parameters. This cannot solely be explained by the different antifactor Xa activity doses given but increased antithrombotic activity was observed with declining antifactor Xa/antifactor IIa ratio. Our findings indicate that the different commercial LMWHs may differ in their antithrombotic activity when given in recommended doses adjusted to body weight in this experimental model. Dose range studies are required to clarify the thromboprophylactic efficacy of DS and r-hirudin in relation to the tested LMWHs.
Matthiasson
S E
SE
Department of Surgery, Lund University, Malmö General Hospital, Sweden.
Lindblad
B
B
Bergqvist
D
D
D000818:Animals; D001775:Blood Circulation; D003871:Dermatan Sulfate / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000293:injuries; D005069:Evaluation Studies as Topic; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D024764:Hirudin Therapy; D006629:Hirudins / Q000008:administration & dosage; D007601:Jugular Veins / Q000473:pathology; D008297:Male; D011817:Rabbits; D011897:Random Allocation; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D015912:Thrombolytic Therapy; D013924:Thrombophlebitis / Q000517:prevention & control*
D006495:Heparin, Low-Molecular-Weight; D006629:Hirudins; D011994:Recombinant Proteins; D003871:Dermatan Sulfate