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CC BY 4.0 · TH Open 2021; 05(02): e200-e210
DOI: 10.1055/s-0041-1730035
Review Article

Gastrointestinal Bleeding and Direct Oral Anticoagulants among Patients with Atrial Fibrillation: Risk, Prevention, Management, and Quality of Life

Paolo Zappulla 
1   Division of Cardiology, Centro alte specialità e trapianti (C.A.S.T.), Azienda Ospedaliero-Universitaria Policlinico “G. Rodolico - San Marco,” University of Catania, Catania, Italy
,
Valeria Calvi
1   Division of Cardiology, Centro alte specialità e trapianti (C.A.S.T.), Azienda Ospedaliero-Universitaria Policlinico “G. Rodolico - San Marco,” University of Catania, Catania, Italy
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Abstract

A significant problem for patients undergoing oral anticoagulation therapy is gastrointestinal bleeding (GIB), a problem that has become increasingly urgent following the introduction of direct oral anticoagulants (DOACs). Furthermore, in recent years a greater focus has been placed on the quality of life (QOL) of patients on long-term oral anticoagulant therapy, which necessitates changes in lifestyle, as well as posing an increased risk of bleeding without producing objective symptomatic relief. Here, we examine current evidence linked to GIB associated with oral anticoagulants, with a focus on randomized control trials, meta-analyses, and postmarketing observational studies. Rivaroxaban and dabigatran (especially the 150-mg bis-in-die dose) appeared to be linked to an increased risk of GIB. The risk of GIB was also greater when edoxaban was used, although this was dependent on the dose. Apixaban did not pose a higher risk of GIB in comparison with warfarin. We provided a summary of current knowledge regarding GIB risk factors for individual anticoagulants, prevention strategies that lower the risk of GIB and management of DOAC therapy after a GIB episode.

Keywords

oral anticoagulant - gastrointestinal bleeding - warfarin - rivaroxaban - dabigatran - edoxaban - apixaban


Publication History

Received: 11 February 2021

Accepted: 09 April 2021

Article published online:
16 June 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
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  • References

  • 1 Lane DA, Wood K. A patient's guide to taking the non-vitamin K antagonist oral anticoagulants (NOACs) for atrial fibrillation. Circulation 2015; 131 (16) e412-e415
    PubMedGoogle Scholar
  • 2 Hindricks G, Potpara T, Dagres N. et al ESC Scientific Document Group. ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS). Eur Heart J 2021; 42 (05) 373-498
    CrossrefPubMedGoogle Scholar
  • 3 Barnes GD, Ageno W, Ansell J, Kaatz S. Subcommittee on the Control of Anticoagulation of the International Society on Thrombosis and Haemostasis. Recommendation on the nomenclature for oral anticoagulants: communication from the SSC of the ISTH. J Thromb Haemost 2015; 13 (06) 1154-1156
    CrossrefPubMedGoogle Scholar
  • 4 Sherwood MW, Nessel CC, Hellkamp AS. et al. Gastrointestinal bleeding in patients with atrial fibrillation treated with rivaroxaban or warfarin: ROCKET AF trial. J Am Coll Cardiol 2015; 66 (21) 2271-2281
    CrossrefPubMedGoogle Scholar
  • 5 Agnelli G, Buller HR, Cohen A. et al; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013; 369 (09) 799-808
    CrossrefPubMedGoogle Scholar
  • 6 Wang Y, Kong MC, Lee LH, Ng HJ, Ko Y. Knowledge, satisfaction, and concerns regarding warfarin therapy and their association with warfarin adherence and anticoagulation control. Thromb Res 2014; 133 (04) 550-554
