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

Management of Subtherapeutic INR in Patients on Warfarin Therapy

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

Assessment of Subtherapeutic INR

When faced with a subtherapeutic INR in a patient on warfarin therapy, the management approach should be guided by:

1. The degree of INR deviation from therapeutic range
2. The patient's clinical stability
3. The indication for anticoagulation
4. The presence of risk factors for thromboembolism

Initial Evaluation

• Determine if this is an isolated subtherapeutic INR or a pattern
• Assess for medication changes, dietary changes, or missed doses
• Evaluate for signs or symptoms of thromboembolism

Management Algorithm for Subtherapeutic INR

Single Subtherapeutic INR in Stable Patient

For patients with previously stable therapeutic INRs who present with a single subtherapeutic INR:

• Continue the current warfarin dose without adjustment 1
• Schedule INR retesting within 1-2 weeks 1
• Do not administer bridging therapy with heparin 1

This approach is supported by evidence showing that patients with stable INRs who experience a single subtherapeutic INR have a low risk of thromboembolism (0.4%) in the ensuing 90 days, similar to patients who maintain therapeutic anticoagulation (0.1%) 2.

Significantly Subtherapeutic INR or Multiple Low INRs

For patients with significantly subtherapeutic INR (>0.5 below target range) or multiple consecutive low INRs:

1. Increase the weekly warfarin dose by 5-20% 3
2. Monitor INR more frequently (e.g., twice weekly) until stable 3
3. Consider bridging therapy only for high-risk patients (mechanical heart valves, recent thrombosis, or known thrombophilia)

Dosing Adjustment Principles

• Avoid excessive dose changes for minor INR fluctuations
• Most dose adjustments should alter the total weekly dose by 5-20% 3
• Consider using validated decision support tools for dosing decisions 1

Special Considerations

High-Risk Patients

For patients at high risk of thromboembolism (mechanical heart valves, recent VTE, atrial fibrillation with prior stroke):

• More aggressive management may be warranted
• Consider more frequent INR monitoring
• Evaluate the need for bridging therapy on a case-by-case basis

Factors Contributing to Subtherapeutic INR

Common causes of subtherapeutic INR include:

• Medication non-adherence - most common cause 4
• Dietary changes (increased vitamin K intake)
• Drug interactions (enzyme inducers)
• Malabsorption or diarrheal illness
• Hypermetabolic states (hyperthyroidism, fever)

Monitoring Recommendations

• For patients with consistently stable INRs, testing frequency can be extended up to 12 weeks 1
• For patients with fluctuating INRs, more frequent monitoring is necessary
• Consider systematic and coordinated anticoagulation management services for improved outcomes 1

Pitfalls and Caveats

• Avoid routine bridging therapy for single subtherapeutic INR values, as this practice is not supported by evidence and may increase bleeding risk 1
• Avoid excessive dose adjustments for minor INR fluctuations, as this can lead to INR instability 5
• Do not use loading doses to rapidly correct subtherapeutic INR, as this may increase the risk of supratherapeutic anticoagulation 6
• Poor adherence to warfarin therapy is significantly associated with subtherapeutic INR (adjusted odds ratio = 6.13) 4

By following these evidence-based recommendations, clinicians can effectively manage patients with subtherapeutic INR while minimizing the risks of both thromboembolism and bleeding complications.