What is the expected decrease in International Normalized Ratio (INR) after administering 1 ampule (10 mg) of vitamin K intravenously to a patient with an elevated INR due to warfarin therapy?

Expected INR Reduction with 10 mg Intravenous Vitamin K

Administering 1 ampule (10 mg) of intravenous vitamin K will typically reduce the INR by approximately 3-4 points within 10-12 hours, though complete reversal to INR <1.5 occurs in only 14.5% of patients at 24 hours and 41.7% at 48 hours when vitamin K is used alone. 1

Mechanism and Timing of INR Reduction

• Vitamin K begins reversing warfarin immediately (within 0-4 hours), with rapid and steady INR change starting right after administration 1
• The traditional teaching that vitamin K takes 6-12 hours to work is outdated; INR reduction begins much sooner 1
• At 10-12 hours post-administration, the average INR decreases from baseline 4.7 ± 2.2 to 3.0 ± 1.9 1

Dose and Route Effects on INR Correction

• Intravenous vitamin K 10 mg is associated with faster INR reversal compared to lower doses (hazard ratio 2.4; 95% CI 1.4-4.2) 1
• IV route produces more rapid correction than oral administration, with INR values of 1.91 at 12 hours for IV versus 2.90 for oral 2
• INR reduction is similar for all IV vitamin K doses ≥2 mg, meaning doses above 2 mg don't necessarily produce proportionally greater reductions 2
• The baseline INR significantly influences the absolute magnitude of reduction—higher baseline INRs show more rapid absolute change 1, 2

Clinical Context for 10 mg IV Vitamin K

This dose is reserved for serious or life-threatening bleeding scenarios 3, 4:

• For serious bleeding: 5-10 mg IV vitamin K by slow infusion over 30 minutes 3, 4
• For life-threatening bleeding: 10 mg IV vitamin K plus prothrombin complex concentrate (PCC) 3, 4
• Vitamin K alone is insufficient for emergent reversal—PCC achieves INR <1.5 within 5-15 minutes, while vitamin K alone takes hours 4

Important Caveats and Pitfalls

• Always co-administer PCC with 10 mg vitamin K in life-threatening bleeding because factor VII in PCC has only a 6-hour half-life; vitamin K is needed to stimulate endogenous production of clotting factors 4
• Without vitamin K supplementation, INR may re-increase 12-24 hours after PCC administration, potentially causing clinical deterioration 5
• High-dose vitamin K (10 mg) creates warfarin resistance for up to one week, requiring heparin bridging if warfarin needs to be resumed 3, 6
• Anaphylactic reactions occur in 3 per 100,000 IV vitamin K doses; administer by slow infusion over 30 minutes 4
• Do not exceed 10 mg vitamin K, as higher doses create a prothrombotic state and prolong warfarin resistance 4

Practical Expectations by Clinical Scenario

For non-bleeding elevated INR (where 10 mg would be excessive):

• INR 5-9 without bleeding: Use 1-2.5 mg oral vitamin K, expecting 85% of patients to achieve INR <4.0 within 24 hours 7
• INR >10 without bleeding: Use 3-5 mg oral vitamin K, expecting INR reduction within 24-48 hours 3, 6

For serious bleeding with 10 mg IV vitamin K:

• Expect INR reduction to begin within 0-4 hours 1
• At 12 hours: Average INR reduction of approximately 2-3 points 1, 2
• At 24 hours: Only 14.5% achieve complete reversal (INR <1.5) with vitamin K alone 1
• This is why PCC is mandatory for life-threatening bleeding—vitamin K alone is too slow 4