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DOI: 10.1160/TH07-04-0297
The risk of bleeding with warfarin: A systematic review and performance analysis of clinical prediction rules
Publication History
Received
23 April 2007
Accepted after resubmission
15 August 2007
Publication Date:
30 November 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/200705/lookinside/thumbnails/10-1160-th07-04-0297-1.jpg)
Summary
It was the objective of this article to qualitatively review and evaluate the clinical prediction rules (CPRs) available for estimating bleeding risk in patients commencing warfarin therapy. A systematic review of PubMed (1949 to December 2006), MEDLINE (1966 to December 2006); EMBASE (1980 to December 2006), Cochrane Database of Systematic Reviews (to December 2006), and International Pharmaceutical Abstracts (1970 to Demember 2006) was conducted. Seven studies were found that detailed CPRs used to assess risk of bleeding prior to commencing warfarin therapy. Four studies described distinct CPRs. The remaining three studies were further validations of one of the CPRs, the Outpatient Bleeding Risk Index. The Outpatient Bleeding Risk Index was classified as being of Level 2 evidence while the remaining three indices were classified as being of Level 4 evidence. In no case did the CPRs exhibit performance characteristics that would indicate“strong” ability to predict the presence of absence of major bleeding among warfarin recipients. The modified Outpatient Bleeding Risk Index exhibited moderate predictive ability for major bleeding in two studies, although pooling of all studies of this CPR did not reveal moderate or better performance. None of the CPRs identified “any bleeding” with moderate or strong predictive ability. None of the available CPRs exhibit sufficient predictive accuracy or have trials evaluating the impact of their use on patient outcomes. Hence, no existing CPR can be recommended for widespread use in practice at present.
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References
- 1 Ansell J, Hirsh J, Poller L. et al. The pharmacology and management of the vitamin K antagonists: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126 (Suppl. 03) 204S-233S.
- 2 Landefeld CS, Beyth RJ. Anticoagulant-related bleeding: Clinical epidemiology, prediction, and prevention. Am J Med 1993; 95: 315-328.
- 3 Gasse C, Hollowell J, Meier CR. et al. Drug interactions and risk of acute bleeding leading to hospitalisation or death in patients with chronic atrial fibrillation treated with warfarin. Thromb Haemost 2005; 94: 537-543.
- 4 The Cochrane Library.. Cochrane Reviewers’ Handbook 4.2.2. 2003; Available at: http://www.cochrane dk/cochrane/handbook/hbook.htm Accessed May 18, 2005.
- 5 The TIMI Study Group. The TIMI Study Group.. 2003; Available at: http://www.timi.org Accessed April 9, 2007.
- 6 Levine MN, Raskob G, Beyth RJ. et al. Hemorrhagic complications of anticoagulant treatment: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126 (Suppl. 03) 287S-310S.
- 7 Ingui BJ, Rogers MAM. Searching for clinical prediction rules in Medline. J Am Med Inform Assoc 2001; 8: 391-397.
- 8 Laupacis A, Sekar N, Stiell IG. Clinical prediction rules: A review and suggested modifications of methodological standards. J Am Med Assoc 1997; 277: 488-494.
- 9 McGinn TG, Guyatt GH, Wyer PC. et al. Users’ guides to the medical literature XXII: How to use articles about clinical decision rules. J Am Med Assoc 2000; 284: 79-84.
- 10 Peirce JC, Cornell RG. Integrating stratum-specific likelihood ratios with the analysis of ROC curves. Med Decis Making 1993; 13: 141-151.
- 11 Deeks JJ, Altman DG. Diagnostic tests 4: likelihood ratios. Br Med J 2004; 329: 168-169.
- 12 Jaeschke R, Guyatt G, Sackett DL. Users’ guides to the medical literature. III. How to use an article about a diagnostic test. A. Are the results of the study valid? Evidence-Based Medicine Working Group. J Am Med Assoc 1994; 271: 389-391.
- 13 Jaeschke R, Guyatt GH, Sackett DL. User’s guides to the medical literature: III. How to use an article about a diagnostic test: B. What are the results and will they help me in caring for my patients? J Am Med Assoc 1994; 271: 703-707.
- 14 Van der Meer FJM, Rosendaal FR, Vandenbroucke JP. et al. Assessment of a bleeding risk index in two cohorts of patients treated with oral anticoagulants. Thromb Haemost 1996; 76: 12-16.
- 15 Landefeld CS, Cook EF, Flatley M. et al. Identification and preliminary validation of predictors of major bleeding in hospitalized patients starting anticoagulant therapy. Am J Med 1987; 82: 703-713.
- 16 Landefeld CS, McGuire III E, Rosenblatt MW. A bleeding risk index for estimating the probability of major bleeding in hospitalized patients starting anticoagulant therapy. Am J Med 1990; 89: 569-578.
- 17 Landefeld CS, Goldman L. Major bleeding in outpatients treated with warfarin: Incidence and prediction by factors known at the start of outpatient therapy. Am J Med 1989; 87: 144-152.
- 18 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: 91-99.
- 19 Wells PS, Forgie MA, Simms M. et al. The Outpatient Bleeding Risk Index: Validation of a tool for predicting bleeding rates in patients treated for deep venous thrombosis and pulmonary embolism. Arch Intern Med 2003; 163: 917-920.
- 20 Aspinall SL, DeSanzo BE, Trilli LE. et al. Bleeding risk index in an anticoagulation clinic: Assessment by indication and implications for care. J Gen Intern Med 2005; 20: 1008-1013.
- 21 Kuijer PMM, Hutten BA, Prins MH. et al. Prediction of the risk of bleeding during anticoagulant treatment for venous thromboembolism. Arch Intern Med 1999; 159: 457-460.
- 22 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: 713-719.
- 23 Shireman TI, Mahnken JD, Howard PA. et al. Development of a contemporary bleeding risk model for elderly warfarin recipients. Chest 2006; 130: 1390-1396.
- 24 Kearon C, Ginsberg JS, Kovacs MJ. et al. Comparison of low-intensity warfarin therapy with conventional- intensity warfarin therapy for long-term prevention of recurrent venous thromboembolism. N Engl J Med 2003; 349: 631-639.
- 25 Waldo AL, Becker RC, Tapson VF. et al. Hospitalized patients with atrial fibrillation and a high risk of stroke are not being provided with adequate anticoagulation. J Am Coll Cardiol 2005; 46: 1729-1736.
- 26 Bungard TJ, Ghali WA, Teo KK. et al. Why do patients with atrial fibrillation not receive warfarin?. Arch Intern Med 2000; 160: 41-46.
- 27 Choudhry NK, Soumerai SB, Normand SL. et al. Warfarin prescribing in atrial fibrillation: the impact of physician, patient, and hospital characteristics. Am J Med 2006; 119: 607-615.
- 28 McCrory DC, Matchar DB, Samsa G. et al. Physician attitudes about anticoagulation for nonvalvular atrial fibrillation in the elderly. Arch Intern Med 1995; 155: 277-281.