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  • Open Access

Failure to correct the international normalized ratio in patients with anticoagulant-related major bleeding is associated with increased 90-day mortality

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Critical Care201115 (Suppl 1) :P432

  • Published:


  • Sensitivity Analysis
  • Warfarin
  • Adverse Outcome
  • Mortality Risk
  • International Normalize Ratio


Supratherapeutic international normalized ratio (INR) levels have been shown to be a significant predictor of death among patients with anticoagulant-related (ACR) intracranial hemorrhage (ICH). We assessed factors associated with 90-day mortality and time to death in patients receiving fresh frozen plasma (FFP) for ACR major bleeding in clinical practice.


A retrospective analysis was undertaken using electronic medical records from an integrated system. Patients who received FFP between 1 January 2004 and 31 December 2010, and who met the following criteria were selected: major hemorrhage diagnosis the day before to the day after initial FFP administration; INR ≥2 on the day before or the day of FFP and another INR result up to 1 day after FFP; and warfarin supply within 90 days prior to hospitalization. INR correction (defined as INR ≤1.3) was evaluated at the last available test up to 1 day following FFP start. Patients dying within 72 hours surrounding FFP were excluded. Kaplan-Meier survival curves were estimated and time to death was assessed using Cox proportional hazards models. In sensitivity analysis, an INR threshold ≤1.5 was used to account for clinical practices that aim to avoid adverse outcomes (for example, thrombosis) of certain co-morbidities.


A total of 405 patients met the selection criteria (mean age 75 years, 53% male), and 67% remained uncorrected. Overall, 19% of patients died within 90 days of hospital admission, with a higher proportion of uncorrected versus corrected patients dying (24% vs. 13%, P = 0.013). In Cox regression analysis, patients with a first elevated INR value >4 (HR = 2.21; 95% CI = 1.36 to 3.60), with an ICH bleed versus gastrointestinal or other bleed (HR = 2.08; 95% CI = 1.27 to 3.40), and with uncorrected INR (HR = 2.33; 95% CI = 1.30 to 4.16) were significantly more likely to die within 90 days of admission. In a sensitivity analysis (correction defined as INR ≤1.5), 39% remained uncorrected within 24 hours of FFP administration, with factors predicting 90-day mortality remaining robust in regression analysis.


Among ACR major bleed patients, not correcting to either INR ≤1.3 or INR ≤1.5 with FFP is associated with an increased rate of mortality at 90 days. Further assessment of co-morbidities associated with hemostasis and other predictors of mortality risk in this population is warranted.

Authors’ Affiliations

Boston Health Economics, Waltham, MA, USA
CSL Behring, King of Prussia, PA, USA


© Menzin et al. 2011

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.