Anticoagulant and Antithrombotic Actions of AVE5026, an Enriched Anti-Xa Hemisynthetic Ultra-Low-Molecular-Weight Heparin.

AVE5026 represents a new generation of ultra-low-molecular-weight heparin (LMWH) with high anti-Xa and low anti-IIa activities (anti Xa-IIa ratio >30). In addition, AVE5026 exhibits a relatively higher proportion of AT components. The anticoagulant, antiplatelet, antithrombotic, and bleeding effects of AVE5026 in comparison to other heparins were investigated in this study. AVE5026 demonstrated weak effects in the global clotting assays; however, in the amidolytic anti-Xa assay, AVE5026 produced strong inhibitory effects. AVE5026 showed no cross-reactivity with the heparin-induced thrombocytopenia antibodies in the platelet aggregation system. AVE5026 produced a dose-dependent antithrombotic response after intravenous (IV) and subcutaneous (SC) administration in thrombosis models. The relative bleeding effects of AVE5026 in a rat tail bleeding and rabbit blood loss model were negligible after both IV and SC administration. This superior safety efficacy index in animal models in comparison with other LMWH may translate into improved antithrombotic efficacy with decreased bleeding risk.