How to manage a patient with a subtherapeutic International Normalized Ratio (INR)?

Management of Subtherapeutic INR

For patients with subtherapeutic INR on warfarin, increase the total weekly warfarin dose by 5-20% and recheck INR in 1-2 weeks for those at low thrombotic risk; for high-risk patients (mechanical heart valves, recent thromboembolism, atrial fibrillation with other risk factors), initiate bridging anticoagulation with therapeutic-dose LMWH or unfractionated heparin until INR returns to therapeutic range. 1

Risk Stratification

High-risk patients requiring bridging therapy include: 2, 1

• All patients with mechanical mitral or tricuspid valve replacements
• Patients with mechanical aortic valve replacements PLUS any of: atrial fibrillation, previous thromboembolism, LV ejection fraction <30%, hypercoagulable condition, older-generation mechanical valves, or multiple mechanical valves
• Recent venous thromboembolism (within 3 months)

Low-risk patients include those with atrial fibrillation without mechanical valves, remote history of VTE (>3 months), or newer-generation bileaflet mechanical aortic valves without additional risk factors. 1

Dose Adjustment Strategy

For a single slightly subtherapeutic INR in previously stable patients: 2, 1

• If INR is only 0.2-0.3 units below target range, consider continuing current dose with repeat INR in 1 week rather than adjusting
• This approach is supported by research showing that patients with stable anticoagulation who experience isolated subtherapeutic INR have only 0.4% risk of thromboembolism in 90 days 3

For persistently subtherapeutic INR or INR >0.5 units below target: 1, 4

• Increase total weekly warfarin dose by 5-20% (typically 10-15% for most patients)
• Recheck INR in 1-2 weeks after dose adjustment
• Avoid making dose changes for every minor INR fluctuation, as excessive dose adjustments worsen INR control 5

Bridging Anticoagulation Protocol

For high-risk patients, initiate bridging therapy immediately: 2, 1

• Low molecular weight heparin: 1 mg/kg (100 units/kg) subcutaneously every 12 hours
• Unfractionated heparin: 15,000 units subcutaneously every 12 hours (alternative option)
• Continue bridging until INR returns to therapeutic range for 2 consecutive measurements
• Do NOT use bridging for low-risk patients, as research demonstrates no benefit and potential harm 3

Monitoring Frequency

After dose adjustment: 6, 4

• Check INR 2-4 times per week initially after warfarin initiation or dose change
• Once stable in therapeutic range, gradually extend monitoring intervals
• Maximum interval of 4 weeks between INR checks for stable patients
• Return to more frequent monitoring (weekly) after any dose adjustment until stable again

Common Pitfalls to Avoid

Do NOT administer vitamin K for subtherapeutic INR: 2, 1

• Vitamin K is only indicated for supratherapeutic INR (>4-5) or bleeding
• Giving vitamin K when INR is low creates a hypercoagulable state and makes re-anticoagulation difficult
• This is particularly dangerous in patients with mechanical heart valves

Do NOT use loading doses to rapidly correct subtherapeutic INR: 6, 4

• Loading doses increase hemorrhagic complications without providing faster protection against thrombosis
• The anticoagulant effect of warfarin persists beyond 24 hours, so gradual dose increases are safer

Identify and address the underlying cause: 1, 7

• Medication non-adherence (most common cause)
• Drug interactions with enzyme inducers (rifampin, nafcillin, carbamazepine, phenytoin)
• Increased dietary vitamin K intake
• Malabsorption or diarrheal illness
• Address the root cause rather than simply increasing dose

Special Populations

Elderly or debilitated patients: 6, 4

• Use more conservative dose adjustments (5-10% of weekly dose rather than 15-20%)
• Consider lower target INR ranges when appropriate
• Monitor more frequently due to increased bleeding risk

Patients with mechanical heart valves: 2

• Target INR 2.5-3.5 for mitral position valves
• Target INR 2.0-3.0 for most bileaflet aortic valves
• Never allow prolonged periods of subtherapeutic anticoagulation without bridging therapy
• Even brief periods below therapeutic range significantly increase stroke risk

Optimal dose management strategy based on research: 5

• Only change warfarin dose when INR is ≤1.7 or ≥3.3 (for target range 2.0-3.0)
• This threshold-based approach achieves better time in therapeutic range (74%) compared to changing dose at every minor deviation (68%)
• Avoid reactive dose changes for INR values between 1.8-3.2 in stable patients