Clinical manifestations and outcomes of severe warfarin overanticoagulation: from the EWA study

Abstract

Introduction: Severe warfarin overanticoagulation is a risk factor for bleeding, but there is little information on its manifestations, prognosis and factors affecting the outcome. We describe the manifestations and clinical outcomes of severe warfarin overanticoagulation in a large group of patients with atrial fibrillation (AF).

Material and methods: All international normalized ratio (INR) samples (n = 961,431) in the Turku University Hospital region between 2003 and 2015 were screened. A total of 412 AF patients with INR ≥9 were compared to 405 patients with stable warfarin anticoagulation for AF. Electronic patient records were manually reviewed to collect comprehensive data.

Results: Of the 412 patients with INR ≥9, bleeding was the primary manifestation in 105 (25.5%). Non-bleeding symptoms were recorded in 165 (40.0%) patients and 142 (34.5%) had no symptoms. A total of 17 (16.2%) patients with a bleed and 67 (21.8%) without bleeding died within 30 days after the event. Intracranial haemorrhage strongly predicted death within 30 days. Other significant predictors were non-bleeding symptoms, active malignancies, recent bleed, history of myocardial infarction, older age, renal dysfunction and a recent treatment episode.

Conclusions: Bleeds are not the major determinant of the poor prognosis in severe overanticoagulation, as coincidental INR ≥9 findings also associate with high mortality.

KEY MESSAGES

• Only a quarter of AF patients with INR ≥9 suffered a bleeding event and the clinical manifestation of INR ≥9 had a significant impact on patient outcome.

• The 30-day mortality rate in patients with INR ≥9 was high ranging from 9.2 to 32.7%.

• Several significant predictors of 30-day mortality after INR ≥9 were identified.

Keywords:

• Atrial fibrillation
• anticoagulation
• bleed
• complication
• warfarin

Acknowledgements

We thank our study coordinator Tuija Vasankari, RN, for her crucial input in study management and Ari Törmä, M.Sc., for providing laboratory data for the study, and Henri Sallinen, BM, Marianne Mäkäräinen, BM, and Melina Issakoff, BM, for the help in the collection of the data. We also thank Ville Langen, MD, for helping with the figure.

Disclosure statement

S.J.: received research grants from the Finnish Foundation for Cardiovascular Research; Clinical Research Fund (EVO) of Turku University Hospital, Turku, Finland, Finnish Cardiac Society. I.N.: None. T.O.K.: Lectures for Bayer, Boehringer Ingelheim, Bristol-Myers-Squibb-Pfizer, Medicines Company, MSD, Astra Zeneca and St Jude Medical, received research grants from the Finnish Medical Foundation, the Finnish Foundation for Cardiovascular Research; Clinical Research Fund (EVO) of Turku University Hospital, Turku, Finland, Finnish Cardiac Society, and an unrestricted grant from Bristol-Myers-Squibb-Pfizer. Member of advisory board for Boehringer-Ingelheim; MSD. R.V.: None. A.V.: None. K.E.J.A.: research grants from the Finnish Foundation for Cardiovascular Research, Clinical Research Fund (EVO) of Turku University Hospital, Turku, Finland; Lectures for Bayer, Cardiome and Boehringer Ingelheim, Member in the advisory boards for Bayer, Astra Zeneca, Bristol-Myers-Squibb-Pfizer.

Additional information

Funding

This study was funded by the Finnish Foundation for Cardiovascular Research, Helsinki, Finland, and State Clinical Research Fund (EVO) of Turku University Hospital, Turku, Finland and the Finnish Medical Foundation, Helsinki, Finland.