When do we administer vitamin K (phylloquinone) to a patient on warfarin (coumarin) with an elevated international normalized ratio (INR)?

Vitamin K Administration in Warfarin Patients with Elevated INR

Clinical Decision Algorithm Based on INR Level and Bleeding Status

For patients on warfarin with elevated INR, vitamin K administration depends critically on three factors: the INR level, presence of active bleeding, and bleeding risk factors—with most non-bleeding situations managed by simply withholding warfarin rather than routinely giving vitamin K. 1

INR 4.5-10 Without Bleeding

• Withhold warfarin for 1-2 doses and monitor serial INR without giving vitamin K in most patients. 1, 2
• The American College of Chest Physicians explicitly recommends against routine vitamin K use in this range (Grade 2B), as randomized trials showed no reduction in major bleeding, thromboembolism, or mortality compared to simply withholding warfarin. 1
• Add oral vitamin K 1-2.5 mg only if high bleeding risk factors are present: advanced age (>65-75 years), history of bleeding, concomitant antiplatelet drugs, renal failure, or alcohol use. 2, 3
• This selective approach achieves INR <4.0 within 24 hours in 85% of patients who receive vitamin K. 4

INR >10 Without Bleeding

• Immediately withhold warfarin and administer oral vitamin K 5 mg (alternatively 2.5-5 mg range). 2, 3
• The bleeding risk becomes clinically significant at this level, with prospective data showing 3.9% major bleeding rate at 90 days even without initial bleeding. 1, 3
• Recheck INR within 24 hours after vitamin K administration to confirm appropriate reduction. 3
• A single 2.5 mg oral dose has been shown effective in prospective cohort studies of 107 patients with INR >10. 5

Major Bleeding (Any INR Level)

• Administer 5-10 mg IV vitamin K by slow infusion over 30 minutes plus 4-factor prothrombin complex concentrate (PCC) 25-50 U/kg IV. 2, 4
• The PCC dosing algorithm based on INR is: 25 U/kg if INR 2-4,35 U/kg if INR 4-6, and 50 U/kg if INR >6. 2, 4
• Always co-administer vitamin K with PCC because factor VII in PCC has only a 6-hour half-life—vitamin K is required to stimulate endogenous production of vitamin K-dependent factors and prevent "rebound" anticoagulation. 2, 4, 6
• PCC achieves INR correction within 5-15 minutes versus hours with fresh frozen plasma or vitamin K alone. 2, 4

Life-Threatening Bleeding

• Administer 10 mg IV vitamin K plus 4-factor PCC immediately, targeting INR <1.5. 2, 4
• Life-threatening sites include intracranial, intraspinal, intraocular, pericardial, retroperitoneal, intra-articular, or intramuscular with compartment syndrome. 2
• Recheck INR 30 minutes after PCC administration to assess degree of correction. 2

Route of Administration Considerations

• Oral vitamin K is preferred for all non-emergency situations due to predictable effectiveness (95% show INR reduction within 24 hours), convenience, and safety. 2
• IV vitamin K achieves faster partial correction (44% reach INR ≤2 within 12 hours vs 14% with oral), but carries risk of anaphylactoid reactions (3 per 100,000 doses). 2, 4
• IV vitamin K must be given by slow infusion over 30 minutes to minimize anaphylaxis risk, which can result in cardiac arrest, severe hypotension, and bronchospasm. 2, 4
• Subcutaneous vitamin K is not recommended as it is less effective than oral administration. 2

Critical Dosing Caveats and Pitfalls

• Never exceed 10 mg vitamin K, as higher doses create a prothrombotic state and cause warfarin resistance lasting up to one week, making re-anticoagulation extremely difficult. 2, 4
• High-dose vitamin K (≥10 mg) may require heparin bridging when warfarin needs to be resumed. 2, 4
• In patients with mechanical heart valves requiring urgent surgery, use lower doses (1-2 mg oral vitamin K) to avoid difficulty achieving therapeutic INR post-procedure. 2
• The preadministration INR and time after administration are more important determinants of post-administration INR than the actual vitamin K dose given (in the 1-10 mg range). 2

Post-Treatment Monitoring and Warfarin Resumption

• Recheck INR within 24-48 hours after any intervention to confirm appropriate reduction, and continue monitoring every 24-48 hours until INR stabilizes in therapeutic range. 2, 3
• When restarting warfarin, reduce the weekly total dose by 10-20% to prevent recurrent supratherapeutic INR. 2, 3
• Do not restart warfarin until bleeding is completely controlled, the source is identified and treated, and the patient is hemodynamically stable. 2
• Monitor INR regularly over the next week, as some patients require >1 week to clear warfarin and may need additional vitamin K. 2

Special Considerations

• PCC use increases thrombotic risk during the recovery period—thromboprophylaxis must be considered as early as possible after bleeding control is achieved. 2, 4
• In hospitalized patients with INR >9, withholding warfarin or vitamin K alone may be ineffective at reducing INR within 24 hours due to underlying disease and comorbidities, potentially requiring plasma infusion. 7
• For elective surgery with INR >1.5 measured 1-2 days preoperatively, routine pre-operative vitamin K is not recommended due to uncertainty about dosing and potential for resistance to post-operative re-anticoagulation. 1, 2