Newly Published
Critical Care Medicine  |   April 2017
Management of Severe Bleeding in Patients Treated with Direct Oral Anticoagulants: An Observational Registry Analysis
Author Notes
  • From the Department of Anesthesiology and Intensive Care Medicine, Grenoble-Alpes University Hospital, Grenoble, France (P.A.); Department of Anesthesiology and Intensive Care Medicine, Assistance Publique-Hôpitaux de Paris, Cochin University Hospital, Paris Descartes University, Paris, France (C.-M.S.); Department of Hematology, Toulouse University Hospital, Toulouse, France (P. Sié, V.M.); Department of Anesthesiology and Intensive Care Medicine, Clermont-Ferrand University Hospital, Clermont-Ferrand, France (S.K.); Laboratory of Hematology, La Timone Hospital; INSERM, UMR_S 1062, Nutrition Obesity and Risk of Thrombosis; Nutrition Obesity and Risk of Thrombosis, Aix-Marseille University, UMR_S 1062, Marseille, France (P. Suchon); Department of Emergency Medicine, Saint Etienne University Hospital, Saint Etienne, France (A.V.); Department of Anesthesiology and Intensive Care Medicine, Hospices Civils de Lyon, Lyon Sud University Hospital, Pierre Benite, France (J.S.D.); Department of Hematology, Tours University Hospital, Tours, France (Y.G.); Department of Anesthesiology and Intensive Care Medicine, Brest University Hospital, Brest, France (L.B.); Department of Hematology, Dijon University Hospital, Dijon, France (E.d.M.); and Center of Clinical Investigation (P.R., J.-L.B.), Biostatistic Unit (S.T.), and Department of Vascular Medicine (G.P.), Grenoble Alpes University Hospital, Techniques pour l′Evaluation et la Modélisation des Actions de Santé (ThEMAS), Techniques de l′Ingénierie Médicale et de la Complexité (TIMC), Unité Mixte de Recherche (UMR), CNRS 5525, Université Grenoble-Alpes, Grenoble, France.
  • Clermont-Ferrand University Hospital, Clermont-Ferrand, France (n = 67)
  • Clermont-Ferrand University Hospital, Clermont-Ferrand, France (n = 67)
  • Clermont-Ferrand University Hospital, Clermont-Ferrand, France (n = 67)
  • Clermont-Ferrand University Hospital, Clermont-Ferrand, France (n = 67)
  • Clermont-Ferrand University Hospital, Clermont-Ferrand, France (n = 67)
  • Toulouse University Hospital, Toulouse, France (n = 66)
  • Assistance Publique- Hôpitaux de Marseille, Marseille, France (n = 64)
  • Assistance Publique- Hôpitaux de Marseille, Marseille, France (n = 64)
  • Assistance Publique- Hôpitaux de Marseille, Marseille, France (n = 64)
  • Assistance Publique- Hôpitaux de Marseille, Marseille, France (n = 64)
  • Grenoble University Hospital, Grenoble, France (n = 56)
  • Grenoble University Hospital, Grenoble, France (n = 56)
  • Grenoble University Hospital, Grenoble, France (n = 56)
  • Saint Etienne University Hospital, Saint Etienne, France (n = 55)
  • Saint Etienne University Hospital, Saint Etienne, France (n = 55)
  • Saint Etienne University Hospital, Saint Etienne, France (n = 55)
  • Hospices Civils de Lyon, Lyon-Sud University Hospital, Pierre Benite, France (n = 48)
  • Hospices Civils de Lyon, Lyon-Sud University Hospital, Pierre Benite, France (n = 48)
  • Hospices Civils de Lyon, Lyon-Sud University Hospital, Pierre Benite, France (n = 48)
  • Hospices Civils de Lyon, Lyon-Sud University Hospital, Pierre Benite, France (n = 48)
  • Tours University Hospital, Tours, France (n = 46)
  • Brest University Hospital, Brest, France (n = 42)
  • Dijon University Hospital, Dijon, France (n = 39)
  • Strasbourg University Hospital, Strasbourg, France (n = 29)
