Guidelines for High INR and Vitamin K Administration
For patients with elevated INR due to warfarin therapy, the recommended approach is to hold warfarin, administer oral vitamin K at doses tailored to the INR level, and consider prothrombin complex concentrate (PCC) for severe elevations or active bleeding. 1
Management Based on INR Levels Without Bleeding
INR Above Therapeutic Range but <5
- Hold or reduce the next dose of warfarin
- Resume at a lower dose when INR approaches desired range
- No vitamin K administration necessary 2, 1
INR Between 5 and 9 Without Bleeding
- Omit next 1-2 doses of warfarin
- For patients at increased bleeding risk: Administer 1-2.5 mg oral vitamin K
- Resume warfarin at lower dose when INR falls into therapeutic range 2, 1
- Monitor INR within 24 hours after intervention 1
INR >9 Without Bleeding
- Hold warfarin
- Administer 3-5 mg oral vitamin K
- Monitor INR closely (every 6-12 hours until trending down) 1
- For INR >10: Oral vitamin K 2.5 mg is effective with low rates of major bleeding (3.7%) 3
Management of Elevated INR With Active Bleeding
Non-Major Bleeding
- Hold warfarin
- Apply direct pressure to wound for at least 15 minutes
- Consider 2-5 mg oral vitamin K if bleeding doesn't respond to local measures 1
Major Bleeding
- Hold warfarin
- Administer vitamin K 5-10 mg by slow IV infusion
- Consider prothrombin complex concentrate (PCC) or fresh frozen plasma
- PCC is preferred over fresh frozen plasma due to faster INR correction (within 15 minutes) 1, 4
Intracranial Hemorrhage
- Rapid reversal is essential
- Administer PCC and vitamin K immediately
- Target INR <1.4 within 1 hour of presentation 1
- Implementation of order sets and pharmacist verification significantly improves adherence to guideline-based management (76.5% vs 34.4%) 5
Route of Administration Considerations
Oral Vitamin K
- Predictably effective, convenient, and safe
- 1 mg oral vitamin K effectively lowers INR to <4 in 85% of patients within 24 hours 2
- Takes longer to work than IV administration (44% of IV group achieved INR ≤2 within 12 hours vs 14% for oral route) 6
Intravenous Vitamin K
- Produces rapid response but may be associated with anaphylactic reactions
- Should be administered by slow infusion (5-10 mg over 30 minutes)
- Preferred when rapid reversal is critical 2, 1
Subcutaneous Vitamin K
- Response is unpredictable and sometimes delayed
- Not recommended as first-line therapy 2
Monitoring After Intervention
- Recheck INR within 24 hours after any intervention
- Check INR daily until therapeutic range has been reached and sustained for 2 consecutive days
- Then check 2-3 times weekly for 1-2 weeks
- Adjust frequency based on stability 1
Important Caveats
- High doses of vitamin K (e.g., 10 mg) may lead to warfarin resistance for up to a week 2
- Resumption of warfarin after reversal requires careful dosage adjustment to avoid returning to a prethrombotic state 4
- For patients with intracranial hemorrhage, resuming warfarin after 7-10 days may be reasonable for high-risk patients (mechanical heart valves, atrial fibrillation with prior stroke) 1
- Computerized dosing algorithms have shown superior results compared to empirical dosing 2, 1
- The risk of thromboembolic events during warfarin cessation is approximately 2-5% within 30 days 1