Warfarin Re-initiation Gone Awry: A Case of Inadvertent Overdose Mandating Critical INR Management

W arfarin is a commonly used anticoagulant for the primary or secondary prevention of thrombotic events. 1 Tremendous inter-individual variability in warfarin dosing is apparent, necessitating frequent monitoring via the international normalized ratio (INR).The most feared complication of warfarin therapy is major bleeding, and the risk of this problem increases when the INR exceeds 4.0. 2 Critical INR values (defined in the Edmonton region of Alberta Health Services as an INR > 5.0; the definition may vary by jurisdiction) are reported urgently to clinicians to enable prompt patient management.For ambulatory patients who are not bleeding, strategies to manage critical INRs include withholding warfarin therapy, with the option of administering oral vitamin K 1 , but guidelines vary and have changed over time (Table 1).1,3,4 It is common for patients who are taking warfarin to have their therapy interrupted, for example, when they undergo invasive procedures.For patients at higher risk of thrombosis, low-molecular-weight heparin (LMWH) is commonly prescribed during both the washout period for warfarin (before the procedure) and the build-up period for warfarin (after the procedure).5 The duration of postprocedure LMWH depends on the time it takes for the patient's INR to reach a therapeutic level.Clinicians typically restart warfarin at the patient's prior maintenance dose, 6,7 although in a previous study, we found that it took a median of 20.5 days at the prior maintenance dose to reach a therapeutic INR 8 ; prolonged LMWH therapy is needed during this time.Reported here is a case of warfarin re-initiation, in which the clinic's usual strategy, based on prior maintenance dosing, resulted in inadvertent warfarin overdose requiring management of a critical INR.For both of these aspects of warfarin management (re-initiation of warfarin and management of critical INR), the literature is reviewed and applied to this case, with emphasis on practical management issues. CASE REPORTA 25-year-old woman who was referred to the Anticoagulation Management Service at the University of Alberta Hospital in November 2008 had been taking warfarin (INR range 2.0-3.0)since having a saddle pulmonary embolism in July 2007.*Her previous medical history included antithrombin III deficiency, protein C deficiency, factor V Leiden mutation, and a family history of thrombophilia.She was not taking any other medications.Under the care of the Anticoagulation Management Service, her INR was maintained within the therapeutic range with a total weekly dose of warfarin 86 to 91 mg.She was adherent with warfarin therapy and reported missing 1 or 2 doses per year.She indicated a desire to become pregnant, with plans to try to conceive in early 2012.In collaboration with the Obstetric Medicine Clinic, the clinic instructed her to continue taking warfarin while attempting to become pregnant and to perform pregnancy tests every 1 to 2 weeks.In May 2012, she reported a positive result on a pregnancy test, and it was determined that she was at 4 weeks' gestation.She was instructed to discontinue the warfarin, and enoxaparin 80 mg subcutaneously every 12 h was prescribed (serum creatinine 61 µmol/L in October 2011, weight 78 kg in May 2012).Throughout her pregnancy, the LMWH therapy was managed by the Obstetric Medicine Clinic.The patient gave birth on January 17, 2013, and the Anticoagulation Management Service became involved in her care again, for re-initiation of warfarin on February 1 (Figure 1).At that time, she was continuing to self-administer enoxaparin 80 mg subcutaneously every 12 h (weight 77 kg in February 2013).

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