title: Factor Xa inhibitors: new anti-thrombotic agents and their characteristics.
abstract: Factor Xa (FXa) is a key enzyme that is positioned at the convergence of the intrinsic and extrinsic pathways in the blood coagulation cascade, and inactivation by a specific FXa inhibitor effectively prevents the generation of thrombin. Various types of low molecular weight (LMW) heparin, which function as semi-selective and indirect FXa inhibitors, are replacing unfractionated heparin (UFH) as agents for the prevention and treatment of venous thromboembolism (VTE), as well as in initial treatment for coronary events. Of those, heparinoid has been shown to be safer and more effective for the prevention of postoperative VTE than UFH, especially for treatment of heparin-induced thrombocytopenia (HIT). Further, synthetic pentasaccharide has been found to offer advantages over current thromboprophylactic regimens in a number of patients undergoing major orthopedic surgery. Other studies have shown that pentasaccharide is more effective for overall VTE in comparison with LMW heparin, though it was also associated with an increased rate of major bleeding. Synthetic, selective, and direct inhibitors to FXa, such as DX-9065a, are highly potent and orally bioavailable antithrombotic agents that have demonstrated an improved side effect profile, probably by allowing sufficient thrombin to remain for platelet activation and normal hemostasis, while preventing pathological thrombus formation. For thrombosis therapy, the most desirable type of antithrombotic agent is an orally active drug that has a broad range of effective doses and no hemorrhagic side effects. Presently, many types of direct inhibitors are in various stages of clinical trials and expected to provide significant benefits as compared to currently utilized therapy strategies.
authors.affiliation: Deaptment of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan. iekom@hoku-iryo-u.ac.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ieko
authors.forename: Takashi
authors.initials: T
authors.lastname: Tarumi
authors.forename: Toru
authors.initials: T
authors.lastname: Nakabayashi
authors.forename: Mika
authors.initials: M
authors.lastname: Yoshida
authors.forename: Sumiyoshi
authors.initials: S
authors.lastname: Naito
authors.forename: Takao
authors.initials: T
authors.lastname: Koike
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use; D001760:Bleeding Time; D001777:Blood Coagulation; D002809:Chondroitin Sulfates / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003871:Dermatan Sulfate / Q000627:therapeutic use; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D000077425:Fondaparinux; D006487:Hemostasis; D006493:Heparin / Q000737:chemistry / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D006497:Heparan Sulfate / Q000627:therapeutic use; D006801:Humans; D008954:Models, Biological; D008956:Models, Chemical; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011134:Polysaccharides / Q000737:chemistry / Q000627:therapeutic use; D013923:Thromboembolism / Q000188:drug therapy
chemical_list: D000925:Anticoagulants; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D000077425:Fondaparinux; D006493:Heparin; D006495:Heparin, Low-Molecular-Weight; D006497:Heparan Sulfate; D010975:Platelet Aggregation Inhibitors; D011134:Polysaccharides; C035838:danaparoid