Ambulatory, Office-based, and Geriatric Urology| Volume 114, P27-32, April 2018

Incidence of Visible Hematuria Among Antithrombotic Agents: A Systematic Review of Over 175,000 Patients

Published:November 27, 2017DOI:


      To determine the probability of visible hematuria with antithrombotic agents and to evaluate association of urologic etiology in antithrombotic-related hematuria.


      Preferred Reporting Items in Systematic Reviews and Meta-Analyses guidelines were followed to conduct a systematic review using search engines PUBMED and SCOPUS with the terms “(hematuria) OR (haematuria) OR urinary bleeding)) AND ((anticoagulants) OR anticoagulation) OR noac) OR novel anticoagulants) OR antiplatelet) OR dabigatran) OR rivaroxaban) OR apixaban) OR warfarin) OR aspirin) OR heparin) OR dipyridamole).” Raw data were used to perform a pooled analysis. Chi-square and logistic regression analysis were used for statistical analyses.


      Twenty-two studies describing 175,114 patients met inclusion criteria. Odds ratio of hematuria with warfarin to rivoraxaban was 33 and warfarin to dabigatran was 16. The odds ratio of hematuria for oral anticoagulant (26.7%) to prophylactic parenteral anticoagulant (1.1%) agents was 9.6. Antiplatelet agents are 76 times less likely to cause hematuria compared to anticoagulants. Odds of hematuria with aspirin were 6.7 times the odds with clopidogrel and 3.5 times the odds with ticagrelor. Dabigatran was 198 times more likely to cause major hematuria compared to warfarin, whereas clopidogrel is 1.2 times more likely to cause major hematuria compared to aspirin. Urologic pathology was identified in 44% (234/532) of cases, malignancy in 24%.


