title: Organ-specific bleeding patterns of anticoagulant therapy: lessons from clinical trials.
abstract: Anticoagulants are effective at preventing and treating thrombosis, but can cause bleeding. For decades, vitamin K antagonists (VKAs) have been the only available oral anticoagulants. The development of non-VKA oral anticoagulants (NOACs), which inhibit either factor Xa or thrombin stoichiometrically, has provided alternatives to VKAs for several indications. The results of recent large-scale randomised controlled trials comparing NOACs with VKAs for the prevention of stroke in patients with non-valvular atrial fibrillation (AF) have produced some unexpected results. As a group, NOACs showed similar efficacy as warfarin, but a reduced risk of major bleeding. The reduction in bleeding with NOACs was greatest with intracranial hemorrhage. In contrast, the relative risk of gastro-intestinal bleeding was increased with some NOACs. In this review, we explore the potential mechanisms as well as the implications of these organ-specific bleeding patterns.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vanassche
authors.forename: Jack
authors.initials: J
authors.lastname: Hirsh
authors.affiliation: John Eikelboom, 237 Barton Street East, Hamilton, ON, L9K 1H8, Canada, Tel.: +1 905 527 4322 ext 40323, Fax: +1 905 521 1551, E-mail: eikelbj@mcmaster.ca.
authors.forename: John W
authors.initials: JW
authors.lastname: Eikelboom
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ginsberg
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications; D001779:Blood Coagulation Factors / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology; D065427:Factor Xa Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D019934:International Normalized Ratio; D007408:Intestinal Absorption; D020300:Intracranial Hemorrhages / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D009928:Organ Specificity; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000517:prevention & control; D019851:Thrombophilia / Q000188:drug therapy* / Q000209:etiology; D013925:Thromboplastin / Q000502:physiology; D014812:Vitamin K / Q000037:antagonists & inhibitors; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; D065427:Factor Xa Inhibitors; D014812:Vitamin K; D014859:Warfarin; D013925:Thromboplastin
keywords: Venous thrombosis; stroke prevention; thrombosis