Comparing Different Routes and Doses of Phytonadione for Reversing Excessive Anticoagulation

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Abstract
ORAL ANTICOAGULATION is used widely for treatment and prevention of thromboembolic events, and bleeding is its most significant adverse effect. Several recent studies have shown that the risk for major hemorrhage can be reduced dramatically if the prothrombin time (expressed as the international normalized ratio [INR]) is kept below 5.0.1-3 If the patient's INR exceeds 6.0, the American College of Chest Physicians (ACCP) Consensus Conference on Antithrombotic Therapy recommends that reversal using phytonadione (vitamin K1) be considered (Table 1).4 The ACCP recommendations appear to favor subcutaneous (SC) administration of phytonadione, with the intravenous (IV) route being reserved for more severe cases or when poor absorption may be anticipated in patients with "peripheral circulatory failure." The recommendations further indicate that a significant reduction in the INR can be anticipated within 6 to 8 hours. Intravenous phytonadione administration is probably not encouraged because, in rare instances, it causes a severe allergic reaction. A careful literature search, however, failed to identify data on the use of SC administration of phytonadione for reversing the effects of warfarin sodium. Although the ACCP recommendations do not endorse the oral (PO) administration of phytonadione, a few reports have found this route to be effective. Pederson et al5 evaluated the effect of different amounts of vitamin K1 ingested in the diet, while Pengo et al6 and Weibert et al7 examined the effectiveness of 2.5 mg of PO phytonadione. Pengo et al found that the administration of phytonadione corrected the INR to less than 5.0 at 24 hours more effectively than did simply withholding the warfarin dose.6 More recently, Weibert et al reported that 2.5 mg of PO phytonadione reversed excessive anticoagulation in almost all patients within 24 or 48 hours and induced only limited overcorrection in a few patients.