Pierre Albaladejo1, Charles-Marc Samama, Pierre Sié, Sophie Kauffmann, Vincent Mémier, Pierre Suchon, Alain Viallon, Jean Stéphane David, Yves Gruel, Lorenn Bellamy, Emmanuel de Maistre, Pauline Romegoux, Sophie Thoret, Gilles Pernod, Jean-Luc Bosson. 1. 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).
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.
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.
Authors: Edelgard Lindhoff-Last; Eva Herrmann; Simone Lindau; Stavros Konstantinides; Oliver Grottke; Ulrike Nowak-Goettl; Jessica Lucks; Barbara Zydek; Christian von Heymann; Ingvild Birschmann; Ariane Sümnig; Jan Beyer-Westendorf; Sebastian Schellong; Patrick Meybohm; Andreas Greinacher Journal: Dtsch Arztebl Int Date: 2020-05-01 Impact factor: 5.594
Authors: Anne-Laure Sennesael; Anne-Sophie Larock; Jonathan Douxfils; Laure Elens; Gabriel Stillemans; Martin Wiesen; Max Taubert; Jean-Michel Dogné; Anne Spinewine; François Mullier Journal: Thromb J Date: 2018-11-12
Authors: Edelgard Lindhoff-Last; Ingvild Birschmann; Joachim Kuhn; Simone Lindau; Stavros Konstantinides; Oliver Grottke; Ulrike Nowak-Göttl; Jessica Lucks; Barbara Zydek; Christian von Heymann; Ariane Sümnig; Jan Beyer-Westendorf; Sebastian Schellong; Patrick Meybohm; Andreas Greinacher; Eva Herrmann Journal: Thromb Haemost Date: 2021-09-29 Impact factor: 6.681