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

Abstract

INTRODUCTION:

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.

MATERIALS AND METHODS:

The anticoagulant, antiplatelet, antithrombotic, and bleeding effects of AVE5026 in comparison to other heparins were investigated in this study.

RESULTS:

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.

CONCLUSIONS:

This superior safety efficacy index in animal models in comparison with other LMWH may translate into improved antithrombotic efficacy with decreased bleeding risk.

• Authors: Debra A Hoppensteadt, Angel Gray, Walter P Jeske, Jeanine M Walenga, Jawed Fareed
• Journal: Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis (Clin Appl Thromb Hemost) Vol. 20 Issue 6 Pg. 621-8 (Sep 2014) ISSN: 1938-2723 [Electronic] United States
• PMID: 23482722 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2013.

Chemical References

• AVE 5026
• Factor Xa Inhibitors
• Heparin

Topics

• Animals
• Disease Models, Animal
• Drug Evaluation, Preclinical
• Factor Xa Inhibitors (pharmacology)
• Heparin (analogs & derivatives, pharmacology)
• Male
• Rabbits
• Rats
• Rats, Wistar
• Thrombosis (blood, drug therapy)