Clinical predictors of prolonged delay in return of the international normalized ratio to within the therapeutic range after excessive anticoagulation with warfarin

Background: An elevated international normalized ratio (INR) increases the risk for major hemorrhage during warfarin therapy. Optimal management of pa tients with asymptomatic elevations in INR is hampered by the lack of under standing of the time course of INR decay after cessation of warfarin therap y. Objective: To identify predictors of the rate of INR normalization after ex cessive anticoagulation. Design: Retrospective cohort study. Setting: Outpatient anticoagulant therapy unit. Patients: Outpatients with an INR greater than 6.0 were identified from Aug ust 1993 to September 1998. Patients in whom two doses of warfarin were wit hheld and a follow-up INR was obtained on the second calendar day were enro lled. No patient received vitamin K-tau. Measurements: The INR was measured 2 days after an INR greater than 6.0 was recorded. Results: Of 633 study patients with an initial INR greater than 6.0, 232 (3 7%) still had an INR of 4.0 or greater after two doses of warfarin were wit hheld. Patients who required larger weekly maintenance doses of warfarin we re less likely to have an INR of 4.0 or greater on day 2 (adjusted odds rat io per 10 mg of warfarin, 0.87 [95% Cl, 0.79 to 0.97]). Other risk factors for having an INR of 4.0 or greater on day 2 included age (odds ratio per d ecade of life, 1.18 [Cl, 1.01 to 1.38]), index INR (odds ratio per unit, 1. 25 [Cl, 1.14 to 1.37]), decompensated congestive heart failure (odds ratio, 2.79 [Cl, 1.30 to 5.98]), and active cancer (odds ratio, 2.48 [Cl, 1.11 to 5.57]). Conclusions: Steady-state warfarin dose, advanced age, and extreme elevatio n in INR are risk factors for prolonged delay in return of the INR to withi n the therapeutic range. Decompensated congestive heart failure and active cancer greatly increase this risk.