Download PDF
Semin Thromb Hemost 2017; 43(05): 514-524
DOI: 10.1055/s-0037-1598061
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Scoring Systems for Estimating the Risk of Anticoagulant-Associated Bleeding

Anna L. Parks
1   Department of Medicine, University of California, San Francisco, California
,
Margaret C. Fang
2   Division of Hospital Medicine, University of California, San Francisco, California
› Author Affiliations
Further Information

Publication History

Publication Date:
30 March 2017 (online)

    Permissions and Reprints

Abstract

Anticoagulant medications are frequently used to prevent and treat thromboembolic disease. However, the benefits of anticoagulants must be balanced with a careful assessment of the risk of bleeding complications that can ensue from their use. Several bleeding risk scores are available, including the Outpatient Bleeding Risk Index, HAS-BLED, ATRIA, and HEMORR2HAGES risk assessment tools, and can be used to help estimate patients' risk for bleeding on anticoagulants. These tools vary by their individual risk components and in how they define and weigh clinical factors. However, it is not yet clear how best to integrate bleeding risk tools into clinical practice. Current bleeding risk scores generally have modest predictive ability and limited ability to predict the most devastating complication of anticoagulation, intracranial hemorrhage. In clinical practice, bleeding risk tools should be paired with a formal determination of thrombosis risk, as their results may be most influential for patients at the lower end of thrombosis risk, as well as for highlighting potentially modifiable risk factors for bleeding. Use of bleeding risk scores may assist clinicians and patients in making informed and individualized anticoagulation decisions.

Keywords

anticoagulants - atrial fibrillation - venous thromboembolism - risk prediction - hemorrhage
 

