An Evaluation of Intravenous Vitamin K for Warfarin Reversal: Are Guideline Recommendations Being Followed?

Abstract

Background: Vitamin K antagonists (eg, warfarin) remain the mainstay of anticoagulation therapy in the United States, with over 22 million prescriptions being filled annually. Unfortunately, warfarin therapy is difficult to manage and increases bleeding risk. The 2012 American College of Chest Physicians guidelines created a warfarin reversal algorithm that suggested the stringent use of intravenous vitamin K. Objective: The purpose of this evaluation was to determine the rates of adherence with guideline recommendations in clinical practice. Method: A convenience sample of 3 months of intravenous vitamin K medication administration data (September to November 2013) was obtained to conduct a retrospective review. Patients with underlying hepatic dysfunction or lack of warfarin therapy were excluded. Vitamin K use was evaluated for consistency with the 2012 guidelines. Results: A total of 364 patients were reviewed and 119 were included. Vitamin K utilization was consistent with guideline recommendations for a total of 30 (25.2%) patients. The most common site of active bleeding requiring reversal was head bleeds, consisting of 56.6% of bleeds. A single dose of 10 mg of vitamin K was the most frequently used dosing strategy. Fresh frozen plasma (73.3%) and four-factor prothrombin complex concentrate (36.7%) were the most commonly used factor products. Conclusion: This evaluation demonstrates that there is a difference between clinical judgment and guideline adherence. True adherence with the guidelines may not be necessary; however, there is room for improvement in both the appropriateness and safety of intravenous vitamin K use. 1 The volume of prescriptions is most likely driven by the familiarity with the long-standing product, comfort with the approach to reversal, and the wide array of US Food and Drug Administration (FDA)-approved indications, including cardiac valve replacement, prevention and/or treatment of venous thromboembolism, and prevention and/or treatment of thromboembolic complications associated with atrial fibrillation. Vitamin K antagonists achieve their anticoagulant effects through the inhibition of vitamin K epoxide reductase (VKOR). For most indications, warfarin is dosed to achieve an international normalized ratio (INR) of 2.0 to 3.0. Key2 When the INR drops below 2.0, patients are considered to be subtherapeutic and at a higher risk for thrombotic complications; Bleeding events while on warfarin are common, with an annual bleeding event rate between 1.7% and 3.4% in the United States.6 Hemorrhagic complications are responsible for more than 60,000 annual emergency department visits in VKA-treated patients.7 Of all VKA-treated patients, between 3% and 7% will require rapid reversal for either VKAassociated major bleed or for an emergent surgical procedure. 8 The administration of vitamin K (phytonadione) has the ability to overcome the inhibition of VKOR and reverse anticoagulation. Although there are other therapies to correct excessive anticoagulation such as fresh frozen plasm...

Effect of vitamin K administration on rate of warfarin reversal

“…The route and baseline INR relationships have been previously reported in the literature; however, analyses of vitamin K dose have been contradictory . Variability in clinical practice and these results may be related to inconsistent or incomplete guideline recommendations …”

“…Guidelines fail to fully address INR reversal in the setting of an upcoming surgical procedure or other non–life‐threatening bleeding indications . Using blood products or procoagulants for these indications, despite cost and risk, is common.…”

“…2,3,5,6 Variability in clinical practice and these results may be related to inconsistent or incomplete guideline recommendations. [8][9][10] Guidelines fail to fully address INR reversal in the setting of an upcoming surgical procedure or other non-lifethreatening bleeding indications. [8][9][10] Using blood products or procoagulants for these indications, despite cost and risk, is common.…”

“…[8][9][10] Guidelines fail to fully address INR reversal in the setting of an upcoming surgical procedure or other non-lifethreatening bleeding indications. [8][9][10] Using blood products or procoagulants for these indications, despite cost and risk, is common. These reversal interventions may be unnecessary, as our results support that vitamin K monotherapy begins to reverse INR immediately after administration.…”

Reversal of anticoagulation with four-factor prothrombin complex concentrate without concurrent vitamin K (phytonadione) for urgent surgery in a patient at moderate-to-high risk for thromboembolism

“…4F-PCC is recommended in preference to fresh-frozen plasma (FFP) for major bleeding and urgent reversal for life-saving surgery due to its faster onset of action and easier dose delivery. When 4F-PCC is given, simultaneous administration of intravenous vitamin K (phytonadione) is recommended 2 3. 4F-PCC has primarily been evaluated in clinical trials in comparison with FFP, with both arms receiving vitamin K 4 5.…”