A comparison of the antithrombotic effects of heparin and of low molecular weight heparins with increasing antifactor Xa/antifactor IIa ratio in the rabbit

Abstract

This study compares the ability of unfractionated heparin (UH) and of three low molecular weight heparins (LMWHs) to inhibit venous thrombosis growth in the rabbit. Logiparin (LHN-1), Fraxiparin (CY216) and CY222 were selected because they present very different antifactor Xa/antifactor IIa ratios: 1.7, 3.8 and 6.8 respectively. Heparins were delivered under continuous intravenous infusion for 4 h at increasing doses from 10 to 250 antifactor Xa U kg-1 h-1. The minimum dose providing the maximum inhibitory effect was 50 antifactor Xa U kg-1 h-1. On the basis of this system of units the four heparins were equipotent antithrombotic agents. Due to the highest antifactor Xa/antifactor IIa ratio, CY222 became the most potent antithrombotic agent when the doses were expressed in antithrombin units. Because UH is cleared faster than LMWHs at low dose regimen, the antifactor Xa steady state concentrations generated by the continuous infusion of any of the LMWHs were higher than those generated by UH. In addition the ex vivo antifactor Xa/antifactor IIa ratio of each of the LMWH was superior to the in vitro ratio. These results indicate that the antithrombotic activity of LMWH is not directly related to its subfraction catalysing thrombin inhibition.