When should vitamin K (phytonadione) be administered to a patient on warfarin therapy with an elevated International Normalized Ratio (INR)?

When to Administer Vitamin K for Elevated INR

For patients on warfarin with elevated INR, vitamin K administration depends on the INR level and bleeding status: withhold warfarin alone for INR 4.5-9.0 without bleeding in low-risk patients; add oral vitamin K 1-2.5 mg for INR 5.0-9.0 with bleeding risk factors; give oral vitamin K 2.5-5 mg for INR >10 without bleeding; and immediately administer IV vitamin K 5-10 mg plus 4-factor PCC for any major or life-threatening bleeding. 1, 2

INR 4.5-5.0 Without Bleeding

• Withhold warfarin for 1-2 doses and monitor serial INR determinations without vitamin K administration 1
• Restart warfarin at a reduced weekly dose of 10-15% less than the previous dose once INR returns to therapeutic range 1
• Vitamin K is not indicated at this level unless high bleeding risk factors are present (advanced age >65-75 years, history of bleeding, concomitant antiplatelet drugs, renal failure, or alcohol use) 1

INR 5.0-9.0 Without Bleeding

• Withhold warfarin and monitor serial INR determinations for most patients without additional bleeding risk factors 1, 3
• Add oral vitamin K 1.0-2.5 mg only if the patient has increased bleeding risk factors such as advanced age, history of bleeding, concomitant antiplatelet therapy, renal failure, or alcohol use 1, 3
• This approach is supported by randomized trials showing no reduction in major bleeding despite faster INR normalization with routine vitamin K use 1
• Oral vitamin K at this dose achieves INR <4.0 within 24 hours in 85% of patients 1

INR >10 Without Bleeding

• Immediately withhold warfarin and administer oral vitamin K 2.5-5 mg, with INR rechecked within 24 hours 1, 2
• The FDA-approved dosing range is 2.5-10 mg initially for anticoagulant-induced prothrombin deficiency 2
• A 2.5 mg oral dose is effective and safe, with major bleeding rates of only 3.7% in the first 90 days 4
• Oral vitamin K is preferred over IV or subcutaneous routes for non-bleeding situations due to predictable effectiveness (95% of patients show INR reduction within 24 hours), convenience, and lower risk of anaphylactoid reactions 1, 5
• The mean INR after 1 mg oral vitamin K drops from 5.79 to 2.86 within 16 hours 5

Major Bleeding (Any INR Level)

• Immediately administer IV vitamin K 5-10 mg by slow infusion over 30 minutes 1, 2
• Major bleeding is defined as clinically overt bleeding with hemoglobin decrease ≥2 g/dL 1
• Stop warfarin immediately and provide local therapy/manual compression if the bleeding source is accessible 1
• Monitor hemoglobin every 4-6 hours until stable and bleeding source is controlled 1

Life-Threatening Bleeding or Emergency Surgery

• Immediately administer 4-factor PCC 25-50 U/kg IV plus IV vitamin K 5-10 mg by slow infusion over 30 minutes, targeting INR <1.5 1
• Dosing algorithm for PCC based on INR: 25 U/kg if INR 2-4,35 U/kg if INR 4-6, and 50 U/kg if INR >6 1
• Always co-administer vitamin K with PCC because factor VII in PCC has only a 6-hour half-life, requiring vitamin K to stimulate endogenous production of vitamin K-dependent factors 1
• PCC achieves INR correction within 5-15 minutes versus hours with fresh frozen plasma 1
• Recheck INR 15-60 minutes after PCC administration to assess degree of correction 1

Route of Administration Considerations

• Oral route is preferred for all non-emergency situations due to predictable effectiveness, convenience, and safety 1, 3
• IV route is reserved only for major bleeding or life-threatening situations and must be given by slow infusion over 30 minutes due to risk of anaphylactoid reactions (3 per 100,000 doses) 6, 1
• IV vitamin K is absolutely contraindicated in patients with history of anaphylaxis; oral administration is the only safe route even in urgent situations 1
• IV route achieves faster partial correction: 44% of IV patients reach INR ≤2 within 12 hours versus only 14% with oral administration 1
• Subcutaneous route is not recommended as it is less effective than oral administration 3, 5

Critical Dosing Caveats

• Never exceed 10 mg vitamin K for non-bleeding situations, as higher doses create warfarin resistance for up to a week and make re-anticoagulation difficult 1
• The coagulant effects of oral vitamin K are not immediate; improvement of INR may take 1 to 8 hours 2
• If INR has not shortened satisfactorily within 12-48 hours after oral administration, repeat the dose 2
• Repeated large doses are not warranted in liver disease if the response to initial use is unsatisfactory, as failure to respond may indicate hepatic synthetic failure rather than vitamin K deficiency 6, 2

Post-Administration Monitoring

• Recheck INR within 24-48 hours after any vitamin K administration to confirm appropriate reduction 1
• Continue monitoring every 24-48 hours until INR stabilizes in therapeutic range 1
• Monitor INR regularly over the next week, as some patients require >1 week to clear warfarin and may need additional vitamin K 1
• Evaluate INR after 6-8 hours for hypoprothrombinemia due to other causes, and repeat dose if INR remains prolonged 2

Special Considerations for Mechanical Valve Patients

• In patients with mechanical valves requiring urgent surgery, use low-dose (1-2 mg) oral vitamin K to avoid difficulty achieving therapeutic INR post-procedure 1
• Higher doses are discouraged in this population to prevent prolonged warfarin resistance 1

Perioperative Management

• For patients with elevated INR (>1.5) 1-2 days before elective surgery/procedure, routine pre-operative vitamin K is not recommended 7
• Uncertainty about routine pre-operative vitamin K relates to the dose, limited availability of oral formulations, and potential for resistance to post-operative re-anticoagulation 7

Thromboprophylaxis After PCC Use

• PCC use increases risk of venous and arterial thrombosis during the recovery period 1
• Thromboprophylaxis must be considered as early as possible after bleeding control is achieved 1