What to do with a patient on warfarin (Warfarin Sodium) 5 mg (milligrams) orally (PO) daily with a subtherapeutic International Normalized Ratio (INR) of 1.4?

Management of Subtherapeutic INR (1.4) on Warfarin 5 mg Daily

For a patient with INR 1.4 on warfarin 5 mg daily, increase the weekly warfarin dose by 10-20% (approximately 5.5-6 mg daily or alternating 5 mg and 6 mg doses) and recheck INR within 1-2 weeks. 1, 2

Rationale for Dose Adjustment

• An INR of 1.4 represents subtherapeutic anticoagulation for most indications (target INR 2.0-3.0), placing the patient at increased risk of thromboembolic events 3
• The American College of Chest Physicians (ACCP) guidelines suggest that for patients with previously stable therapeutic INRs who present with a single out-of-range INR of 0.5 below therapeutic, continuing the current dose is reasonable 1
• However, an INR of 1.4 is more than 0.5 below the lower therapeutic threshold of 2.0, warranting dose adjustment rather than observation alone 1, 2

Specific Dosing Algorithm

Weekly dose calculation:

• Current weekly dose: 5 mg × 7 days = 35 mg/week 2
• Recommended increase: 10-20% of weekly dose 2, 4
• New weekly dose: 35 mg × 1.10 to 1.15 = 38.5-40 mg/week 2

Practical implementation:

• Alternate between 5 mg and 6 mg daily (e.g., 5-6-5-6-5-6-5 pattern = 38 mg/week) 2
• Alternatively, give 5.5 mg daily if tablets can be split accurately 3

Critical Considerations Before Dose Adjustment

Investigate potential causes of subtherapeutic INR: 5, 4

• Medication non-adherence or missed doses
• New medications that induce warfarin metabolism (rifampin, carbamazepine, phenytoin)
• Increased dietary vitamin K intake
• Malabsorption or diarrheal illness
• Changes in thyroid function

Assess thrombotic risk stratification: 2

• High-risk conditions (mechanical heart valves, antiphospholipid syndrome, recurrent VTE) require more aggressive management 2, 3
• For antiphospholipid syndrome specifically, even an INR of 1.9 warrants prompt dose adjustment due to high thrombotic risk 2

Bridging Therapy Considerations

Bridging with heparin is NOT routinely recommended: 1

• The ACCP guidelines suggest against routinely administering bridging with heparin for patients with stable therapeutic INRs presenting with a single subtherapeutic INR value (Grade 2C) 1
• A retrospective study of 2,597 patients found no significant difference in thromboembolic events between low-INR and therapeutic-INR cohorts 1
• Exception: Consider bridging for very high-risk patients (e.g., mechanical mitral valve, recent thrombosis within 3 months) while awaiting therapeutic INR 1

Monitoring Strategy

INR recheck timing: 1, 2, 5

• Recheck INR within 1-2 weeks after dose adjustment 1, 2
• More frequent monitoring (within 3-5 days) may be warranted for high-risk thrombotic conditions 2
• Once stable, INR monitoring intervals can extend to 1-4 weeks 3

Follow-up assessment: 5, 4

• If INR remains subtherapeutic after dose adjustment, consider further 10-15% weekly dose increase 4
• If INR overshoots into supratherapeutic range, reduce dose by 10-20% 4

Common Pitfalls to Avoid

• Do not ignore a single subtherapeutic INR of 1.4, especially in high-risk patients, as this represents more than minimal deviation from therapeutic range 2
• Avoid excessive dose changes (>20% weekly) for INR 1.4, as this can cause INR instability and overshoot 2, 4
• Do not use loading doses to rapidly correct subtherapeutic INR, as this increases hemorrhagic complications without providing faster protection 3
• Do not assume warfarin resistance unless large daily doses (>10-15 mg) are consistently required to maintain therapeutic INR 3

Special Population Considerations

Elderly or debilitated patients: 3

• Consider more conservative dose increases (5-10% weekly) due to increased sensitivity to warfarin 3
• Lower maintenance doses (2-7 mg daily) are typical in elderly patients 3

Patients with genetic variations: 3

• CYP2C9 and VKORC1 polymorphisms affect warfarin metabolism and sensitivity 3
• These patients may require lower doses and more gradual adjustments 3