    CrossrefPubMedGoogle Scholar
  • 7 Keita I, Aubin-Auger I, Lalanne C. et al. Assessment of quality of life, satisfaction with anticoagulation therapy, and adherence to treatment in patients receiving long-course vitamin K antagonists or direct oral anticoagulants for venous thromboembolism. Patient Prefer Adherence 2017; 11: 1625-1634
    CrossrefPubMedGoogle Scholar
  • 8 Ware Jr JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992; 30 (06) 473-483
    CrossrefPubMedGoogle Scholar
  • 9 The WHOQOL Group. Development of the World Health Organization WHOQOL-BREF quality of life assessment. Psychol Med 1998; 28 (03) 551-558
    CrossrefPubMedGoogle Scholar
  • 10 Caruso S, Bandiera S, Cavallaro A, Cianci S, Vitale SG, Rugolo S. Quality of life and sexual changes after double transobturator tension-free approach to treat severe cystocele. Eur J Obstet Gynecol Reprod Biol 2010; 151 (01) 106-109
    CrossrefPubMedGoogle Scholar
  • 11 Vitale SG, Caruso S, Rapisarda AMC. et al. Biocompatible porcine dermis graft to treat severe cystocele: impact on quality of life and sexuality. Arch Gynecol Obstet 2016; 293 (01) 125-131
    CrossrefPubMedGoogle Scholar
  • 12 Vitale SG, Laganà AS, Noventa M. et al. Transvaginal bilateral sacrospinous fixation after second recurrence of vaginal vault prolapse: efficacy and impact on quality of life and sexuality. BioMed Res Int 2018; 2018: 5727165
    CrossrefPubMedGoogle Scholar
  • 13 Caruso S, Cianci S, Vitale SG, Fava V, Cutello S, Cianci A. Sexual function and quality of life of women adopting the levonorgestrel-releasing intrauterine system (LNG-IUS 13.5 mg) after abortion for unintended pregnancy. Eur J Contracept Reprod Health Care 2018; 23 (01) 24-31
    CrossrefPubMedGoogle Scholar
  • 14 Hankey GJ, Eikelboom JW. Dabigatran etexilate: a new oral thrombin inhibitor. Circulation 2011; 123 (13) 1436-1450
    CrossrefPubMedGoogle Scholar
  • 15 Salem J-E, Sabouret P, Funck-Brentano C, Hulot J-S. Pharmacology and mechanisms of action of new oral anticoagulants. Fundam Clin Pharmacol 2015; 29 (01) 10-20 DOI: 10.1111/fcp.12091.
    CrossrefPubMedGoogle Scholar
  • 16 Ruff CT, Giugliano RP, Braunwald E. et al. Association between edoxaban dose, concentration, anti-Factor Xa activity, and outcomes: an analysis of data from the randomised, double-blind ENGAGE AF-TIMI 48 trial. Lancet 2015; 385 (9984): 2288-2295
    CrossrefPubMedGoogle Scholar
  • 17 Connolly SJ, Ezekowitz MD, Yusuf S. et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361 (12) 1139-1151
    CrossrefPubMedGoogle Scholar
  • 18 Connolly SJ, Wallentin L, Ezekowitz MD. et al. The long-term multicenter observational study of dabigatran treatment in patients with atrial fibrillation (RELY-ABLE) study. Circulation 2013; 128 (03) 237-243
    CrossrefPubMedGoogle Scholar
  • 19 Patel MR, Mahaffey KW, Garg J. et al; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365 (10) 883-891
    CrossrefPubMedGoogle Scholar
  • 20 Halperin JL, Hankey GJ, Wojdyla DM. et al; ROCKET AF Steering Committee and Investigators. Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). Circulation 2014; 130 (02) 138-146
    CrossrefPubMedGoogle Scholar
  • 21 Granger CB, Alexander JH, McMurray JJV. et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365 (11) 981-992
    CrossrefPubMedGoogle Scholar
  • 22 Giugliano RP, Ruff CT, Braunwald E. et al; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013; 369 (22) 2093-2104
    CrossrefPubMedGoogle Scholar
