How soon after administering Vitamin K (Vit K) can the International Normalized Ratio (INR) be repeated?

From the Guidelines

After administering Vitamin K to reverse warfarin anticoagulation, INR should be rechecked within 24 hours, as oral vitamin K1, 1 to 2.5 mg, more rapidly lowers the INR to 5 within 24 hours than simply withholding warfarin 1.

Key Considerations

• The timing of INR recheck depends on the clinical urgency and the route of administration, with intravenous Vitamin K administration showing effects within 1-2 hours and reaching maximum effect at 6-8 hours, while oral Vitamin K typically takes 24-48 hours for full effect.
• For patients with serious bleeding or requiring urgent procedures, INR should be checked at 6-8 hours after intravenous Vitamin K administration.
• For less urgent situations with oral Vitamin K, checking INR at 24 hours is appropriate, as seen in a prospective study of 62 warfarin-treated patients with INR values between 4 and 10, where warfarin was omitted, and vitamin K1, 1 mg, was administered orally, resulting in a lower INR in 95% of patients after 24 hours 1.
• The minimum effective dose of Vitamin K should be used when temporary reversal is intended, as its effect can last several days, potentially making the patient resistant to warfarin when anticoagulation is restarted.

Clinical Implications

• The American College of Chest Physicians published recommendations for managing patients on coumarin anticoagulants who need their INRs lowered, which include omitting the next dose of warfarin and administering vitamin K1 (1 to 2.5 mg) orally if the patient is at increased risk of bleeding 1.
• In cases of life-threatening bleeding or serious warfarin overdose, prothrombin complex concentrate replacement therapy is indicated, supplemented with 10 mg of vitamin K1 by slow intravenous infusion; this can be repeated, according to the INR 1.

From the Research

Timing of INR Repeat after Vitamin K Administration

• The timing of INR repeat after vitamin K administration can vary depending on several factors, including the dose and route of vitamin K administration, as well as the patient's baseline INR 2, 3.
• Studies have shown that vitamin K can start to reverse warfarin's effects within 6 to 12 hours, but this may occur sooner 2.
• One study found that the time to first INR follow-up after vitamin K administration averaged 10.5 ± 4.2 hours, with a significant decrease in INR values detected in comparison to the baseline INR 2.
• Another study found that intravenous vitamin K reduced INR more rapidly than oral vitamin K, with INR values decreasing significantly within 12 hours of administration 3.

Factors Influencing INR Reversal

• The dose and route of vitamin K administration can influence the rate of INR reversal, with higher doses and intravenous administration associated with faster INR reversal 2, 3.
• The patient's baseline INR can also influence the rate of INR reversal, with higher baseline INR values associated with rapid INR change and lower baseline INR values associated with complete reversal 2.
• Other factors, such as the patient's age, medical history, and concomitant medications, can also affect the risk of bleeding and the need for INR reversal 4.

Comparison of Reversal Strategies

• Studies have compared the effectiveness of different reversal strategies, including vitamin K, fresh frozen plasma (FFP), and prothrombin complex concentrate (PCC) 5, 6.
• One study found that PCC was more effective than FFP in reversing warfarin's effects, with a higher proportion of patients achieving normal INR values and a shorter time to INR correction 6.
• Another study found that fixed, low-dose activated PCC was safe and effective in reversing warfarin's effects in patients with traumatic intracranial hemorrhage 5.