What is the protocol for using vitamin K (Vitamin K1, phytonadione) for warfarin reversal in patients with significant bleeding or elevated International Normalized Ratio (INR)?

From the Guidelines

For warfarin reversal in patients with significant bleeding or elevated INR, intravenous vitamin K1 (phytonadione) at a dose of 5-10 mg should be administered by slow IV infusion (over 20-30 minutes) along with prothrombin complex concentrate (PCC) or fresh frozen plasma, as recommended by the most recent guidelines 1. This approach is supported by the latest evidence, which emphasizes the importance of prompt and effective reversal of anticoagulation in patients with major bleeding or elevated INR. The use of vitamin K1 in conjunction with PCC is preferred over fresh frozen plasma due to its more rapid and complete factor replacement, as well as lower risk of thromboembolic complications 1. Key considerations in the management of warfarin reversal include:

• Monitoring INR frequently, typically at 6-12 hour intervals initially, with repeat dosing as needed
• Using the lowest effective dose of vitamin K1 to avoid warfarin resistance in subsequent days
• Administering vitamin K1 slowly to minimize the risk of anaphylactoid reactions
• Considering thromboprophylaxis as early as possible after bleeding has been controlled in patients who have received PCC. In patients with elevated INR (>9) without bleeding, a lower dose of 2.5-5 mg IV or oral vitamin K1 may be appropriate, while for moderately elevated INR (5-9) without bleeding, 1-2.5 mg oral vitamin K1 may be sufficient 1. It is essential to note that the management of warfarin reversal should be individualized based on the patient's specific clinical situation, including the severity of bleeding, INR level, and risk of thromboembolic events.

From the FDA Drug Label

OVERDOSAGE Signs and Symptoms Suspected or overt abnormal bleeding (e.g., appearance of blood in stools or urine, hematuria, excessive menstrual bleeding, melena, petechiae, excessive bruising or persistent oozing from superficial injuries) are early manifestations of anticoagulation beyond a safe and satisfactory level Treatment Excessive anticoagulation, with or without bleeding, may be controlled by discontinuing warfarin sodium tablets therapy and if necessary, by administration of oral or parenteral vitamin K1. If minor bleeding progresses to major bleeding, give 5 to 25 mg (rarely up to 50 mg) parenteral vitamin K1. The recommended dose to correct excessively prolonged prothrombin times caused by oral anticoagulant therapy is, 2. 5 mg to 10 mg or up to 25 mg initially. In some instances 50 mg may be required.

The protocol for using vitamin K (Vitamin K1, phytonadione) for warfarin reversal in patients with significant bleeding or elevated International Normalized Ratio (INR) involves:

• Discontinuing warfarin sodium tablets therapy
• Administering oral or parenteral vitamin K1, with doses ranging from 2.5 mg to 10 mg or up to 25 mg initially, and in some instances 50 mg may be required
• For minor bleeding that progresses to major bleeding, giving 5 to 25 mg (rarely up to 50 mg) parenteral vitamin K1 2
• Evaluating INR after 6 to 8 hours, and repeating the dose if INR remains prolonged 3

From the Research

Protocol for Vitamin K Administration

The protocol for using vitamin K (Vitamin K1, phytonadione) for warfarin reversal in patients with significant bleeding or elevated International Normalized Ratio (INR) involves administering vitamin K to begin reversing warfarin within 6 to 12 hours 4.

Key Considerations

• High vitamin K doses and intravenous route are associated with faster INR reversal 4.
• Baseline INR also influences the rate of correction and frequency of achieving complete reversal 4.
• Vitamin K alone may be sufficient in many cases of non-life-threatening bleeding, and prothrombin complex concentrate (PCC) administration can be avoided by better planning 5, 6.
• Intravenous vitamin K is more effective than oral vitamin K for urgent partial correction of warfarin 7.

Administration Guidelines

• The median dose of vitamin K used in studies ranged from 2.0 to 5.0 mg 4, 5, 7.
• The time to first INR follow-up after vitamin K administration averaged 10.5 hours 4.
• Repeat testing of the INR within 5 hours is recommended to assess the effectiveness of vitamin K alone 5.

Comparison with Other Reversal Agents

• Low-dose recombinant Factor VIIa (rFVIIa) was more likely than 3-factor prothrombin complex concentrate (PCC3) to reverse warfarin anticoagulation, with a lower follow-up INR and larger percent change in INR 8.
• However, thromboembolic events were equivalent in patients receiving PCC3 and LDrFVIIa 8.

Clinical Implications

• Delays in administration of PCC and vitamin K should be avoided, especially in cases of intracranial hemorrhage, where mortality is high 6.
• Simple dosing structures and availability of PCC stocks within emergency departments can help reduce treatment delays 6.