title: Pharmacological effects and clinical applications of ultra low molecular weight heparins.
abstract: Heparin, one of the common anticoagulants, is clinically used to prevent and treat venous thromboembolism (VTE). Though it has been the drug of choice for many advanced medical and surgical procedures with a long history, the adverse events, such as bleeding, heparin-induced thrombocytopenia (HIT), allergic reactions, follow. Therefore, low molecular weight heparins (LMWHs) and ultra low molecular weight heparins (ULMWHs), with lower molecular weights, higher anti-FXa activity, longer half-life times and lower incidence of adverse events than unfractionated heparin (UFH), were researched and developed. Fondaparinux, a chemically synthesized ULMWH of pentasaccharide, has the same antithrombin III (AT-III)-binding sequence as found in UFH and LMWH. In addition, AVE5026 and RO-14, another two ULMWHs, are obtained by selective chemical depolymerization. In this paper, we review the preparation process, pharmacological effects and clinical applications of fondaparinux, AVE5026 and RO-14.
authors.affiliation: Key Laboratory of Chemical Biology of Natural Products (Ministry of Education), Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Sciences, Shandong University.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Liu
authors.forename: Shengli
authors.initials: S
authors.lastname: Ji
authors.forename: Juzheng
authors.initials: J
authors.lastname: Sheng
authors.forename: Fengshan
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000009:adverse effects / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects; D015195:Drug Design; D015951:Factor Xa / Q000378:metabolism; D065427:Factor Xa Inhibitors; D000077425:Fondaparinux; D006207:Half-Life; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000031:analogs & derivatives / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D015394:Molecular Structure; D008970:Molecular Weight; D011134:Polysaccharides / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D054556:Venous Thromboembolism / Q000188:drug therapy*
chemical_list: C542814:AVE 5026; D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; D011134:Polysaccharides; D006493:Heparin; D015951:Factor Xa; D000077425:Fondaparinux