  • References

  • 1 Schulman S, Kearon C. ; 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 non-surgical patients. J Thromb Haemost 2005; 3 (04) 692-694
    CrossrefPubMedGoogle Scholar
  • 2 Mehran R, Rao SV, Bhatt DL. , et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 2011; 123 (23) 2736-2747
    CrossrefPubMedGoogle Scholar
  • 3 Fang MC, Go AS, Chang Y. , et al. Death and disability from warfarin-associated intracranial and extracranial hemorrhages. Am J Med 2007; 120 (08) 700-705
    CrossrefPubMedGoogle Scholar
  • 4 Fang MC, Go AS, Chang Y. , et al. Thirty-day mortality after ischemic stroke and intracranial hemorrhage in patients with atrial fibrillation on and off anticoagulants. Stroke 2012; 43 (07) 1795-1799
    CrossrefPubMedGoogle Scholar
  • 5 You JJ, Singer DE, Howard PA. , et al. Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: e531S-e575S
    CrossrefPubMedGoogle Scholar
  • 6 Schulman S, Beyth RJ, Kearon C, Levine MN. Hemorrhagic complications of anticoagulant and thrombolytic treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest 2008; 133: 257S-298S
    CrossrefPubMedGoogle Scholar
  • 7 Risk Factors for Stroke and Efficacy of Antithrombotic Therapy in Atrial Fibrillation Analysis of Pooled Data From Five Randomized Controlled Trials. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch Intern Med 1994; 154 (13) 1449-1457
    CrossrefPubMedGoogle Scholar
  • 8 van Walraven C, Hart RG, Singer DE. , et al. Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis. JAMA 2002; 288 (19) 2441-2448
    CrossrefPubMedGoogle Scholar
  • 9 Go AS, Hylek EM, Chang Y. , et al. Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice?. JAMA 2003; 290 (20) 2685-2692
    CrossrefPubMedGoogle Scholar
  • 10 Palareti G, Leali N, Coccheri S. , et al; Italian Study on Complications of Oral Anticoagulant Therapy. Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT). Lancet 1996; 348 (9025): 423-428
    CrossrefPubMedGoogle Scholar
  • 11 Hylek EM, Evans-Molina C, Shea C, Henault LE, Regan S. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007; 115 (21) 2689-2696
    CrossrefPubMedGoogle Scholar
  • 12 Ruff CT, Giugliano RP, Braunwald E. , et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014; 383 (9921): 955-962
    CrossrefPubMedGoogle Scholar
  • 13 Linkins L-A, Choi PT, Douketis JD. Clinical impact of bleeding in patients taking oral anticoagulant therapy for venous thromboembolism: a meta-analysis. Ann Intern Med 2003; 139 (11) 893-900
    CrossrefPubMedGoogle Scholar
  • 14 Ruíz-Giménez N, Suárez C, González R. , et al; RIETE Investigators. Predictive variables for major bleeding events in patients presenting with documented acute venous thromboembolism. Findings from the RIETE Registry. Thromb Haemost 2008; 100 (01) 26-31
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 van der Hulle T, Kooiman J, den Exter PL, Dekkers OM, Klok FA, Huisman MV. Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis. J Thromb Haemost 2014; 12 (03) 320-328
    CrossrefPubMedGoogle Scholar
  • 16 Fang MC, Go AS, Hylek EM. , et al. Age and the risk of warfarin-associated hemorrhage: the anticoagulation and risk factors in atrial fibrillation study. J Am Geriatr Soc 2006; 54 (08) 1231-1236
    CrossrefPubMedGoogle Scholar
  • 17 Beyth RJ, Quinn LM, Landefeld CS. Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am J Med 1998; 105 (02) 91-99
    CrossrefPubMedGoogle Scholar
  • 18 Kearon C, Akl EA, Comerota AJ. , et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: e419S-e494S
    CrossrefPubMedGoogle Scholar
  • 19 Rao SV, McCoy LA, Spertus JA. , et al. An updated bleeding model to predict the risk of post-procedure bleeding among patients undergoing percutaneous coronary intervention: a report using an expanded bleeding definition from the National Cardiovascular Data Registry CathPCI Registry. JACC Cardiovasc Interv 2013; 6 (09) 897-904
    CrossrefPubMedGoogle Scholar
  • 20 Mathews R, Peterson ED, Chen AY. , et al. In-hospital major bleeding during ST-elevation and non-ST-elevation myocardial infarction care: derivation and validation of a model from the ACTION Registry®-GWTG™. Am J Cardiol 2011; 107 (08) 1136-1143
    CrossrefPubMedGoogle Scholar
  • 21 Palareti G, Legnani C, Lee A. , et al. A comparison of the safety and efficacy of oral anticoagulation for the treatment of venous thromboembolic disease in patients with or without malignancy. Thromb Haemost 2000; 84 (05) 805-810
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Herman D, Peternel P, Stegnar M, Breskvar K, Dolzan V. The influence of sequence variations in factor VII, gamma-glutamyl carboxylase and vitamin K epoxide reductase complex genes on warfarin dose requirement. Thromb Haemost 2006; 95 (05) 782-787