  • Strasbourg University Hospital, Strasbourg, France (n = 29)
  • Strasbourg University Hospital, Strasbourg, France (n = 29)
  • Bordeaux University Hospital, Bordeaux, France (n = 27)
  • Assistance Publique-Hôpitaux de Paris, Georges Pompidou University Hospital, Paris, France (n = 23)
  • Assistance Publique-Hôpitaux de Paris, Georges Pompidou University Hospital, Paris, France (n = 23)
  • Assistance Publique-Hôpitaux de Paris, Georges Pompidou University Hospital, Paris, France (n = 23)
  • Agen General Hospital, Agen, France (n = 21)
  • Agen General Hospital, Agen, France (n = 21)
  • Annecy Regional Hospital, Annecy, France (n = 19)
  • Annecy Regional Hospital, Annecy, France (n = 19)
  • Annecy Regional Hospital, Annecy, France (n = 19)
  • Annecy Regional Hospital, Annecy, France (n = 19)
  • Centre Médico-Chirurgical Foch, Suresnes, France (n = 18)
  • Assistance Publique-Hôpitaux de Paris, Bicêtre University Hospital, Le Kremlin Bicêtre, France (n = 17)
  • Assistance Publique-Hôpitaux de Paris, Bicêtre University Hospital, Le Kremlin Bicêtre, France (n = 17)
  • Assistance Publique-Hôpitaux de Paris, Cochin University Hospital, Paris, France (n = 13)
  • Assistance Publique-Hôpitaux de Paris, Cochin University Hospital, Paris, France (n = 13)
  • Rennes University Hospital, Rennes, France (n = 11)
  • Rennes University Hospital, Rennes, France (n = 11)
  • Rennes University Hospital, Rennes, France (n = 11)
  • Rennes University Hospital, Rennes, France (n = 11)
  • Brugmann University Hospital, Brussels, Belgium, (n = 10)
  • Montpellier University Hospital, Montpellier, France (n = 10)
  • Montpellier University Hospital, Montpellier, France (n = 10)
  • Montpellier University Hospital, Montpellier, France (n = 10)
  • Hospices Civils de Lyon, Edouard Herriot University Hospital, Lyon, France (n = 8)
  • Hospices Civils de Lyon, Edouard Herriot University Hospital, Lyon, France (n = 8)
  • Nantes University Hospital, Nantes, France (n = 7)
  • Nantes University Hospital, Nantes, France (n = 7)
  • Nantes University Hospital, Nantes, France (n = 7)
  • Assistance Publique-Hôpitaux de Paris, Bichat University Hospital, Paris, France (n = 6)
  • Assistance Publique-Hôpitaux de Paris, Bichat University Hospital, Paris, France (n = 6)
  • Assistance Publique-Hôpitaux de Paris, Beaujon University Hospital, Clichy, France (n = 5)
  • Assistance Publique-Hôpitaux de Paris, Beaujon University Hospital, Clichy, France (n = 5)
  • Alpes Léman Hospital, Contamine sur Arve, France (n = 5)
  • Groupe Hospitalier Mutualiste, Grenoble, France (n = 4)
  • Groupe Hospitalier Mutualiste, Grenoble, France (n = 4)
  • Angers University Hospital, Angers, France (n = 4)
  • Angers University Hospital, Angers, France (n = 4)
  • Chambéry General Hospital, Chambéry, France (n = 3)
  • Chambéry General Hospital, Chambéry, France (n = 3)
  • Chambéry General Hospital, Chambéry, France (n = 3)
  • Amiens University Hospital, Amiens, France (n = 3)
  • Saint Anne Military Hospital, Toulon, France (n = 2)
  • Saint Anne Military Hospital, Toulon, France (n = 2)
  • Lille University Hospital, Lille, France (n = 1)
  • Nimes University Hospital, Nimes, France (n = 1)
  • Gap General Hospital, Gap, France (n = 1)
  • Castres General Hospital, Castres, France (n = 1)
  • Rotschild Foundation, Paris, France (n = 1).
  • This is a Coagulation 2016 submission.
    This is a Coagulation 2016 submission.×
  • Submitted for publication July 28, 2016. Accepted for publication February 23, 2017.
