title: Assessment of anticoagulation intensity and management of bleeding with old and new oral anticoagulants.
abstract: Warfarin is effective for the prevention and treatment of thromboembolism but produces variable anticoagulant effects and requires routine monitoring of the international normalized ratio (INR) to optimize the balance between efficacy and safety. The new oral anticoagulants (NOACs) have a more predictable anticoagulant effect and were recently demonstrated to be at least as efficacious and safe as warfarin despite being administered in fixed doses without routine coagulation monitoring. Specific laboratory tests have been developed to measure the anticoagulant effect of the NOACs but are not yet widely available, and the relation between drug levels and both coagulation test results and outcomes is uncertain. It remains to be demonstrated whether adjustment of the dose of NOACs, according to the results of laboratory testing, may lead to even greater efficacy and safety. The principles of bleeding management in patients treated with NOACs compared with patients receiving warfarin are similar. Most patients can be safely managed by interrupting drug treatment, performing local measures to stem the bleeding, and providing transfusion support as required. In patients with major or life-threatening bleeding and those requiring surgery, the anticoagulant effects of warfarin can be reversed using oral or intravenous vitamin K, fresh frozen plasma (FFP), and prothrombin complex concentrates (PCCs). Specific antidotes are under development for the NOACs but are not yet approved for clinical use. PCCs and recombinant factor VIIa may improve hemostasis in patients in whom bleeding develops during treatment with a NOAC, but their efficacy is unproven.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada. liew.aaron@gmail.com
authors.forename: Aaron
authors.initials: A
authors.lastname: Liew
authors.forename: John W
authors.initials: JW
authors.lastname: Eikelboom
authors.forename: Martin
authors.initials: M
authors.lastname: O'Donnell
authors.forename: Robert G
authors.initials: RG
authors.lastname: Hart
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000145:classification / Q000493:pharmacokinetics; D001281:Atrial Fibrillation / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D001682:Biological Availability; D001777:Blood Coagulation / Q000187:drug effects*; D001803:Blood Transfusion / Q000379:methods; D016903:Drug Monitoring / Q000379:methods*; D015507:Drugs, Investigational / Q000494:pharmacology; D006470:Hemorrhage / Q000139:chemically induced / Q000517:prevention & control / Q000628:therapy; D006801:Humans; D019934:International Normalized Ratio / Q000379:methods; D054539:Medication Therapy Management; D017063:Outcome Assessment, Health Care; D017410:Practice Guidelines as Topic; D016032:Randomized Controlled Trials as Topic; D013923:Thromboembolism / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D000925:Anticoagulants; D015507:Drugs, Investigational; D014859:Warfarin