      Warfarin use poses the greatest risk for hematuria but is unlikely to cause major hematuria, whereas novel antithrombotic agents are more commonly associated with major hematuria. This review further characterizes the risk profile of antithrombotic agents and associated hematuria to equip clinicians with knowledge to choose an appropriate antithrombotic agent in patients with high-risk hematuria.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Urology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Landefeld C.S.
        • Beyth R.J.
        Anticoagulant-related bleeding: clinical epidemiology, prediction, and prevention.
        Am J Med. 1993; 95: 315-328
        • Culkin D.J.
        • Exaire E.J.
        • Green D.
        • et al.
        Anticoagulation and antiplatelet therapy in urological practice: ICUD/AUA review paper.
        J Urol. 2014; 192: 1026-1034
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • Altman D.G.
        Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement.
        BMJ. 2009; 339
        • Acanfora D.
        • Acanfora C.
        • Scicchitano P.
        • et al.
        Safety and feasibility of treatment with rivaroxaban for non-canonical indications: a case series analysis.
        Clin Drug Investig. 2016; 36: 857-862
        • Benavente L.
        • Calleja S.
        • de la Vega V.
        • Garcia J.
        • Lahoz C.H.
        Oral anticoagulation in elderly patients as secondary prevention of cardioembolic strokes.
        Int Arch Med. 2010; 3: 8
        • Berthelot E.
        • Lavenu-Bombled C.
        • Orostegui-Giron L.
        • Desconclois C.
        • Assayag P.
        Impaired renal function and bleeding in elderly treated with dabigatran.
        Blood Coagul Fibrinolysis. 2014; 25: 618-620
        • Chan K.E.
        • Edelman E.R.
        • Wenger J.B.
        • Thadhani R.I.
        • Maddux F.W.
        Dabigatran and rivaroxaban use in atrial fibrillation patients on hemodialysis.
        Circulation. 2015; 131: 972-979
        • Chen Y.C.
        • Chi C.C.
        • Chan F.C.
        • Wen Y.W.
        Low molecular weight heparin for prevention of microvascular occlusion in digital replantation.
        Cochrane Database Syst Rev. 2013; (CD009894)
        • DeFelipe-Mimbrera A.
        • Alonso Canovas A.
        • Guillan M.
        • et al.
        Dabigatran in secondary stroke prevention: clinical experience with 106 patients.
        Biomed Res Int. 2014; 2014 (567026)
        • DiNicolantonio J.J.
        • D'Ascenzo F.
        • Tomek A.
        • Chatterjee S.
        • Niazi A.K.
        • Biondi-Zoccai G.
        Clopidogrel is safer than ticagrelor in regard to bleeds: a closer look at the PLATO trial.
        Int J Cardiol. 2013; 168: 1739-1744
        • Glund S.
        • Stangier J.
        • Schmohl M.
        • et al.
        Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial.
        Lancet. 2015; 386: 680-690
        • Hori M.
        • Matsumoto M.
        • Tanahashi N.
        • et al.
        Safety and efficacy of adjusted dose of rivaroxaban in Japanese patients with non-valvular atrial fibrillation: subanalysis of J-ROCKET AF for patients with moderate renal impairment.
        Circ J. 2013; 77: 632-638
        • Jasuja G.K.
        • Reisman J.I.
        • Miller D.R.
        • et al.
        Identifying major hemorrhage with automated data: results of the Veterans Affairs study to improve anticoagulation (VARIA).
        Thromb Res. 2013; 131: 31-36
        • Lasek-Bal A.
        • Urbanek T.
        • Gierek D.
        Analysis of the efficacy and safety of new oral anticoagulant drugs in the secondary stroke prevention in patients with AF: single center experience based on 311 patients.
        Int Angiol. 2015; 34: 552-561
        • Lavitola Pde L.
        • Spina G.S.
        • Sampaio R.O.
        • Tarasoutchi F.
        • Grinberg M.
        Bleeding during oral anticoagulant therapy: warning against a greater hazard.
        Arq Bras Cardiol. 2009; 93: 174-179
        • Leonardi M.J.
        • McGory M.L.
        • Ko C.Y.
        The rate of bleeding complications after pharmacologic deep venous thrombosis prophylaxis: a systematic review of 33 randomized controlled trials.
        Arch Surg. 2006; 141 (discussion 797-799): 790-797
        • Li J.
        • Jing J.
        • Zhou Y.
        • Yao Y.
        • Zhan J.
        [Comparison of rivaroxaban and enoxaparin on blood loss after total knee arthroplasty].
        Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2014; 28: 26-29
        • Lim A.K.
        • Campbell D.A.
        Haematuria and acute kidney injury in elderly patients admitted to hospital with supratherapeutic warfarin anticoagulation.
        Int Urol Nephrol. 2013; 45: 561-570
        • Serebruany V.
        • Tomek A.
        Missed bleeding events after ticagrelor in PEGASUS trial: massive non-compliance, information censoring, or both?.
        Int J Cardiol. 2016; 215: 214-216
        • Sjalander A.
        • Friberg B.
        • Svensson P.
        • Stigendal L.
        • Lethagen S.
        Menorrhagia and minor bleeding symptoms in women on oral anticoagulation.
        J Thromb Thrombolysis. 2007; 24: 39-41
        • Stepanyan G.
        • Badhwar N.
        • Lee R.J.
        • et al.
        Safety of new oral anticoagulants for patients undergoing atrial fibrillation ablation.
        J Interv Card Electrophysiol. 2014; 40: 33-38
        • Tsivgoulis G.
        • Krogias C.
        • Sands K.A.
        • et al.
        Dabigatran etexilate for secondary stroke prevention: the first year experience from a multicenter short-term registry.
        Ther Adv Neurol Disord. 2014; 7: 155-161
        • Schaefer J.K.
        • McBane R.D.
        • Wysokinski W.E.
        How to choose appropriate direct oral anticoagulant for patient with nonvalvular atrial fibrillation.
        Ann Hematol. 2016; 95: 437-449
        • Pokorney S.D.
        • Sherwood M.W.
        • Becker R.C.
        Clinical strategies for selecting oral anticoagulants in patients with atrial fibrillation.
        J Thromb Thrombolysis. 2013; 36: 163-174
        • Davis R.
        • Jones S.
        • Barocas D.A.
        • et al.
        Diagnosis, evaluation and follow-up of asymptomatic microhematuria (AMH) in adults: AUA guideline.
        J Urol. 2012; 188: 2473-2478
        • Mladenov B.S.
        • Mariyanovski V.
        • Hadzhiyska V.
        Macroscopic hematuria in patients on anticoagulation therapy.
        Cent European J Urol. 2015; 68: 330-333
        • Antoniewicz A.A.
        • Zapala L.
        • Poletajew S.
        • Borowka A.
        Macroscopic hematuria—a leading urological problem in patients on anticoagulant therapy: is the common diagnostic standard still advisable?.
        ISRN Urol. 2012; 2012 (710734)
        • Ellis G.
        • John Camm A.
        • Datta S.N.
        Novel anticoagulants and antiplatelet agents; a guide for the urologist.
        BJU Int. 2015; 116: 687-696
        • Hu T.Y.
        • Vaidya V.R.
        • Asirvatham S.J.
        Reversing anticoagulant effects of novel oral anticoagulants: role of ciraparantag, andexanet alfa, and idarucizumab.
        Vasc Health Risk Manag. 2016; 12: 35-44
        • Mariani A.J.
        • Mariani M.C.
        • Macchioni C.
        • Stams U.K.
        • Hariharan A.
        • Moriera A.
        The significance of adult hematuria: 1,000 hematuria evaluations including a risk-benefit and cost-effectiveness analysis.
        J Urol. 1989; 141: 350-355
        • Avidor Y.
        • Nadu A.
        • Matzkin H.
        Clinical significance of gross hematuria and its evaluation in patients receiving anticoagulant and aspirin treatment.
        Urology. 2000; 55: 22-24