What dose of vitamin K (Vit K) can be given to a patient for reversal of warfarin-induced anticoagulation?

Vitamin K Dosing for Warfarin Reversal

The dose of vitamin K depends entirely on the clinical scenario: for INR 4.5-10 without bleeding, use 1-2.5 mg oral vitamin K (or withhold warfarin alone); for INR >10 without bleeding, use 3-5 mg oral vitamin K; for serious bleeding, use 5-10 mg IV vitamin K by slow infusion; and for life-threatening bleeding, use 10 mg IV vitamin K plus 4-factor prothrombin complex concentrate (PCC). 1, 2, 3

Clinical Algorithm Based on INR and Bleeding Status

INR 4.5-10 Without Bleeding

• Routine vitamin K is NOT recommended for most patients in this range—simply withholding warfarin is sufficient 4, 2
• The American College of Chest Physicians explicitly recommends against routine vitamin K use (Grade 2B recommendation), as randomized trials show no reduction in major bleeding despite faster INR normalization 4
• Consider adding 1-2.5 mg oral vitamin K only if the patient has high bleeding risk factors: age >65 years, history of stroke or GI bleeding, renal insufficiency, anemia, or concomitant antiplatelet drugs 1, 2
• This low dose achieves INR <4.0 within 24 hours in 85% of patients without causing warfarin resistance 3

INR >10 Without Bleeding

• Administer 3-5 mg oral vitamin K in addition to holding warfarin 1, 2, 3
• This dose typically lowers INR within 24-48 hours 2
• The bleeding risk becomes clinically significant at this level, with one prospective series showing 3.9% major bleeding rate at 90 days even without initial bleeding 4

Serious/Major Bleeding (Non-Life-Threatening)

• Give 5-10 mg IV vitamin K by slow infusion over 30 minutes 1, 3, 5
• Major bleeding is defined as clinically overt bleeding with hemoglobin decrease ≥2 g/dL 1
• IV administration begins reversing warfarin immediately (within 0-4 hours), though complete reversal takes longer 6
• Critical safety point: IV vitamin K must be infused slowly (not exceeding 1 mg per minute) due to anaphylactoid reaction risk of 3 per 100,000 doses, which can cause cardiac arrest 1, 3, 5

Life-Threatening Bleeding or Emergency Surgery

• Administer 10 mg IV vitamin K plus 4-factor PCC (25-50 U/kg based on INR level) 1, 3
• PCC dosing algorithm: 25 U/kg for INR 2-4,35 U/kg for INR 4-6, and 50 U/kg for INR >6 1
• Target INR <1.5 for hemostasis 1
• Vitamin K must be co-administered with PCC because factor VII in PCC has only a 6-hour half-life, requiring vitamin K to stimulate endogenous production of clotting factors 1, 3
• PCC achieves INR correction within 5-15 minutes versus hours with vitamin K alone 3

Route of Administration Considerations

Oral vs. IV Vitamin K

• Oral route is preferred for non-bleeding scenarios due to lower risk of anaphylactoid reactions 7
• IV route achieves faster partial correction: 44% of IV patients reach INR ≤2 within 12 hours versus only 14% with oral administration 8
• Subcutaneous route should be avoided due to unpredictable absorption and cutaneous reactions 7

Dose-Response Relationships

• Higher doses (10 mg) and IV route are associated with faster INR reversal 6, 8
• However, the preadministration INR and time after administration are more important determinants of post-administration INR than the actual dose given (in the 1-10 mg range) 8
• Research shows vitamin K begins reversing warfarin immediately after administration, with significant INR decrease detectable within 0-4 hours 6

Critical Pitfalls and Caveats

Warfarin Resistance from Excessive Vitamin K

• Do not exceed 10 mg vitamin K, as higher doses create a prothrombotic state and prevent re-warfarinization for up to one week 1, 3
• High-dose vitamin K (≥10 mg) may require heparin bridging when warfarin needs to be resumed 2, 3
• For mechanical valve patients requiring urgent surgery, use lower doses (1-2 mg oral vitamin K) to avoid difficulty achieving therapeutic INR post-procedure 1

Monitoring Requirements

• Recheck INR 15-60 minutes after PCC administration to assess degree of correction 1
• Monitor INR serially every 6-8 hours for the first 24-48 hours, then regularly over the next week, as some patients require >1 week to clear warfarin 1
• If INR remains ≥1.4 within 24-48 hours after initial PCC, consider fresh frozen plasma 1

Thrombotic Risk

• PCC use increases risk of venous and arterial thrombosis during the recovery period 1, 3
• Thromboprophylaxis must be considered as early as possible after bleeding control is achieved 1
• The absolute risk of thromboembolism from overcorrection appears similar to the bleeding risk from over-anticoagulation 7

Special Populations

• Advanced age (>65-75 years) critically amplifies bleeding risk at any given INR level 1
• Vitamin K is less effective for over-anticoagulation with acenocoumarol or phenprocoumon compared to warfarin 7