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Hijazi Z, Oldgren J, Lindbäck J. , et al, on behalf of the ARISTOTLE and RE-LY Investigators. The novel biomarker-based ABC (age, biomarkers, clinical history)-bleeding risk score for patients with atrial fibrillation: a derivation and validation study. Lancet 2016; 387 (10035): 2302-2311
    CrossrefPubMedGoogle Scholar
  • 24 Hart RG, Tonarelli SB, Pearce LA. Avoiding central nervous system bleeding during antithrombotic therapy: recent data and ideas. Stroke 2005; 36 (07) 1588-1593
    CrossrefPubMedGoogle Scholar
  • 25 Gage BF, Birman-Deych E, Kerzner R, Radford MJ, Nilasena DS, Rich MW. Incidence of intracranial hemorrhage in patients with atrial fibrillation who are prone to fall. Am J Med 2005; 118 (06) 612-617
    CrossrefPubMedGoogle Scholar
  • 26 Pugh D, Pugh J, Mead GE. Attitudes of physicians regarding anticoagulation for atrial fibrillation: a systematic review. Age Ageing 2011; 40 (06) 675-683
    CrossrefPubMedGoogle Scholar
  • 27 Donzé J, Clair C, Hug B. , et al. Risk of falls and major bleeds in patients on oral anticoagulation therapy. Am J Med 2012; 125 (08) 773-778
    CrossrefPubMedGoogle Scholar
  • 28 White HD, Gruber M, Feyzi J. , et al. Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V. Arch Intern Med 2007; 167 (03) 239-245
    CrossrefPubMedGoogle Scholar
  • 29 Fang MC, Chang Y, Hylek EM. , et al. Advanced age, anticoagulation intensity, and risk for intracranial hemorrhage among patients taking warfarin for atrial fibrillation. Ann Intern Med 2004; 141 (10) 745-752
    CrossrefPubMedGoogle Scholar
  • 30 Powell JR. Are new oral anticoagulant dosing recommendations optimal for all patients?. JAMA 2015; 313 (10) 1013-1014
    CrossrefPubMedGoogle Scholar
  • 31 Quinn GR, Singer DE, Chang Y. , et al. Effect of selective serotonin reuptake inhibitors on bleeding risk in patients with atrial fibrillation taking warfarin. Am J Cardiol 2014; 114 (04) 583-586
    CrossrefPubMedGoogle Scholar
  • 32 Baillargeon J, Holmes HM, Lin YL, Raji MA, Sharma G, Kuo YF. Concurrent use of warfarin and antibiotics and the risk of bleeding in older adults. Am J Med 2012; 125 (02) 183-189
    CrossrefPubMedGoogle Scholar
  • 33 Davidson BL, Verheijen S, Lensing AW. , 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
  • 34 Lamberts M, Olesen JB, Ruwald MH. , et al. Bleeding after initiation of multiple antithrombotic drugs, including triple therapy, in atrial fibrillation patients following myocardial infarction and coronary intervention: a nationwide cohort study. Circulation 2012; 126 (10) 1185-1193
    CrossrefPubMedGoogle Scholar
  • 35 Bungard TJ, Ghali WA, Teo KK, McAlister FA, Tsuyuki RT. Why do patients with atrial fibrillation not receive warfarin?. Arch Intern Med 2000; 160 (01) 41-46
    CrossrefPubMedGoogle Scholar
  • 36 Fang MC, Stafford RS, Ruskin JN, Singer DE. National trends in antiarrhythmic and antithrombotic medication use in atrial fibrillation. Arch Intern Med 2004; 164 (01) 55-60
    CrossrefPubMedGoogle Scholar
  • 37 Moons KG, Altman DG, Reitsma JB. , et al. Transparent reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD): explanation and elaboration. Ann Intern Med 2015; 162 (01) W1-73
    PubMedGoogle Scholar
  • 38 Steyerberg EW, Vickers AJ, Cook NR. , et al. Assessing the performance of prediction models: a framework for traditional and novel measures. Epidemiology 2010; 21 (01) 128-138
    CrossrefPubMedGoogle Scholar
  • 39 Proietti M, Senoo K, Lane DA, Lip GY. Major bleeding in patients with non-valvular atrial fibrillation: impact of time in therapeutic range on contemporary bleeding risk scores. Sci Rep 2016; 6: 24376
    CrossrefPubMedGoogle Scholar
  • 40 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
  • 41 Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. 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
  • 42 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
  • 43 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
  • 44 Nieto JA, Solano R, Ruiz-Ribó MD. , et al; Riete Investigators. Fatal bleeding in patients receiving anticoagulant therapy for venous thromboembolism: findings from the RIETE registry. J Thromb Haemost 2010; 8 (06) 1216-1222
    CrossrefPubMedGoogle Scholar
  • 45 Nieto JA, Solano R, Trapero Iglesias N. , et al; RIETE Investigators. Validation of a score for predicting fatal bleeding in patients receiving anticoagulation for venous thromboembolism. Thromb Res 2013; 132 (02) 175-179
    CrossrefPubMedGoogle Scholar
  • 46 Kearon C, Akl EA, Ornelas J. , et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 2016; 149 (02) 315-352
    CrossrefPubMedGoogle Scholar
  • 47 Hippisley-Cox J, Coupland C. Predicting risk of upper gastrointestinal bleed and intracranial bleed with anticoagulants: cohort study to derive and validate the QBleed scores. BMJ 2014; 349: g4606
