Failure to correct International Normalized Ratio and mortality among patients with warfarin-related major bleeding: An analysis of electronic health records

Abstract

Background: Delayed correction of blood clotting times as measured by the International Normalized Ratio (INR) is associated with adverse outcomes among certain patients with warfarin-related major bleeding. However, there are limited data on the association between INR correction and mortality.Objective: To assess factors associated with 30-day mortality and time to death in patients receiving fresh frozen plasma (FFP) for warfarin-associated major bleeding. Methods: A retrospective database analysis was undertaken with electronic health record data from a large integrated health system. Patients met the following criteria: major hemorrhage diagnosis; INR≥2 on the day before or day of receipt of FFP; and prescription fill for warfarin within 90 days. INR correction (defined as INR≤1.3) was evaluated at the last available test 1 day following the start of FFP administration. Kaplan-Meier curves and Cox proportional hazards models were constructed to assess mortality. Results: Four hundred and five patients met the selection criteria (mean age of 75 years, 54% male), and 67% remained uncorrected at 1 day following the start of FFP administration. Among all patients, 11% died within 30 days of hospital admission. An uncorrected INR was not associated with a higher risk of 30-day mortality for patients overall, but was statistically significant for the subgroup with intracranial hemorrhage (ICH) (adjusted odds ratio 2.55; 95% confidence interval 1.04-6.28). Conclusions: Among the subgroup of major bleeding patients with warfarin-associated ICH, those not correcting to either INR≤1.3 or INR≤1.5 with the use of FFP have an increased rate of mortality at 30 days. © 2012 International Society on Thrombosis and Haemostasis.