Why does the international normalized ratio (INR) remain in the 2-3 range after vitamin K administration without restarting warfarin (coumarin)?

Understanding Persistent Therapeutic INR After Vitamin K Administration

Why the Route of Administration Matters

The persistence of INR in the 2-3 range several days after vitamin K administration without rewarfarinization strongly suggests oral rather than intravenous administration, because IV vitamin K produces more rapid and complete reversal while oral vitamin K has a slower, more gradual effect that can maintain therapeutic-range INRs for days. 1, 2

Pharmacokinetic Differences Between Routes

Intravenous Vitamin K Characteristics

• IV vitamin K begins reversing warfarin immediately (within 0-4 hours) and produces significantly faster INR reduction compared to oral administration 1
• At 12 hours post-administration, IV vitamin K reduces INR to approximately 1.91 versus 2.90 for oral vitamin K 2
• At 24 hours, IV achieves INR of approximately 1.54 versus 2.14 for oral 2
• IV route is associated with more complete reversal, with higher rates of achieving INR <1.5 (hazard ratio 1.8) 1

Oral Vitamin K Characteristics

• Oral vitamin K produces a more gradual, sustained effect that can keep INR in therapeutic range for 24-48 hours or longer 3, 4
• After oral administration of 1-2.5 mg, 95% of patients show INR reduction within 24 hours, with 85% achieving INR <4.0, but only 35% reaching INR ≤1.9 3
• The slower reversal pattern with oral vitamin K explains why INR would remain in the 2-3 range for several days 5

The Clinical Scenario Explained

Why INR 5.9 → 2.4 Suggests Oral Administration

• A reduction from 5.9 to 2.4 represents partial correction to therapeutic range, which is characteristic of oral vitamin K's gradual effect 3, 2
• If 5 mg was given IV, you would expect more complete reversal (INR closer to 1.5 or below) within 12-24 hours 1, 2
• The fact that INR remains stable in the 2-3 range days later without restarting warfarin is consistent with oral vitamin K's sustained but incomplete reversal 4, 5

Duration of Effect Without Warfarin

• When warfarin is simply stopped without vitamin K, INR falls from 2.0-3.0 to normal range over 4-5 days 3
• With oral vitamin K administration, the INR reduction is accelerated but not complete, maintaining therapeutic levels for 24-48 hours 3, 4
• The persistence of INR 2-3 several days later indicates ongoing vitamin K effect preventing complete normalization 4

Key Distinguishing Features

If IV Vitamin K Was Given (5 mg)

• Expect INR <2.0 within 12-24 hours 1, 2
• More likely to achieve complete reversal (INR <1.5) 1
• Rapid initial drop in first 4-12 hours 1, 6
• 44% achieve INR ≤2.0 within 12 hours with IV route 6

If Oral Vitamin K Was Given (5 mg)

• Expect INR reduction to 2-3 range within 24 hours 3, 4
• Sustained therapeutic INR for 24-48+ hours 3, 4
• Only 14% achieve INR ≤2.0 within 12 hours with oral route 6
• Gradual normalization over several days, which matches your clinical scenario 5

Clinical Implications

Why This Matters

• High-dose vitamin K (5-10 mg) can cause warfarin resistance for up to a week, regardless of route 3, 7
• If IV was given, the patient may be at increased thrombotic risk due to overcorrection 4
• If oral was given, the sustained therapeutic INR provides continued protection against thrombosis while minimizing bleeding risk 3

Common Pitfall

• Assuming all vitamin K acts the same regardless of route leads to inappropriate expectations for INR trajectory and timing of warfarin reinitiation 2, 6
• The dose of 5 mg is appropriate for INR >5.0, but route dramatically affects the reversal pattern 3, 8