    CrossrefPubMedGoogle Scholar
  • 48 Roldán V, Marín F, Fernández H. , et al. Predictive value of the HAS-BLED and ATRIA bleeding scores for the risk of serious bleeding in a “real-world” population with atrial fibrillation receiving anticoagulant therapy. Chest 2013; 143 (01) 179-184
    CrossrefPubMedGoogle Scholar
  • 49 Lopes RD. et al. Stroke prevention in atrial fibrillation. Comparative effectiveness review no. 123 (Prepared by the Duke evidence-based practice center under contract no. 290–2007–10066-I) AHRQ Publication no. 13–EHC113-EF: Rockville MD. Agency for Healthcare Research and Quality August 2013
    PubMedGoogle Scholar
  • 50 Skanes AC, Healey JS, Cairns JA. , et al; Canadian Cardiovascular Society Atrial Fibrillation Guidelines Committee. Focused 2012 update of the Canadian Cardiovascular Society atrial fibrillation guidelines: recommendations for stroke prevention and rate/rhythm control. Can J Cardiol 2012; 28 (02) 125-136
    CrossrefPubMedGoogle Scholar
  • 51 Camm AJ, Lip GY, De Caterina R. , et al; ESC Committee for Practice Guidelines (CPG). 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 2012; 33 (21) 2719-2747
    CrossrefPubMedGoogle Scholar
  • 52 Burgess S, Crown N, Louzada ML, Dresser G, Kim RB, Lazo-Langner A. Clinical performance of bleeding risk scores for predicting major and clinically relevant non-major bleeding events in patients receiving warfarin. J Thromb Haemost 2013; 11 (09) 1647-1654
    CrossrefPubMedGoogle Scholar
  • 53 Zhu W, He W, Guo L, Wang X, Hong K. The HAS-BLED score for predicting major bleeding risk in anticoagulated patients with atrial fibrillation: A systematic review and meta-analysis. Clin Cardiol 2015; 38 (09) 555-561
    CrossrefPubMedGoogle Scholar
  • 54 Senoo K, Proietti M, Lane DA, Lip GYH. Evaluation of the HAS-BLED, ATRIA and ORBIT bleeding risk scores in atrial fibrillation patients on warfarin. Am J Med 2016; 129 (06) 600-607
    CrossrefPubMedGoogle Scholar
  • 55 Friberg L, Rosenqvist M, Lip GY. 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
  • 56 Riva N, Bellesini M, Di Minno MN. , et al. Poor predictive value of contemporary bleeding risk scores during long-term treatment of venous thromboembolism. A multicentre retrospective cohort study. Thromb Haemost 2014; 112 (03) 511-521
    Article in Thieme ConnectPubMedGoogle Scholar
  • 57 Scherz N, Méan M, Limacher A. , et al. Prospective, multicenter validation of prediction scores for major bleeding in elderly patients with venous thromboembolism. J Thromb Haemost 2013; 11 (03) 435-443
    CrossrefPubMedGoogle Scholar
  • 58 MacLean S, Mulla S, Akl EA. , et al. Patient values and preferences in decision making for antithrombotic therapy: a systematic review: antithrombotic therapy and prevention of thrombosis, 9th edition: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; (141) e1S-e23S
    PubMedGoogle Scholar
  • 59 O'Brien EC, Kim S, Hess PL. , et al. Effect of the 2014 atrial fibrillation guideline revisions on the proportion of patients recommended for oral anticoagulation. JAMA Intern Med 2015; 175 (05) 848-850
    CrossrefPubMedGoogle Scholar
  • 60 Eckman MH, Wise RE, Naylor K. , et al. Developing an Atrial Fibrillation Guideline Support Tool (AFGuST) for shared decision making. Curr Med Res Opin 2015; 31 (04) 603-614
    CrossrefPubMedGoogle Scholar
  • 61 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
  • 62 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
  • 63 Granger CB, Alexander JH, McMurray JJ. , 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
  • 64 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
  • 65 Lauffenburger JC, Farley JF, Gehi AK, Rhoney DH, Brookhart MA, Fang G. Effectiveness and safety of dabigatran and warfarin in real-world US patients with non-valvular atrial fibrillation: a retrospective cohort study. J Am Heart Assoc 2015; 4 (04) 4
    PubMedGoogle Scholar
  • 66 Graham DJ, Reichman ME, Wernecke M. , et al. Cardiovascular, bleeding, and mortality risks in elderly Medicare patients treated with dabigatran or warfarin for nonvalvular atrial fibrillation. Circulation 2015; 131 (02) 157-164
    CrossrefPubMedGoogle Scholar
  • 67 Hernandez I, Zhang Y. Risk of bleeding with dabigatran in 2010-2011 Medicare data. JAMA Intern Med 2015; 175 (07) 1245-1247
    PubMedGoogle Scholar
  • 68 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
  • 69 Chang HY, 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
  • 70 Laliberté F, Cloutier M, Nelson WW. , et al. Real-world comparative effectiveness and safety of rivaroxaban and warfarin in nonvalvular atrial fibrillation patients. Curr Med Res Opin 2014; 30 (07) 1317-1325
    CrossrefPubMedGoogle Scholar