title: Anticoagulant and Antithrombotic Actions of AVE5026, an Enriched Anti-Xa Hemisynthetic Ultra-Low-Molecular-Weight Heparin.
abstract: BACKGROUND
  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.
  
  
  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.affiliation: Loyola University Chicago, Maywood, IL, USA dhoppen@lumc.edu.
authors.forename: Debra A
authors.initials: DA
authors.lastname: Hoppensteadt
authors.affiliation: Loyola University Chicago, Maywood, IL, USA.
authors.forename: Angel
authors.initials: A
authors.lastname: Gray
authors.affiliation: Loyola University Chicago, Maywood, IL, USA.
authors.forename: Walter P
authors.initials: WP
authors.lastname: Jeske
authors.affiliation: Loyola University Chicago, Maywood, IL, USA.
authors.forename: Jeanine M
authors.initials: JM
authors.lastname: Walenga
authors.affiliation: Loyola University Chicago, Maywood, IL, USA.
authors.forename: Jawed
authors.initials: J
authors.lastname: Fareed
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D065427:Factor Xa Inhibitors / Q000494:pharmacology*; D006493:Heparin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy*
chemical_list: C542814:AVE 5026; D065427:Factor Xa Inhibitors; D006493:Heparin
keywords: antithrombotic; bleeding; enriched anti-Xa activity; safety; ultra-low-molecular-weight heparin