From the Guidelines
For very high INR values, 10 mg of intravenous vitamin K is recommended in cases of serious bleeding or INR values above 20, while 2.5-5 mg of oral vitamin K is often recommended for INR values greater than 9 without bleeding. The dose of vitamin K for very high INR values depends on the severity and urgency of the situation.
- For INR values greater than 9 without bleeding, 2.5-5 mg of oral vitamin K is often recommended 1.
- For INR values above 20 or in cases with serious bleeding, 10 mg of intravenous vitamin K may be necessary 1. The intravenous route provides faster reversal but carries a small risk of anaphylactoid reactions.
- Oral vitamin K typically takes 24-48 hours for full effect 1. In addition to vitamin K, patients with very high INR may require fresh frozen plasma, prothrombin complex concentrate, or recombinant factor VIIa for immediate reversal in emergency situations.
- After administering vitamin K, INR should be rechecked within 12-24 hours to assess response 1. The underlying cause of the elevated INR should also be addressed, which may include adjusting the warfarin dose or addressing drug interactions, dietary changes, or illness that may have contributed to the high INR 1.
From the FDA Drug Label
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. Evaluate INR after 6 to 8 hours, and repeat dose if INR remains prolonged. Modify subsequent dosage (amount and frequency) based upon the INR or clinical condition.
The dose of vitamin K for very high INR is 2.5 mg to 10 mg or up to 25 mg initially, and in some instances up to 50 mg may be required. The dose should be adjusted based on the INR response, with evaluation after 6 to 8 hours and repeat dose if INR remains prolonged 2.
From the Research
Vitamin K Dosing for High INR
- The dose of vitamin K for very high INR is not explicitly stated in the provided studies, but it is mentioned that a nonbleeding patient with an INR of 9 can be given low-dose vitamin K1 (eg, 2.5 mg phytonadione, by mouth) 3.
- The use of prothrombin complex concentrates (PCC) is also recommended for urgent reversal of warfarin, especially in patients with life-threatening bleeding or requiring urgent surgery 4, 5, 6, 7.
- PCC has been shown to be superior to fresh frozen plasma (FFP) for emergency reversal of vitamin K antagonists, with better reversal of INR, lower risk of treatment-related adverse events, and reduced 90-day all-cause mortality 4, 6.
- The dose of PCC used in these studies varied, with some using a fixed dose of 25-50 U/kg 5 and others using a fixed dose of 1000 units regardless of weight or presenting INR 7.
Reversal of Warfarin Anticoagulation
- The goal of warfarin reversal is to rapidly correct the INR and prevent further bleeding or complications.
- The use of vitamin K1 and PCC has been shown to be effective in reversing warfarin anticoagulation, with PCC being more rapid and effective in correcting INR 4, 5, 6, 7.
- The choice of reversal agent and dose should be individualized based on the patient's specific situation and clinical factors, such as the severity of bleeding and the presence of other medical conditions.