Guidelines for the Administration of Vitamin K Drug Information Center

C-113 Chandler Medical Center, (859) 323-5320

Introduction In 2001, the American College of Chest Physicians (ACCP) Task Force on Antithrombotic Therapy published the proceedings of their Sixth Consensus Conference on antithrombotic therapy. These recommendations, published in CHEST, address the management of patients receiving oral anticoagulation therapy. Warfarin-associated coagulopathy, or excessive prolongation of the INR, places patients at an increased risk for severe bleeding complications. In addition, therapeutic INRs (usually values of 2-3) place patients at an increased risk for bleeding during invasive procedures. The CHEST Guidelines outline specific recommendations for the management of supratherapeutic INRs and for reversal of anticoagulation for invasive procedures. These recommendations are summarized in Table 1. WHAT’S THE PROBLEM? Complications associated with vitamin K1: • Subcutaneous: response to vitamin K1 may be unpredictable and delayed, allowing the patient to remain at an increased risk for bleeding. • High Doses: (via any route) can result in overcorrection of the INR with a subsequent increase in clotting risk, and warfarin resistance for up to a week. • Warfarin Resistance: can prolong hospital length of stay (if the patient is receiving a heparin drip) or increase the number of doses of low molecular weight heparin while waiting for a therapeutic INR on warfarin. • Intramuscular: never shown to be effective; associated with skin lesions and delayed cutaneous reactions (4 to 5 days after exposure). Intravenous: doses of 5-20mg can cause hypersensitivity reactions or anaphylaxis WHAT SHOULD WE DO? • When INR is <5, holding the warfarin dose is the safest option. • Oral vitamin K1 is the treatment of choice in many cases, especially when the patient is at increased risk for bleeding (history of bleeding or stroke, or serious comorbid conditions). • Because of the serious risk of anaphylaxis, the IV route should be reserved for patients who meet criteria indicated in CHEST Guidelines (see Table 1); it should be diluted (NSS or D5W) and administered at a maximum rate of 1mg/min. • Clinicians should become familiar with current recommendations for the administration of vitamin K1. Until larger, randomized trials are conducted, the current CHEST Guidelines are the most widely accepted recommendations available.

Table 1: Modified ACCP Consensus for Managing Patients with High INR Values*
INR Greater than therapeutic, but < 5 with no significant bleeding+ 5–9 (No significant bleeding+) 5–9 (Rapid reversal required for urgent surgery) >9 (No significant bleeding+) >20 OR significant bleeding+ Action / Recommendation Lower warfarin dose, OR omit a dose and resume therapy at a lower dose when the INR is within therapeutic range. Omit 1 or 2 doses (monitoring INR more frequently), and resume therapy at a lower dose when INR therapeutic, OR Omit a dose and administer vitamin K1 1.25 to 2.5 mg PO if patient at increased risk of bleeding. Administer vitamin K1 2.5 to 5 mg PO (INR to normalize in 24 hours); If INR still high, administer additional 1.25 to 2.5 mg vitamin K1 PO. Hold warfarin therapy AND administer vitamin K1 3.75 to 5 mg PO (monitor INR more frequently, and administer additional vitamin K1 in 24 to 48 hours if necessary); resume therapy at a lower dose when INR therapeutic. Hold warfarin therapy AND administer vitamin K1 10mg by slow IV infusion (1mg/min); may repeat every 12 hours if needed. (Supplement with fresh plasma, depending on urgency.)

* Doses have been rounded to comply with commercially available dosage forms. + Significant bleeding: Major (requiring treatment, medical evaluation, or at least 2 units of blood) or life-threatening (leading to cardiac arrest, surgical / angiographic intervention, or irreversible sequelae).

Table 2: Patients with Therapeutic INRs Requiring Reversal of Warfarin for Surgery
Recommendations Low risk* of thromboembolism (TE): Stop warfarin for 4 days prior to surgery, allow INR to return to nearnormal; post-op- administer prophylactic heparin doses (5000 Units SQ BID) briefly AND restart warfarin simultaneously. * Low risk: patients without TE for > 3months OR history of atrial fibrillation WITHOUT history of stroke. Intermediate risk of TE: Stop warfarin 4 days prior to surgery, start low-dose heparin (ex. heparin 5000 Units SQ BID)+ or prophylactic LMWH+ doses 2 days before surgery; post-op- continue heparin or LMWH prophylaxis PLUS simultaneous warfarin. High risk* of TE: Stop warfarin 4 days prior to surgery , start heparin+ or LMWH+ therapy at treatment doses (ex. heparin drip, target aPTT 1.5-2 x patient control) 2 days before surgery; post-op- continue heparin or LMWH treatment PLUS simultaneous warfarin until INR is therapeutic. * High risk: patients with < 3 month prior history of TE or mechanical mitral valve replacement. Patients with low risk of bleeding: Continue warfarin at lower doses (decrease dose 4-5 days before surgery) and operate at INR 1.3-1.5; post-op- initiate supplemental low-dose heparin, if needed, and restart previous warfarin dose. When holding warfarin for 4 days is not an option, patients with INR of >1.1 but <5 should receive vitamin K1 1.25 – 2.5mg PO.
Heparin infusion should be discontinued 5 hours prior to procedure; SQ heparin and LMWH should be discontinued 12-24 hours prior to procedure. TE=thromboembolism, LMWH=low molecular weight heparin
References: 1. Hirsh J, et al. Chest 2001;119: 8S-21S. 2. Ansell J, et al. Chest 2001;119: 22S-38S. 3. Taylor CT, et al. Pharmacotherapy 1999;19(12): 1415-25. 4. Shields R, et al. Mayo Clin Proc 2001;76: 260-266. 5. Wentzien TH, et al. Chest 1998;114(6): 1546-50.

Available dosage forms: • Phytonadione tablets: 5mg (can be cut to provide 1.25, 2.5, or 3.75 mg doses). • Phytonadione injection: aqueous 1mg/0.5mL or 10mg/mL ampules.

_________________________________________________________________________________________________________________ Approved by P&T Committee: 6/02 | Posted on: 3/04 | For Internal University of Kentucky Chandler Medical Center Use Only

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