Risk of bleeding in hospitalized patients on anticoagulant therapy: Prevalence and potential risk factors

Published:January 24, 2019DOI:


      • Prevalence of in-hospital bleeding in patients using anticoagulant therapy was 7.2%
      • Most common site of bleeding was a surgical site bleeding
      • Four risk factors were associated with bleeding events



      Bleeding is the most important complication of treatment with anticoagulant therapy. Although several studies have identified risk factors of bleeding in outpatients, no studies have been performed that evaluated prevalence and potential risk factors of bleeding in hospitalized patients treated with anticoagulant therapy.


      The primary objective of this study was to determine the prevalence of bleeding in anticoagulant users during hospitalization. The secondary objective was to identify potential risk factors of bleeding in hospitalized patients on anticoagulant therapy.
      A prospective, observational cohort study was conducted in two Dutch hospitals. Adult patients hospitalized between October 2015 and October 2016 treated with anticoagulant therapy were included. Bleeding was defined as a composite endpoint of major bleeding and non-major bleeding according to the International Society on Thrombosis and Heamostasis (ISTH) criteria. Data analysis was performed by multivariate logistic regression.


      The prevalence of in-hospital bleeding in patients using anticoagulant therapy was 7.2%; 95% confidence interval [95% CI] 5.5–9.1 (65 out of 906 patients). Multivariate logistic regression analysis indicated that female gender (adjusted odds ratio [ORadj] 2.1; 95% CI 1.2–3.7), high-bleeding-risk surgical procedure (ORadj 5.3; 95% CI 2.7–10.2), low-bleeding-risk surgical procedure (ORadj 4.9; 95% CI 1.9–12.6), and non-surgical interventions (ORadj 6.2; 95% CI 3.0–12.6) were associated with bleeding events in hospitalized patients treated with anticoagulants.


      The prevalence of bleeding in anticoagulant users during hospitalization was 7.2%. This study detected potential risk factors that can help to identify patients on anticoagulants who have an increased risk of bleeding during hospitalization.


