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 near-
normal; 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: Available dosage forms:

1. Hirsh J, et al. Chest 2001;119: 8S-21S.
• Phytonadione tablets: 5mg (can be cut to provide
2. Ansell J, et al. Chest 2001;119: 22S-38S.
3. Taylor CT, et al. Pharmacotherapy 1999;19(12): 1.25, 2.5, or 3.75 mg doses).
1415-25. • Phytonadione injection: aqueous 1mg/0.5mL or
4. Shields R, et al. Mayo Clin Proc 2001;76: 260-266. 10mg/mL ampules.
5. Wentzien TH, et al. Chest 1998;114(6): 1546-50.

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