  • 23 Loffredo L, Perri L, Violi F. Impact of new oral anticoagulants on gastrointestinal bleeding in atrial fibrillation: a meta-analysis of interventional trials. Dig Liver Dis 2015; 47 (05) 429-431
    CrossrefPubMedGoogle Scholar
  • 24 Holster IL, Valkhoff VE, Kuipers EJ, Tjwa ETTL. New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and meta-analysis. Gastroenterology 2013; 145 (01) 105-112.e15
    CrossrefPubMedGoogle Scholar
  • 25 Caldeira D, Barra M, Ferreira A. et al. Systematic review with meta-analysis: the risk of major gastrointestinal bleeding with non-vitamin K antagonist oral anticoagulants. Aliment Pharmacol Ther 2015; 42 (11, 12): 1239-1249
    CrossrefPubMedGoogle Scholar
  • 26 Miller CS, Dorreen A, Martel M, Huynh T, Barkun AN. Risk of gastrointestinal bleeding in patients taking non-vitamin K antagonist oral anticoagulants: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2017; 15 (11) 1674-1683.e3
    CrossrefPubMedGoogle Scholar
  • 27 Graham DJ, Reichman ME, Wernecke M. et al. Stroke, bleeding, and mortality risks in elderly medicare beneficiaries treated with dabigatran or rivaroxaban for nonvalvular atrial fibrillation. JAMA Intern Med 2016; 176 (11) 1662-1671
    CrossrefPubMedGoogle Scholar
  • 28 Hernandez I, Baik SH, Piñera A, Zhang Y. Risk of bleeding with dabigatran in atrial fibrillation. JAMA Intern Med 2015; 175 (01) 18-24
    CrossrefPubMedGoogle Scholar
  • 29 Abraham NS, Singh S, Alexander GC. et al. Comparative risk of gastrointestinal bleeding with dabigatran, rivaroxaban, and warfarin: population based cohort study. BMJ 2015; 350: h1857
    CrossrefPubMedGoogle Scholar
  • 30 Chang H-Y, Zhou M, Tang W, Alexander GC, Singh S. Risk of gastrointestinal bleeding associated with oral anticoagulants: population based retrospective cohort study. BMJ 2015; 350: h1585
    CrossrefPubMedGoogle Scholar
  • 31 Larsen TB, Rasmussen LH, Skjøth F. et al. Efficacy and safety of dabigatran etexilate and warfarin in “real-world” patients with atrial fibrillation: a prospective nationwide cohort study. J Am Coll Cardiol 2013; 61 (22) 2264-2273
    CrossrefPubMedGoogle Scholar
  • 32 Southworth MR, Reichman ME, Unger EF. Dabigatran and postmarketing reports of bleeding. N Engl J Med 2013; 368 (14) 1272-1274
    CrossrefPubMedGoogle Scholar
  • 33 Yao X, Abraham NS, Sangaralingham LR. et al. Effectiveness and safety of dabigatran, rivaroxaban, and apixaban versus warfarin in nonvalvular atrial fibrillation. J Am Heart Assoc 2016; 5 (06) e003725
    CrossrefPubMedGoogle Scholar
  • 34 Desai J, Kolb JM, Weitz JI, Aisenberg J. Gastrointestinal bleeding with the new oral anticoagulants--defining the issues and the management strategies. Thromb Haemost 2013; 110 (02) 205-212
    Article in Thieme ConnectPubMedGoogle Scholar
  • 35 Eikelboom JW, Wallentin L, Connolly SJ. et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation 2011; 123 (21) 2363-2372
    CrossrefPubMedGoogle Scholar
  • 36 Laursen SB, Hansen JM, Hallas J, Schaffalitzky de Muckadell OB. The excess long-term mortality in peptic ulcer bleeding is explained by nonspecific comorbidity. Scand J Gastroenterol 2015; 50 (02) 145-152
    CrossrefPubMedGoogle Scholar
  • 37 Hylek EM, Held C, Alexander JH. 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. J Am Coll Cardiol 2014; 63 (20) 2141-2147
    CrossrefPubMedGoogle Scholar
  • 38 Dans AL, Connolly SJ, Wallentin L. et al. Concomitant use of antiplatelet therapy with dabigatran or warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. Circulation 2013; 127 (05) 634-640
    CrossrefPubMedGoogle Scholar