    Submitted for publication July 28, 2016. Accepted for publication February 23, 2017.×
  • *Members of the Gestes Invasifs et Hémorragies chez les Patients Traités par les Nouveaux Anticoagulants Oraux (GIHP-NACO) Study Group are listed in the appendix.
    Members of the Gestes Invasifs et Hémorragies chez les Patients Traités par les Nouveaux Anticoagulants Oraux (GIHP-NACO) Study Group are listed in the appendix.×
  • Research Support: This study was supported by an unrestricted grant from Octapharma (Boulogne-Billancourt, France), CSL-Behring (Marburg, Germany), and LFB (Les Ulis, France).
    Research Support: This study was supported by an unrestricted grant from Octapharma (Boulogne-Billancourt, France), CSL-Behring (Marburg, Germany), and LFB (Les Ulis, France).×
  • Competing Interests: Dr. Albaladejo and Dr. Samama report personal fees and nonfinancial support from Bayer (Lyon, France), Boehringer Ingelheim (Paris, France), Daiichi Sankyo (Rueil-Malmaison, France), Bristol-Myers Squibb (Rueil-Malmaison, France), and Pfizer (Paris, France) outside the submitted work; Dr. Gruel reports personal fees from Boehringer Ingelheim (Paris, France) and Bristol-Myers Squibb (Rueil-Malmaison, France) and personal fees and nonfinancial support from Bayer (Lyon, France) outside the submitted work. The other authors declare no competing interests.
    Competing Interests: Dr. Albaladejo and Dr. Samama report personal fees and nonfinancial support from Bayer (Lyon, France), Boehringer Ingelheim (Paris, France), Daiichi Sankyo (Rueil-Malmaison, France), Bristol-Myers Squibb (Rueil-Malmaison, France), and Pfizer (Paris, France) outside the submitted work; Dr. Gruel reports personal fees from Boehringer Ingelheim (Paris, France) and Bristol-Myers Squibb (Rueil-Malmaison, France) and personal fees and nonfinancial support from Bayer (Lyon, France) outside the submitted work. The other authors declare no competing interests.×
  • Correspondence: Address correspondence to Dr. Albaladejo: Department of Anesthesiology and Intensive Care Medicine, Grenoble-Alpes University Hospital, 38043 Grenoble, France. PAlbaladejo@chu-grenoble.fr. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Critical Care Medicine / Coagulation and Transfusion / Critical Care
Critical Care Medicine   |   April 2017
Management of Severe Bleeding in Patients Treated with Direct Oral Anticoagulants: An Observational Registry Analysis
Anesthesiology Newly Published on April 20, 2017. doi:10.1097/ALN.0000000000001631
Anesthesiology Newly Published on April 20, 2017. doi:10.1097/ALN.0000000000001631
Abstract

Background: The use of prothrombin complex concentrates and the role of plasma concentration of anticoagulants in the management of bleeding in patients treated with direct oral anticoagulants are still debated. Our aim was to describe management strategies and outcomes of severe bleeding events in patients treated with direct oral anticoagulants.

Methods: We performed a prospective cohort study of 732 patients treated with dabigatran, rivaroxaban, or apixaban hospitalized for severe bleeding, included prospectively in the registry from June 2013 to November 2015.

Results: Bleeding was gastrointestinal or intracranial in 37% (212 of 732) and 24% (141 of 732) of the cases, respectively. Creatinine clearance was lower than 60 ml/min in 61% (449 of 732) of the cases. The plasma concentration of direct oral anticoagulants was determined in 62% (452 of 732) of the cases and was lower than 50 ng/ml or higher than 400 ng/ml in 9.2% (41 of 452) and in 6.6% (30 of 452) of the cases, respectively. Activated or nonactivated prothrombin complex concentrates were administered in 38% of the cases (281 of 732). Mortality by day 30 was 14% (95% CI, 11 to 16).

Conclusions: Management of severe bleeding in patients treated with direct oral anticoagulants appears to be complex. The use of prothrombin complex concentrates differs depending on bleeding sites and direct oral anticoagulant plasma concentrations. Mortality differs according to bleeding sites and was similar to previous estimates.