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        • Ansell J.
        • Hirsh J.
        • Hylek E.
        • et al.
        Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).
        Chest. 2008; 133: 160S-198S
        • Wysowski D.K.
        • Nourjah P.
        • Swartz L.
        Bleeding complications with warfarin use.
        Arch Intern Med. 2007; 167: 1414-1419
        • Schulman S.
        • Beyth R.J.
        • Kearon C.
        • et al.
        Hemorrhagic complications of anticoagulant and thrombolytic treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).
        Chest. 2008; 133 (257S–98S)
        • Leendertse A.J.
        • Egberts A.C.
        • Stoker L.J.
        • et al.
        Frequency of and risk factors for preventable medication-related hospital admissions in the Netherlands.
        Arch Intern Med. 2008; 168: 1890-1896
        • Shoeb M.
        • Fang M.C.
        Assessing bleeding risk in patients taking anticoagulants.
        J Thromb Thrombolysis. 2013; 35: 312-319
        • Fitzmaurice D.A.
        • Blann A.D.
        • Lip G.Y.H.
        Bleeding risks of antithrombotic therapy.
        BMJ. 2002; 325: 828-831
        • Gage B.F.
        • Yan Y.
        • Milligan P.E.
        • et al.
        Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF).
        Am Heart J. 2006; 151: 713-719
        • Shireman T.I.
        • Mahnken J.D.
        • Howard P.A.
        • et al.
        Development of a contemporary bleeding risk model for elderly warfarin recipients.
        Chest. 2006; 130: 1390-1396
        • Pisters R.
        • Lane D.A.
        • Nieuwlaat R.
        • et al.
        A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey.
        Chest. 2010; 138: 1093-1100
        • Fang M.C.
        • Go A.S.
        • Chang Y.
        • et al.
        A new risk scheme to predict warfarin-associated hemorrhage: the ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) study.
        J Am Coll Cardiol. 2011; 58: 395-401
        • Beyth R.J.
        • Quinn L.M.
        • Landefeld C.S.
        Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin.
        Am J Med. 1998; 105: 91-99
        • Levine M.N.
        • Raskob G.
        • Beyth R.J.
        • et al.
        Hemorrhagic complications of anticoagulant treatment: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.
        Chest. 2004; 126: 287S-310S
        • van Walraven C.
        • Austin P.C.
        • Oake N.
        • et al.
        The effect of hospitalization on oral anticoagulation control: a population-based study.
        Thromb Res. 2007; 119: 705-714
        • Douketis J.D.
        • Spyropoulos A.C.
        • Kaatz S.
        • et al.
        Perioperative bridging anticoagulation in patients with atrial fibrillation.
        N Engl J Med. 2015; 373: 823-833
        • Dreijer A.R.
        • Kruip M.J.H.A.
        • Diepstraten J.
        • et al.
        Antithrombotic stewardship: a multidisciplinary team approach towards improving antithrombotic therapy outcomes during and after hospitalisation: a study protocol.
        BMJ Open. 2016; 6e011537
        • Levey A.S.
        • Bosch J.P.
        • Lewis J.B.
        • et al.
        A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group.
        Ann Intern Med. 1999; 130: 461-470
        • Douketis J.D.
        • Johnson J.A.
        • Turpie A.G.
        Low-molecular-weight heparin as bridging anticoagulation during interruption of warfarin. Assesment of a standardized periprocedural anticoagulation regimen.
        Arch Intern Med. 2004; 164: 1319-1326
        • Douketis J.D.
        • Spyropoulos A.C.
        • Spencer F.A.
        • Mayr M.
        • Jaffer A.K.
        • Eckman M.H.
        • et al.
        Perioperative management of antithrombotic therapy. Antithrombotic therapy and prevention of thrombosis, 9th ed: American college of chest physicians evidence-based clinical practice guidelines.
        Chest. 2012; 141: e326S-e350S
        • Stockley I.H.
        Stockley's Drug Interactions.
        11th ed. Pharmaceutical Press, London2016
        • Schulman S.
        • Kearon C.
        Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients.
        J Thromb Haemost. 2005; 3: 692-694
        • Schulman S.
        • Angerås U.
        • Bergqvist D.
        • et al.
        Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients.
        J Thromb Haemost. 2010; 8: 202-204
        • Hylek E.M.
        • Held C.
        • Alexander J.H.
        • et al.
        Major bleeding in patients with atrial fibrillation receiving apixaban or warfarin: the ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic events in Atrial Fibrillation): predictors, characteristics, and clinical outcomes.
        Am Coll Cardiol. 2014; 63: 2141-2147
        • Gómez-Outes A.
        • Terleira-Fernández A.I.
        • Calvo-Rojas G.
        • et al.
        Dabigatran, rivaroxaban, or apixaban versus warfarin in patients with nonvalvular atrial fibrillation: a systematic review and meta-analysis of subgroups.
        Thrombosis. 2013; 2013640723
        • Deitelzweig S.B.
        • Pinsky B.
        • Buysman E.
        • Lacey M.
        • et al.
        Bleeding as an outcome among patients with nonvalvular atrial fibrillation in a large managed care population.
        Clin Ther. 2013; 35: 1536-1545
        • Agresti A.
        An Introduction to Categorical Data Analysis.
        John Wiley & Sons, New York2007
        • Linkins L.A.
        • Choi P.T.
        • Douketis J.D.
        Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis.
        Ann Intern Med. 2003; 139: 893-900
        • Cosma Rochat M.
        • Waeber G.
        • Wasserfallen J.B.
        • et al.
        Hospitalized women experiencing an episode of excessive oral anticoagulation had a higher bleeding risk than men.
        J Womens Health. 2009; 18: 321-326
        • Reynolds H.R.
        • Farkouh M.E.
        • Lincoff A.M.
        • et al.
        Impact of female sex on death and bleeding after fibrinolytic treatment of mycocardial infarction in GUSTO V.
        Arch Intern Med. 2007; 167: 2054-2060
        • Van Rein N.
        • Biedermann J.S.
        • van der Meer F.J.M.
        • et al.
        Major bleeding risks of different low-molecular-weight heparin agents: a cohort study in 12 934 patients treated for acute venous thrombosis.
        J Thromb Haemost. 2017; 15: 1386-1391
        • GIP. Genees-en hulpmiddelen Informatie Project (GIP)
        The Drug Information System of National Health Care Institute.
        (accessed December 2017)
        • Torn M.
        • Bollen W.L.
        • van der Meer F.J.
        • et al.
        Risks of oral anticoagulant therapy with increasing age.
        Arch Intern Med. 2005; 165: 1527-1532
        • Carrasco-Garrido P.
        • Hernández-Barrera V.
        • Esteban-Hernández J.
        • et al.
        Adverse drug reactions to anticoagulants in Spain: analysis of the Spanish National Hospital Discharge Data (2010−2013).
        BMJ Open. 2017; 7e013224
        • Cadiou G.
        • Varin R.
        • Levesque H.
        • et al.
        Risk factors of vitamin K antagonist overcoagulation. A case-control study in unselected patients referred to an emergency department.
        Thromb Haemost. 2008; 100: 685-692
        • Harder S.
        • Thurmann P.
        Clinically important drug interactions with anticoagulants.
        An update Clin Pharmacokinet. 1996; 30: 416-444