title: Factor IXa as a target for anticoagulation in thrombotic disorders and conditions.
abstract: From acute coronary syndrome (ACS) to the prevention of cardioembolic events in patients with atrial fibrillation and thrombosis of mechanical heart valves, there is a quest to develop a new generation of anticoagulants. Perhaps the 'holy grail' of antithrombotic therapy is not only a drug that will prevent coagulation without promoting bleeding but also an anticoagulant that is easily reversible should the clinical need arise. Further, an optimally designed anticoagulant would have broad applications to include arterial, venous, hybrid conditions (atrial flutter and fibrillation) and nonbiological materials. Factor (F)IXa plays a pivotal part in tissue factor (TF)-mediated thrombin generation, and therefore represents a potentially promising target for drug development. FIXa activity has been targeted by multiple modalities, including oral inhibitors, RNA aptamers, monoclonal antibodies and synthetic active-site-blocking competitive inhibitors. Herein, we summarize the biochemistry of FIXa as it applies to thrombotic disorders and conditions, as well as the evolution of targeted therapies.
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Health and Disease, University of Cincinnati College of Medicine, Cincinnati, OH, USA. Electronic address: smileyda@ucmail.uc.edu.
authors.forename: Dia A
authors.initials: DA
authors.lastname: Smiley
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Health and Disease, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy; D000818:Animals; D000925:Anticoagulants / Q000009:adverse effects / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy; D015195:Drug Design; D015949:Factor IXa / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006470:Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000925:Anticoagulants; D013925:Thromboplastin; D015949:Factor IXa; D013917:Thrombin