  • 39 Chan EW, Lau WCY, Leung WK. et al. Prevention of dabigatran-related gastrointestinal bleeding with gastroprotective agents: a population-based study. Gastroenterology 2015; 149 (03) 586-95.e3
    CrossrefPubMedGoogle Scholar
  • 40 Hori M, Connolly SJ, Zhu J. et al; RE-LY Investigators. Dabigatran versus warfarin: effects on ischemic and hemorrhagic strokes and bleeding in Asians and non-Asians with atrial fibrillation. Stroke 2013; 44 (07) 1891-1896
    CrossrefPubMedGoogle Scholar
  • 41 Shimomura A, Nagata N, Shimbo T. et al. New predictive model for acute gastrointestinal bleeding in patients taking oral anticoagulants: A cohort study. J Gastroenterol Hepatol 2018; 33 (01) 164-171
    CrossrefPubMedGoogle Scholar
  • 42 Masclee GMC, Valkhoff VE, Coloma PM. et al. Risk of upper gastrointestinal bleeding from different drug combinations. Gastroenterology 2014; 147 (04) 784-792.e9 , quiz e13–e14
    CrossrefPubMedGoogle Scholar
  • 43 Leonard CE, Brensinger CM, Bilker WB. et al. Gastrointestinal bleeding and intracranial hemorrhage in concomitant users of warfarin and antihyperlipidemics. Int J Cardiol 2017; 228: 761-770
    CrossrefPubMedGoogle Scholar
  • 44 Westenbrink BD, Alings M, Granger CB. et al. Anemia is associated with bleeding and mortality, but not stroke, in patients with atrial fibrillation: Insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. Am Heart J 2017; 185: 140-149
    CrossrefPubMedGoogle Scholar
  • 45 Hu W-S, Sung F-C, Lin C-L. Aplastic anemia and risk of incident atrial fibrillation- a nationwide cohort study. Circ J 2018; 82 (05) 1279-1285
    CrossrefPubMedGoogle Scholar
  • 46 Gage BF, Yan Y, Milligan PE. et al. Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF). Am Heart J 2006; 151 (03) 713-719
    CrossrefPubMedGoogle Scholar
  • 47 Fang MC, Go AS, 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 (04) 395-401
    CrossrefPubMedGoogle Scholar
  • 48 O'Brien EC, Simon DN, Thomas LE. et al. The ORBIT bleeding score: a simple bedside score to assess bleeding risk in atrial fibrillation. Eur Heart J 2015; 36 (46) 3258-3264
    PubMedGoogle Scholar
  • 49 Connolly SJ, Eikelboom J, Joyner C. et al; AVERROES Steering Committee and Investigators. Apixaban in patients with atrial fibrillation. N Engl J Med 2011; 364 (09) 806-817
    CrossrefPubMedGoogle Scholar
  • 50 Steffel J, Verhamme P, Potpara TS. et al; ESC Scientific Document Group. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J 2018; 39 (16) 1330-1393
    CrossrefPubMedGoogle Scholar
  • 51 Wang C-L, Wu VC-C, Huang Y-T. et al. Safety and effectiveness of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with atrial fibrillation and anemia: a retrospective cohort study. J Am Heart Assoc 2019; 8 (09) e012029
    CrossrefPubMedGoogle Scholar
  • 52 Boos CJ, Brown L. Anticoagulation in atrial fibrillation and chronic heart failure: the risk and drug of choice. Curr Opin Cardiol 2016; 31 (02) 229-234
    CrossrefPubMedGoogle Scholar
  • 53 DiMarco JP, Flaker G, Waldo AL. et al; AFFIRM Investigators. Factors affecting bleeding risk during anticoagulant therapy in patients with atrial fibrillation: observations from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study. Am Heart J 2005; 149 (04) 650-656
    CrossrefPubMedGoogle Scholar
  • 54 Friberg L, Rosenqvist M, Lip GYH. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J 2012; 33 (12) 1500-1510
    CrossrefPubMedGoogle Scholar
  • 55 Chen F, Zhou Y, Wan Q, Yu P, Ma J, Hu J. Effect of non-vitamin K antagonist oral anticoagulants versus warfarin in heart failure patients with atrial fibrillation. Heart Fail Rev 2020; (e-pub ahead of print) DOI: 10.1007/s10741-020-09946-8.
