Warfarin anticoagulation in hemodialysis patients: A systematic review of bleeding

Background: Despite common use of warfarin, the bleeding risk associated with this treatment in hemodialysis (HD) patients is unknown. Study Design: Systematic review. Selection Criteria for Studies: Inclusion criteria were case series, cohort studies, and randomized controlled trials in dialysis patients that examined the bleeding risk associated with warfarin use compared with no warfarin or subcutaneous heparin. Studies with fewer than 10 subjects, case reports, abstracts lacking complete data sets, review articles, and editorials were excluded. Predictor: Warfarin use compared with no warfarin or subcutaneous heparin. Outcomes: Data for bleeding were reported as rates: number of bleeding episodes per number of patient-years of warfarin exposure or follow-up. Results: Of 79 articles and abstracts, 5 met inclusion criteria and 3 more could be added after investigators provided additional information. All studies were of HD patients, and 7 of 8 evaluated the use of warfarin for the prevention of HD access thrombosis. Intensity of anticoagulation varied. Meta-analysis was not possible because of study heterogeneity. Studies of full-intensity anticoagulation and the 1 randomized controlled trial of low-intensity anticoagulation showed major bleeding episode rates ranging from 0.1 to 0.54 events/patient-year of warfarin exposure. These rates are approximately twice as high as those of HD patients receiving either no warfarin or subcutaneous heparin. Limitations: This review is based largely on data from observational studies in which bleeding rates may be confounded by comorbidity. Relatively small sample sizes may provide imprecise estimates of rates. Conclusion: Low- and full-intensity anticoagulation use in HD patients is associated with a significant bleeding risk, which has to be balanced against any potential benefit of therapy. This has to be considered carefully when prescribing warfarin to HD patients.