When should vitamin K1 (phytonadione) be administered to an adult patient with warfarin overdose and elevated International Normalized Ratio (INR)?

Vitamin K Administration for Warfarin Overdose

Algorithm Based on INR Level and Bleeding Status

For warfarin overdose, vitamin K administration depends critically on the INR level and presence of bleeding: give no vitamin K for INR <5.0 without bleeding, oral vitamin K 1-2.5 mg for INR 5.0-9.0 with bleeding risk factors, oral vitamin K 2.5-5 mg for INR >10 without bleeding, and IV vitamin K 5-10 mg plus 4-factor PCC for any active bleeding. 1

INR 4.5-5.0 Without Bleeding

• Withhold warfarin for 1-2 doses and monitor serial INR determinations without administering vitamin K 2
• 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, alcohol use) 2
• Resume warfarin at 10-15% lower weekly dose once INR returns to therapeutic range 2

INR 5.0-9.0 Without Bleeding

• Withhold warfarin and monitor serial INR determinations as the primary intervention 1, 2
• Add oral vitamin K 1-2.5 mg only if the patient has increased bleeding risk factors (advanced age, history of bleeding, concomitant antiplatelet drugs, renal failure, alcohol use) 1, 2
• The American College of Cardiology specifically recommends against routine vitamin K use in this range, as randomized trials show no reduction in major bleeding despite faster INR normalization 1
• Oral vitamin K achieves INR <4.0 within 24 hours in 85% of patients when used 1, 3

INR >10 Without Bleeding

• Immediately withhold warfarin and administer oral vitamin K 2.5-5 mg 1, 2
• Recheck INR within 24 hours to confirm appropriate reduction 1, 2
• The bleeding risk becomes clinically significant at INR >10, with one prospective series showing 3.9% major bleeding rate at 90 days even without initial bleeding 1

Active Bleeding (Any INR Level)

For major bleeding:

• Administer 5-10 mg IV vitamin K by slow infusion over 30 minutes 1, 3
• Consider adding 4-factor PCC 25-50 U/kg IV if bleeding is life-threatening, at critical sites (intracranial, intraspinal, intraocular, pericardial, retroperitoneal), or causing hemodynamic instability 1

For life-threatening bleeding:

• Immediately administer 4-factor PCC plus 10 mg IV vitamin K, targeting INR <1.5 1, 3
• PCC dosing algorithm based on INR: 25 U/kg if INR 2-4,35 U/kg if INR 4-6,50 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, 3

Route of Administration Considerations

Oral route is preferred for all non-emergency situations due to predictable effectiveness (95% of patients show INR reduction within 24 hours), convenience, and safety 1, 2

IV route advantages:

• Achieves faster partial correction: 44% of IV patients reach INR ≤2 within 12 hours versus only 14% with oral administration 1, 4
• However, IV administration carries risk of anaphylactoid reactions (3 per 100,000 doses) that can result in cardiac arrest, severe hypotension, and bronchospasm 1, 3
• Must be given by slow infusion over 30 minutes to minimize anaphylaxis risk 1, 3

Subcutaneous route is not recommended as it does not correct INR as rapidly or effectively as IV administration 5

Critical Dosing Caveats

Never exceed 10 mg vitamin K, as higher doses create a prothrombotic state and prevent re-warfarinization for days 1, 3

Avoid high-dose vitamin K (≥10 mg) in non-bleeding situations, as this creates warfarin resistance for up to one week and makes re-anticoagulation difficult 1, 2, 3

For patients requiring ongoing anticoagulation (mechanical heart valves), use low-dose vitamin K (1-2 mg) to avoid difficulty achieving therapeutic INR post-procedure 1

Monitoring Requirements

• Recheck INR within 24-48 hours after any vitamin K administration to confirm appropriate reduction 1, 2
• For PCC administration, recheck INR 15-60 minutes after administration to assess degree of correction 1
• Continue monitoring INR every 6-8 hours for the next 24-48 hours, as some patients require over a week to clear warfarin 1
• Monitor regularly over the next week, as a minority of patients may need additional vitamin K 1

Special Populations and Pitfalls

Patients with history of anaphylaxis:

• IV vitamin K is absolutely contraindicated regardless of INR level or bleeding status 1
• Oral administration is the only safe route even in urgent situations 1
• For major bleeding, use 4-factor PCC 25-50 U/kg IV plus oral vitamin K 5-10 mg simultaneously 1

Elderly patients (>65 years):

• Have higher bleeding risk at any given INR level 1, 2
• Require more cautious management and lower threshold for vitamin K administration 1, 2

Mechanical heart valve patients:

• Weigh thromboembolism risk carefully against bleeding risk 2
• Use minimal vitamin K doses necessary to avoid prolonged warfarin resistance 1

Common Pitfalls to Avoid

• Do not give vitamin K routinely for INR 4.5-10 without bleeding, as this provides no reduction in major bleeding and may complicate re-anticoagulation 1
• Do not use fresh frozen plasma (FFP) if PCC is available, as PCC achieves INR correction within 5-15 minutes versus hours with FFP 1, 3
• Do not forget to investigate and address the cause of INR elevation (drug interactions, dietary changes, intercurrent illness, medication non-adherence) before resuming therapy 2
• Do not restart warfarin until bleeding is completely controlled and the source is identified and treated 1

Thromboprophylaxis After PCC

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, particularly in trauma patients 1, 3