What is the recommended intravenous (IV) dose of Vitamin K for reversing warfarin (Coumadin) anticoagulation effects?

Intravenous Vitamin K Dosing for Warfarin Reversal

For life-threatening bleeding or emergency surgery requiring warfarin reversal, administer 5-10 mg of vitamin K by slow intravenous infusion over 15-30 minutes, always in combination with 4-factor prothrombin complex concentrate (PCC), targeting an INR <1.5. 1, 2

Clinical Context and Dosing Algorithm

The IV vitamin K dose depends critically on the clinical scenario:

Life-Threatening Bleeding or Emergency Surgery

• Administer 10 mg IV vitamin K by slow infusion over 30 minutes PLUS 4-factor PCC immediately 1, 2
• This combination provides both immediate reversal (via PCC within 5-15 minutes) and sustained correction (via vitamin K stimulating endogenous factor production) 1, 2
• Target INR <1.5 for surgical procedures and emergency interventions 1, 2

Serious (Non-Life-Threatening) Bleeding

• Administer 5-10 mg IV vitamin K by slow infusion over 15-30 minutes 1, 3
• Consider adding PCC depending on bleeding severity and INR level 1
• The FDA label specifies doses of 2.5-10 mg initially, with rare instances requiring up to 25-50 mg 3

Anticoagulant-Associated Intracerebral Hemorrhage (ICH)

• Administer IV vitamin K immediately after PCC administration to prevent later INR increase and subsequent hematoma expansion 1
• The American Heart Association/American Stroke Association strongly recommends this combination for all VKA-associated ICH with INR ≥2.0 1

Critical Administration Details

Infusion Technique

• Always dilute in 25-50 mL normal saline and infuse over 15-30 minutes 1, 2
• Slow IV administration produces more predictable and rapid INR reduction (4-6 hours) compared to oral (18-24 hours) or subcutaneous (unpredictable) routes 1
• Modern IV vitamin K preparations have minimal anaphylactic risk (3 per 100,000 doses) when administered slowly 2

Why Vitamin K Must Accompany PCC

• Factor VII in PCC has a half-life of only 6 hours, requiring vitamin K to stimulate endogenous production of vitamin K-dependent factors for sustained reversal 2
• Without vitamin K co-administration, INR will re-elevate as PCC factors are metabolized 1, 2

Monitoring and Follow-Up

• Recheck INR 30 minutes after PCC administration to assess degree of correction 2
• If INR has not shortened satisfactorily within 6-8 hours after parenteral vitamin K, repeat the dose 3
• Monitor INR regularly over the next week, as some patients require additional vitamin K to clear warfarin completely 2

Important Caveats and Pitfalls

Dose Limitations

• Do not exceed 10 mg vitamin K in most situations, as higher doses create a prothrombotic state and prevent re-warfarinization for days 2
• The exception is rare cases where the FDA label permits up to 25-50 mg for severe anticoagulant-induced prothrombin deficiency 3

Thrombotic Risk

• PCC use increases thrombotic risk during recovery; consider thromboprophylaxis as early as possible after bleeding control 2
• 3-factor PCC carries higher thrombotic risk than 4-factor PCC 2

Warfarin Resistance

• High-dose vitamin K (≥10 mg) may cause warfarin resistance lasting up to one week 1, 4
• Resumption of warfarin after high-dose vitamin K may require heparin bridging until vitamin K effects reverse 2, 4

Fresh Frozen Plasma (FFP)

• Use FFP only if PCC is unavailable, as it requires hours for effect, needs ABO matching, and carries fluid overload risk 1, 2
• PCC contains 25 times the concentration of vitamin K-dependent factors compared to FFP 1

Onset of Action

• IV vitamin K begins reversing warfarin immediately (0-4 hours), with significant INR decrease detectable within the first 4 hours 5
• Research demonstrates rapid and steady INR change starts immediately after IV vitamin K administration, contrary to older teaching suggesting 6-12 hour delay 5
• Higher baseline INR and IV route are associated with faster INR reversal compared to oral administration 5, 6, 7