How to manage a patient with a subtherapeutic International Normalized Ratio (INR) on warfarin (coumarin) therapy?

Management of Subtherapeutic INR on Warfarin

For patients with a single subtherapeutic INR value who previously had stable therapeutic INRs, continue the current warfarin dose without adjustment and retest the INR within 1-2 weeks without administering bridging therapy with heparin. 1

Assessment Approach

• First determine if the subtherapeutic INR is an isolated event or part of a persistent pattern, considering the patient's indication for anticoagulation and their risk for thromboembolism 1
• Evaluate potential causes of the subtherapeutic INR, including:
  • Medication non-adherence
  • Drug interactions (many medications can decrease warfarin's effect)
  • Dietary changes (increased vitamin K intake)
  • Use of tobacco products (smokeless tobacco can significantly reduce INR) 2
  • Changes in alcohol consumption 3

Management Algorithm

For Single Subtherapeutic INR with Previously Stable Therapeutic INRs:

• Continue the current warfarin dose without adjustment 1
• Schedule follow-up INR testing within 1-2 weeks 1
• Do not administer bridging therapy with heparin, as evidence shows no significant difference in thromboembolic events between patients with a single low INR and those with therapeutic INRs 1, 4

For Persistent Subtherapeutic INRs:

• For patients requiring dosage adjustments, modify the total weekly dose by 5-20% based on the measured INR values and clinical factors 5
• Monitor INR more frequently (2-4 times per week) until stable therapeutic values are achieved 5
• Consider factors that may contribute to persistent subtherapeutic INRs:
  • Low daily warfarin dose (≤6 mg/day), especially in patients on high-intensity regimens (INR 2.5-3.5) 6
  • Drug interactions affecting warfarin metabolism 3

Special Considerations

• For patients with mechanical heart valves, a higher risk of thromboembolism exists with subtherapeutic INRs, but bridging is still not routinely recommended for a single subtherapeutic value 1
• For patients with recent thromboembolism or very high-risk conditions, individual risk assessment may warrant more aggressive management 1
• Patients receiving low-dose warfarin (≤6 mg/day) on high-intensity regimens (target INR 2.5-3.5) have >50% risk of subtherapeutic INRs and may require more careful monitoring 6

Follow-up Recommendations

• Once the patient returns to therapeutic range, resume regular monitoring schedule 1
• For patients with consistently stable INRs, INR testing frequency can be extended up to 4-6 weeks 1, 5
• Consider implementing a more systematic approach to oral anticoagulation management, including patient education about factors that can affect INR 1

Common Pitfalls to Avoid

• Unnecessarily administering bridging therapy for a single subtherapeutic INR, which increases bleeding risk without clear benefit 1, 4
• Making large dose adjustments based on a single subtherapeutic INR reading, which can lead to INR instability 1, 5
• Failing to identify and address modifiable factors contributing to subtherapeutic INRs, such as medication interactions or dietary changes 3
• Overlooking the use of smokeless tobacco, which can significantly reduce INR due to high vitamin K content 2