Management of Elevated INR
For elevated INR without bleeding, management is stratified by INR level: hold warfarin and monitor for INR 4.0-5.0; hold 1-2 doses with optional oral vitamin K (1.0-2.5 mg) for INR 5.0-9.0 in high-risk patients; and suspend warfarin completely with oral vitamin K (2.5-5 mg) for INR >9.0. 1
Management Algorithm Based on INR Level (No Bleeding)
INR 4.0-5.0
- Hold the next warfarin dose and recheck INR in 24-48 hours 1
- Resume warfarin at a reduced dose once INR approaches therapeutic range 2
- No vitamin K is typically needed at this level 1
INR 5.0-9.0
- Suspend warfarin for 1-2 doses 1
- Administer oral vitamin K₁ (1.0-2.5 mg) if the patient has high bleeding risk 1
- High bleeding risk factors include: age >65 years, history of stroke or GI bleeding, renal insufficiency, anemia, concomitant antiplatelet agents or NSAIDs, and hypertension 3, 4
- The INR should decrease within 24-48 hours after vitamin K administration 1, 5
- Recheck INR within 24-48 hours 1
INR >9.0
- Completely suspend warfarin 1
- Administer oral vitamin K₁ (2.5-5 mg) 1, 2
- For INR >10.0, consider fresh frozen plasma in addition to vitamin K 1
- Monitor INR within the first 24 hours 1
- Note that hospitalized patients with INR >9 may not respond quickly to warfarin withdrawal or vitamin K alone, and plasma infusion may be needed to reduce INR within 24 hours 4
Management of Elevated INR With Bleeding
Minor Bleeding
- Suspend warfarin immediately 1
- Administer oral vitamin K₁ (2.0-4.0 mg) 1
- Give additional vitamin K₁ (1.0-2.0 mg) if INR remains elevated after 24 hours 1
- Monitor INR closely until stable 1
Major or Life-Threatening Bleeding
- Hospitalize the patient immediately 1, 6
- Administer vitamin K₁ (5-10 mg) by slow intravenous infusion 1, 6
- Administer prothrombin complex concentrate or fresh frozen plasma 1, 6
- Plasma infusion immediately drops INR to approximately 2.4 4
- Frequent INR monitoring is essential 6
Special Populations and Considerations
Patients With Mechanical Heart Valves
- Do not use intravenous vitamin K in patients with prosthetic heart valves and elevated INR without bleeding due to risk of valvular thrombosis 1
- Hospitalization is recommended to allow INR to decrease gradually 1
- The target INR for mechanical valves ranges from 2.0-3.0 (aortic St. Jude) to 2.5-3.5 (mitral position or tilting disk valves) 3
Intracranial Hemorrhage
- Always reverse anticoagulation immediately 1
- Anticoagulation can be resumed after 1 week if clinically appropriate 1
Investigation of Underlying Causes
Always investigate why the INR became elevated to prevent recurrence 1:
- Review all medications for drug interactions (antibiotics, NSAIDs, amiodarone, azole antifungals) 3
- Assess dietary changes affecting vitamin K intake 2
- Evaluate for acute illness, liver disease, or heart failure 3
- Check for medication non-adherence or accidental overdose 2
- Consider alcohol use, which is associated with increased bleeding risk 4
Monitoring and Follow-Up
- Increase INR monitoring frequency until stability is achieved 1
- After warfarin interruption without vitamin K, INR returns to normal in 4-5 days 7, 1
- With vitamin K administration, INR declines substantially within 24 hours 7
- Once stable, gradually extend monitoring intervals up to maximum of 4-6 weeks 2
Critical Pitfalls to Avoid
Excessive Vitamin K Dosing
- Avoid high doses of vitamin K₁ (e.g., 10 mg) unless there is major bleeding, as this can cause warfarin resistance for up to a week 7, 1
- High doses may lower INR more than necessary and create difficulty re-establishing therapeutic anticoagulation 7
Route of Administration Errors
- Avoid intravenous vitamin K when not necessary due to risk of anaphylactic reactions 7, 1
- Oral administration is preferred for non-emergent situations 5
- Subcutaneous administration may cause cutaneous reactions 5
Failure to Investigate Root Cause
- Not investigating the underlying cause of elevated INR leads to recurrences 1
- Drug interactions are a common and preventable cause 3