    CrossrefPubMedGoogle Scholar
  • 56 Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJGM, Lip GYH. 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 (05) 1093-1100
    CrossrefPubMedGoogle Scholar
  • 57 Lip GYH, Frison L, Halperin JL, Lane DA. Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score. J Am Coll Cardiol 2011; 57 (02) 173-180
    CrossrefPubMedGoogle Scholar
  • 58 Davidson BL, Verheijen S, Lensing AWA. et al. Bleeding risk of patients with acute venous thromboembolism taking nonsteroidal anti-inflammatory drugs or aspirin. JAMA Intern Med 2014; 174 (06) 947-953
    CrossrefPubMedGoogle Scholar
  • 59 Lanas A, Benito P, Alonso J. et al; Spanish Society of Rhematology, Spanish Association of Gastroenterology, Spanish Society of Cardiology. Safe prescription recommendations for non steroidal anti-inflammatory drugs: consensus document ellaborated by nominated experts of three scientific associations (SER-SEC-AEG). Reumatol Clin 2014; 10 (02) 68-84
    CrossrefPubMedGoogle Scholar
  • 60 Abraham NS. New clinical paradigms for treating and preventing antiplatelet gastrointestinal bleeding. Curr Opin Gastroenterol 2017; 33 (06) 467-472
    CrossrefPubMedGoogle Scholar
  • 61 Lauffenburger JC, Rhoney DH, Farley JF, Gehi AK, Fang G. Predictors of gastrointestinal bleeding among patients with atrial fibrillation after initiating dabigatran therapy. Pharmacotherapy 2015; 35 (06) 560-568
    CrossrefPubMedGoogle Scholar
  • 62 Steinberg BA, Kim S, Piccini JP. et al; ORBIT-AF Investigators and Patients. Use and associated risks of concomitant aspirin therapy with oral anticoagulation in patients with atrial fibrillation: insights from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry. Circulation 2013; 128 (07) 721-728
    CrossrefPubMedGoogle Scholar
  • 63 Staudacher DL, Kaiser M, Hehrlein C, Bode C, Ahrens I. Triple antithrombotic therapy after percutaneous coronary intervention (PCI) in patients with indication for oral anticoagulation: data from a single center registry. PLoS One 2015; 10 (10) e0140101
    CrossrefPubMedGoogle Scholar
  • 64 Lanas A, García-Rodríguez LA, Arroyo MT. et al; Investigators of the Asociación Española de Gastroenterología (AEG). Effect of antisecretory drugs and nitrates on the risk of ulcer bleeding associated with nonsteroidal anti-inflammatory drugs, antiplatelet agents, and anticoagulants. Am J Gastroenterol 2007; 102 (03) 507-515
    CrossrefPubMedGoogle Scholar
  • 65 Nagata N, Niikura R, Yamada A. et al. Acute middle gastrointestinal bleeding risk associated with NSAIDs, antithrombotic drugs, and PPIs: a multicenter case-control study. PLoS One 2016; 11 (03) e0151332
    CrossrefPubMedGoogle Scholar
  • 66 Lué A, Lanas A. Protons pump inhibitor treatment and lower gastrointestinal bleeding: Balancing risks and benefits. World J Gastroenterol 2016; 22 (48) 10477-10481
    CrossrefPubMedGoogle Scholar
  • 67 Lanas-Gimeno A, Lanas A. Risk of gastrointestinal bleeding during anticoagulant treatment. Expert Opin Drug Saf 2017; 16 (06) 673-685
    CrossrefPubMedGoogle Scholar
  • 68 Sengupta N, Tapper EB, Patwardhan VR. et al. Risk factors for adverse outcomes in patients hospitalized with lower gastrointestinal bleeding. Mayo Clin Proc 2015; 90 (08) 1021-1029
    CrossrefPubMedGoogle Scholar
  • 69 Sherid M, Sifuentes H, Sulaiman S. et al. Risk of gastrointestinal bleeding with dabigatran: a head-to-head comparative study with rivaroxaban. Digestion 2014; 90 (02) 137-146
    CrossrefPubMedGoogle Scholar
  • 70 Weitz JI, Pollack Jr CV. Practical management of bleeding in patients receiving non-vitamin K antagonist oral anticoagulants. Thromb Haemost 2015; 114 (06) 1113-1126
