When to correct a supratherapeutic International Normalized Ratio (INR)?

Management of Supratherapeutic INR

For patients with elevated INR without bleeding, management depends on the INR level: withhold warfarin for INR 3.0-5.0, withhold warfarin and consider oral vitamin K (1-2.5 mg) for INR 5.0-9.0 if bleeding risk factors are present, and give oral vitamin K (3-5 mg) for INR >9.0. 1

INR 3.0-5.0 Without Bleeding

• Withhold one dose of warfarin or reduce the dose, then resume at a lower dose when INR returns to therapeutic range 2
• No vitamin K administration is needed at this level 2
• Recheck INR within 24-48 hours to confirm appropriate reduction 1
• Evaluate for potential causes including drug interactions, dietary changes (particularly vitamin K intake), illness, or medication non-adherence 2, 1

INR 5.0-9.0 Without Bleeding

• Omit the next 1-2 doses of warfarin 1
• Administer oral vitamin K₁ (1-2.5 mg) if the patient has increased bleeding risk factors (elderly age >65 years, history of bleeding, concurrent antiplatelet therapy, recent surgery, uncontrolled hypertension) 1, 2
• The American College of Chest Physicians recommends withholding warfarin and observation as appropriate for INR 4.0-5.0 without bleeding 1
• After oral vitamin K₁ administration, INR typically decreases within 24 hours, with 95% of patients showing reduction and 85% achieving INR <4.0 1
• Recheck INR within 24-48 hours 1, 3
• Resume warfarin at a reduced dose (approximately 10-15% lower than previous weekly total) when INR approaches therapeutic range 1

INR >9.0 Without Bleeding

• Hold warfarin and administer oral vitamin K₁ (3-5 mg) 1
• Expect INR reduction within 24-48 hours 1
• The American Society of Hematology/International Society on Thrombosis and Haemostasis recommends that for pediatric patients, VKAs should be reversed with oral vitamin K for INR >10 2
• Recheck INR within 24 hours 1
• Resume warfarin at significantly reduced dose once INR is in therapeutic range 1

INR >10.0 Without Bleeding

• Administer oral vitamin K (vitamin K should be given for any INR >10) 2
• Hold warfarin until INR returns to therapeutic range 2
• Monitor INR closely with daily checks initially 2

Presence of Active Bleeding

Minor Bleeding with Elevated INR

• Hold warfarin 3
• Administer vitamin K₁ (5-10 mg) by slow intravenous infusion over 30 minutes 1
• Hospital admission for monitoring 3
• Frequent INR monitoring 3

Major or Life-Threatening Bleeding

• Immediate hospital admission 3
• Administer vitamin K₁ (10 mg) by slow IV infusion over 30 minutes 1
• Give prothrombin complex concentrate (PCC) or fresh frozen plasma 1, 3
• PCC is preferred over fresh frozen plasma due to faster onset of action (5-15 minutes vs. hours) 1
• Frequent INR monitoring 3

Important Considerations

Vitamin K Dosing Principles

• Avoid high-dose vitamin K (10 mg) for non-bleeding patients as it may cause warfarin resistance lasting up to one week 1, 4
• Low-dose oral vitamin K₁ (1-2.5 mg) is sufficient for INR 4-10 without bleeding 1
• Oral vitamin K is the treatment of choice for non-emergency INR reversal due to predictable effectiveness, convenience, and safety 1

Monitoring After Intervention

• INR should be rechecked within 24-48 hours after any intervention 1
• More frequent monitoring is required until INR stability is re-established 1
• When resuming warfarin, use approximately 10-15% lower weekly dose than before 1

Risk Factors Requiring More Aggressive Management

• Elderly patients (>65 years) have higher bleeding risk at any given INR level 1
• Patients with mechanical heart valves require careful balance between thromboembolism and bleeding risk 1
• Higher HAS-BLED scores and prolonged duration of warfarin therapy increase risk of supratherapeutic anticoagulation 5
• Concurrent antiplatelet therapy significantly increases bleeding risk 2

Common Pitfalls to Avoid

• Do not administer vitamin K unnecessarily for INR <5.0 without bleeding, as this can lead to warfarin resistance and difficulty re-establishing therapeutic anticoagulation 1
• Do not use high-dose vitamin K (10 mg) for asymptomatic patients with INR <9.0 1, 6
• Do not make dose adjustments for a single slightly out-of-range INR in otherwise stable patients 7
• The absolute daily risk of bleeding remains low even with INR 5-9 (0.96% 30-day major bleeding risk), but risk increases exponentially as INR rises above 5.0 6, 4
• Intervention with vitamin K among asymptomatic patients with INR <9 is not routine practice and should be reserved for those with bleeding risk factors 6

Special Populations

• For patients on therapeutic warfarin for other indications (e.g., mechanical valves, atrial fibrillation), do not initiate additional anticoagulant therapy until INR is <2.0 2
• In pregnant women, warfarin should be replaced with heparin during first trimester and last 6 weeks before delivery 2