Treatment of Excessive Anticoagulation With Phytonadione (Vitamin K)

Abstract

Background: : Patients taking oral anticoagulants with an international normalized ratio (INR) greater than 4.0 are at increased risk for bleeding. We performed a metaanalysis to determine the effectiveness of phytonadione (vitamin K) in treating excessive anticoagulation. Methods:The MEDLINE, EMBASE, and Cochrane Library databases were searched (without language restrictions) for articles published between January 1985 and September 2004. Randomized controlled trials or prospective, nonrandomized trials that used vitamin K to treat patients without major hemorrhage with an INR greater than 4.0 due to oral anticoagulant use were included. The primary outcome was achievement of the target INR (1.8-4.0) at 24 hours after vitamin K administration. Summary estimates were calculated using a random effects model.Results: Twenty-one studies (10 randomized and 11 prospective trials) were included. Among oral vitamin K treatment arms (4, n = 75), the proportion with a target INR at 24 hours was 82% (95% confidence interval [CI], 70%-93%), which was similar to intravenous vitamin K treatment arms (6, n = 69; target INR, 77%; 95% CI, 60%-95%). Treatment arms of subcutaneous vitamin K (3, n=58; 31%; 95% CI, 7%-55%) and placebo/observation (2, n = 27; 20%; 95% CI, 0%-47%) were less likely to achieve target INR at 24 hours. Only 1 of 21 trials appropriately assessed for adverse events, so a summary estimate for bleeding risk could not be generated.Conclusions: Limited evidence suggests that oral and intravenous vitamin K are equivalent and more effective for excessive anticoagulation than simply withholding warfarin sodium. Subcutaneous vitamin K, however, is inferior to oral and intravenous vitamin K for this indication and is similar to placebo. Whether treatment with vitamin K decreases hemorrhagic events cannot be determined from the published literature.

Vitamin K Dosing to Reverse Warfarin Based on INR, Route of Administration, and Home Warfarin Dose in the Acute/Critical Care Setting

“…9,10 A meta-analysis of vitamin K studies found that oral and intravenous vitamin K-treated patients achieved similar rates of target INR at 24 hours (82% vs 77%), but oral vitamin K resulted in a higher frequency of INR overcorrection (INR <1.5). 11 In our study, there was no difference between the intravenous and oral groups in bridging incidence or duration. Although there was a significantly higher duration of hospital stay in the intravenous group, the cause was unclear.…”

Urgent reversal of vitamin K antagonists

“…The reversal of vitamin K antagonists can be monitored with the INR, which is very sensitive to factor VII levels. A recent meta-analysis of 21 studies (n=983) suggested that oral and intravenous vitamin K had similar efficacy, but that subcutaneous vitamin K was inferior and similar to placebo 14. In the four trials using oral vitamin K (n=75), the proportion of patients with a target INR at 24 hours was 82% (95% confidence interval 70% to 93%), which was similar to that with intravenous vitamin K (six trials, n=69; target INR 77%, 95% CI 60% to 95%) 14…”

Adherence to guidelines for the management of excessive warfarin anticoagulation

“…High doses of vitamin K1 can predispose to warfarin resistance for a week or more, rendering the patient at risk for thrombotic events [7]. Oral administration is more rapid, predictably effective, safer, and more convenient than administration by subcutaneous (SQ) and intramuscular (IM) routes [8][9][10][11][12][13][14]. When there is a greater urgency to reverse anticoagulation, Vitamin K1 can be administered by slow intravenous (IV) infusion [8,15,16].…”

“…When there is a greater urgency to reverse anticoagulation, Vitamin K1 can be administered by slow intravenous (IV) infusion [8,15,16]. Vitamin K1 administered by the oral or IV routes lower INRs equivalently at 24 h [11,16].…”