    Article in Thieme ConnectPubMedGoogle Scholar
  • 71 Inohara T, Xian Y, Liang L. et al. Association of intracerebral hemorrhage among patients taking non-vitamin K antagonist vs vitamin K antagonist oral anticoagulants with in-hospital mortality. JAMA 2018; 319 (05) 463-473
    CrossrefPubMedGoogle Scholar
  • 72 van Ryn J, Stangier J, Haertter S. et al. Dabigatran etexilate--a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 2010; 103 (06) 1116-1127
    Article in Thieme ConnectPubMedGoogle Scholar
  • 73 Khadzhynov D, Wagner F, Formella S. et al. Effective elimination of dabigatran by haemodialysis. A phase I single-centre study in patients with end-stage renal disease. Thromb Haemost 2013; 109 (04) 596-605
    Article in Thieme ConnectPubMedGoogle Scholar
  • 74 Dusel CH, Grundmann C, Eich S, Seitz R, König H. Identification of prothrombin as a major thrombogenic agent in prothrombin complex concentrates. Blood Coagul Fibrinolysis 2004; 15 (05) 405-411
    CrossrefPubMedGoogle Scholar
  • 75 Milling Jr. TJ, Refaai MA, Sarode R. et al. Safety of a four-factor prothrombin complex concentrate versus plasma for vitamin k antagonist reversal: an integrated analysis of two phase IIIb clinical trials. Acad Emerg Med 2016; 23 (04) 466-475
    CrossrefPubMedGoogle Scholar
  • 76 Tomaselli GF, Mahaffey KW, Cuker A. et al. 2017 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants: a report of the American College of Cardiology Task Force on expert consensus decision pathways. J Am Coll Cardiol 2017; 70 (24) 3042-3067
    CrossrefPubMedGoogle Scholar
  • 77 Warkentin TE, Margetts P, Connolly SJ, Lamy A, Ricci C, Eikelboom JW. Recombinant factor VIIa (rFVIIa) and hemodialysis to manage massive dabigatran-associated postcardiac surgery bleeding. Blood 2012; 119 (09) 2172-2174
    CrossrefPubMedGoogle Scholar
  • 78 Masotti L, Lorenzini G, Seravalle C. et al. Management of new oral anticoagulants related life threatening or major bleedings in real life: a brief report. J Thromb Thrombolysis 2015; 39 (04) 427-433
    CrossrefPubMedGoogle Scholar
  • 79 Pollack Jr. CV, Reilly PA, van Ryn J. et al. Idarucizumab for dabigatran reversal - full cohort analysis. N Engl J Med 2017; 377 (05) 431-441
    CrossrefPubMedGoogle Scholar
  • 80 Connolly SJ, Milling Jr TJ, Eikelboom JW. et al; ANNEXA-4 Investigators. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med 2016; 375 (12) 1131-1141
    CrossrefPubMedGoogle Scholar
  • 81 Hwang JH, Fisher DA, Ben-Menachem T. et al; Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy. The role of endoscopy in the management of acute non-variceal upper GI bleeding. Gastrointest Endosc 2012; 75 (06) 1132-1138
    CrossrefPubMedGoogle Scholar
  • 82 Chai-Adisaksopha C, Hillis C, Monreal M, Witt DM, Crowther M. Thromboembolic events, recurrent bleeding and mortality after resuming anticoagulant following gastrointestinal bleeding. A meta-analysis. Thromb Haemost 2015; 114 (04) 819-825
    Article in Thieme ConnectPubMedGoogle Scholar
  • 83 Gralnek IM, Dumonceau J-M, Kuipers EJ. et al. Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2015; 47 (10) a1-a46
    Article in Thieme ConnectPubMedGoogle Scholar
  • 84 Reddy VY, Sievert H, Halperin J. et al; PROTECT AF Steering Committee and Investigators. Percutaneous left atrial appendage closure vs warfarin for atrial fibrillation: a randomized clinical trial. JAMA 2014; 312 (19) 1988-1998
    CrossrefPubMedGoogle Scholar
  • 85 Holmes Jr. DR, Kar S, Price MJ. et al. Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial. J Am Coll Cardiol 2014; 64 (01) 1-12
    CrossrefPubMedGoogle Scholar
