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Incidence and predictors of severe bleeding during warfarin treatment

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Abstract

Background

Optimal warfarin prescription requires correct, individualized assessment of the warfarin-related bleeding risk, which randomised controlled trials may underestimate . Observational studies have reported a range of bleeding risks that differ 40-fold. This variation may be caused by time trends, variation in bleeding definition and study subject selection. We investigated the incidence of, and risk factors for severe bleeding in un-selected warfarin-treated patients from Sweden.

Methods

Between 2001 and 2005, 40 centres recruited warfarin-naïve patients commencing warfarin therapy and followed them prospectively with continuous registration of clinical data. The primary outcome was severe bleeding, according to the WHO universal definition of severe adverse drug reactions. The influence of potential risk factors was investigated by means of a Cox proportional-hazards model.

Result

A total of 1523 patients contributed 1276 warfarin-exposed patient-years. The incidence of first-time severe bleeding was 2.3 per 100 patient-years (95% confidence interval 1.4 to 3.1). Male sex and use of drugs potentially interacting with warfarin were the only independent risk factors of severe bleeding, with hazard ratios of 2.8 and 2.3, respectively. Age, target International Normalized Ratio (INR), time spent outside target INR range, and warfarin dose requirement were not significantly associated with bleeding risk.

Conclusions

The risk of severe bleeding in a large naturalistic, prospective cohort of first-time warfarin users was lower than reported in some previous reports. Male gender was an independent predictor of severe bleeding as was the receipt of warfarin-interacting medications at the onset of anticoagulation therapy. Further studies are required to evaluate the effect these findings may have on the quality of current risk-benefit analysis involved in warfarin prescription.

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Acknowledgments

Jonatan D. Lindh is supported by the Swedish Foundation for Strategic Research. The project was supported by the Swedish Science Council (Medicine 04496), Nycomed AB, and the Swedish Drugs and Therapeutics Committee of Southwest Stockholm.

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Authors and Affiliations

  1. Division of Clinical Pharmacology, C1-68, Karolinska University Hospital Huddinge, 14186, Stockholm, Sweden

    Jonatan D. Lindh, Lennart Holm & Anders Rane

  2. Department of Medical Sciences, Clinical Pharmacology, Uppsala University, Uppsala, Sweden

    Marja-Liisa Dahl

  3. Division of Cardiovascular Epidemiology, IMM, Karolinska Institutet, Stockholm, Sweden

    Lars Alfredsson

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  1. Jonatan D. Lindh
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  2. Lennart Holm
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  3. Marja-Liisa Dahl
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  4. Lars Alfredsson
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  5. Anders Rane
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Correspondence to Jonatan D. Lindh.

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Lindh, J.D., Holm, L., Dahl, ML. et al. Incidence and predictors of severe bleeding during warfarin treatment. J Thromb Thrombolysis 25, 151–159 (2008). https://doi.org/10.1007/s11239-007-0048-2

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  • DOI: https://doi.org/10.1007/s11239-007-0048-2

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