  • 86 Osmancik P, Herman D, Neuzil P. et al; PRAGUE-17 Trial Investigators. Left atrial appendage closure versus direct oral anticoagulants in high-risk patients with atrial fibrillation. J Am Coll Cardiol 2020; 75 (25) 3122-3135
    CrossrefPubMedGoogle Scholar
  • 87 Majeed A, Hwang H-G, Connolly SJ. et al. Management and outcomes of major bleeding during treatment with dabigatran or warfarin. Circulation 2013; 128 (21) 2325-2332
    CrossrefPubMedGoogle Scholar
  • 88 Werth S, Breslin T, NiAinle F, Beyer-Westendorf J. Bleeding risk, management and outcome in patients receiving non-VKA oral anticoagulants (NOACs). Am J Cardiovasc Drugs 2015; 15 (04) 235-242
    CrossrefPubMedGoogle Scholar
  • 89 Ng DL-C, Gan G-G, Chai C-S. et al. Comparing quality of life and treatment satisfaction between patients on warfarin and direct oral anticoagulants: a cross-sectional study. Patient Prefer Adherence 2019; 13: 1363-1373
    CrossrefPubMedGoogle Scholar
  • 90 Beyer-Westendorf J, Förster K, Pannach S. et al. Rates, management, and outcome of rivaroxaban bleeding in daily care: results from the Dresden NOAC registry. Blood 2014; 124 (06) 955-962
    CrossrefPubMedGoogle Scholar
  • 91 Kepez A, Erdoğan O. Anticoagulation for non-valvular atrial fibrillation: new anticoagulant agents. Anadolu Kardiyol Derg 2013; 13 (04) 379-384
    PubMedGoogle Scholar
  • 92 Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E. The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126 (3, suppl): 204S-233S
    CrossrefPubMedGoogle Scholar
  • 93 Casais P, Meschengieser SS, Sanchez-Luceros A, Lazzari MA. Patients' perceptions regarding oral anticoagulation therapy and its effect on quality of life. Curr Med Res Opin 2005; 21 (07) 1085-1090
    CrossrefPubMedGoogle Scholar
  • 94 Mani H, Lindhoff-Last E. New oral anticoagulants in patients with nonvalvular atrial fibrillation: a review of pharmacokinetics, safety, efficacy, quality of life, and cost effectiveness. Drug Des Devel Ther 2014; 8: 789-798
    CrossrefPubMedGoogle Scholar
  • 95 Ynsaurriaga FA, Peinado RP, Ormaetxe Merodio JM. Atrial fibrillation and quality of life related to disease and treatment: focus on anticoagulation. Future Cardiol 2014; 10 (03) 381-393
    CrossrefPubMedGoogle Scholar
  • 96 Corbi ISA, Dantas RAS, Pelegrino FM, Carvalho AR. Health related quality of life of patients undergoing oral anticoagulation therapy. Rev Lat Am Enfermagem 2011; 19 (04) 865-873
    CrossrefPubMedGoogle Scholar
  • 97 Lancaster TR, Singer DE, Sheehan MA. et al; Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators. The impact of long-term warfarin therapy on quality of life. Evidence from a randomized trial. Arch Intern Med 1991; 151 (10) 1944-1949
    CrossrefPubMedGoogle Scholar
  • 98 Giardini A, Martin MT, Cahir C. et al. Toward appropriate criteria in medication adherence assessment in older persons: position Paper. Aging Clin Exp Res 2016; 28 (03) 371-381
    CrossrefPubMedGoogle Scholar
  • 99 Wilke T, Bauer S, Mueller S, Kohlmann T, Bauersachs R. Patient preferences for oral anticoagulation therapy in atrial fibrillation: a systematic literature review. Patient 2017; 10 (01) 17-37
    CrossrefPubMedGoogle Scholar
  • 100 Bjelland I, Dahl AA, Haug TT, Neckelmann D. The validity of the Hospital Anxiety and Depression Scale. An updated literature review. J Psychosom Res 2002; 52 (02) 69-77
    CrossrefPubMedGoogle Scholar
  • 101 Balcı KG, Balcı MM, Canpolat U. et al. Comparison of health-related quality of life among patients using novel oral anticoagulants or warfarin for non-valvular atrial fibrillation. Anatol J Cardiol 2016; 16 (07) 474-481
    PubMedGoogle Scholar