What adjustment is needed for a patient on Warfarin 10 mg daily with a subtherapeutic INR (International Normalized Ratio) of 1.9?

Warfarin Dose Adjustment for Subtherapeutic INR

For a patient on warfarin 10 mg daily with an INR of 1.9 (target 2-3), increase the total weekly warfarin dose by 10-20%, which translates to adding approximately 7-14 mg to the weekly total, and recheck the INR in 1-2 weeks. 1

Rationale for Dose Adjustment

• The American College of Chest Physicians recommends that dose adjustments are warranted when the INR deviates by more than 0.5 units from the therapeutic range, and since this patient's INR of 1.9 is only 0.1 units below target, a conservative approach is reasonable 1
• However, given the patient is on a relatively high daily dose (10 mg) and still subtherapeutic, this suggests either non-adherence, drug interactions, dietary factors, or individual pharmacogenetic variation requiring investigation 1
• The current INR of 1.9 represents minimal subtherapeutic anticoagulation that does not require bridging therapy with heparin, as bridging increases bleeding risk without clear benefit for single subtherapeutic readings 1

Specific Dosing Algorithm

• Increase the weekly dose by 10-15%, which means adding 7-10.5 mg to the current weekly total of 70 mg (10 mg × 7 days), resulting in a new weekly dose of 77-80.5 mg 2
• Practical implementation: Take 11 mg on 3 days per week and 10 mg on 4 days per week (total 73 mg/week), or 11 mg on 5 days and 10 mg on 2 days (total 75 mg/week) 2
• For patients requiring more aggressive adjustment, consider 12 mg on 2-3 days per week with 10 mg on remaining days 3

Monitoring Strategy

• Recheck INR in 1-2 weeks after implementing the dose increase, as this allows sufficient time for the new steady-state anticoagulation level to be achieved given warfarin's 40-hour half-life 1, 4
• Once INR stabilizes within the 2.0-3.0 target range, continue monitoring every 1-2 weeks initially, then gradually extend to every 4 weeks if consistently stable 1
• The target INR should remain 2.5 (range 2.0-3.0) for most indications including venous thromboembolism and atrial fibrillation 4, 5

Critical Factors to Investigate

• Medication adherence must be assessed first, as non-compliance is the most common cause of subtherapeutic INR in patients on established warfarin therapy 1
• Recent dietary changes affecting vitamin K intake (increased consumption of green leafy vegetables, nutritional supplements) can lower INR 1
• New medications or supplements that induce CYP2C9 metabolism (rifampin, carbamazepine, St. John's wort) reduce warfarin effect 1
• Intercurrent illness with diarrhea or vomiting may decrease warfarin absorption 6
• Consider CYP2C9 and VKORC1 genetic polymorphisms if the patient consistently requires unusually high doses, as patients with wild-type CYP2C9*1/*1 genotype have higher warfarin clearance 4

Common Pitfalls to Avoid

• Do not initiate bridging therapy with low-molecular-weight heparin for a single INR of 1.9, as this increases major bleeding risk without demonstrated benefit in reducing thromboembolic events 1
• A retrospective study of 2,597 patients showed no significant difference in thromboembolic events between patients with subtherapeutic INR and those with therapeutic INR, supporting the safety of omitting bridging 1
• Avoid excessive dose increases greater than 20% of the weekly total, as this can lead to supratherapeutic anticoagulation and increased bleeding risk 2, 3
• Do not make dose adjustments based solely on a single INR reading without considering clinical context and potential reversible causes 1
• Do not use loading doses or double doses to rapidly correct subtherapeutic INR, as warfarin's anticoagulant effect does not rise appreciably in the first 24 hours and excessive dosing increases bleeding risk 3

Special Considerations for High-Dose Requirements

• The current dose of 10 mg daily is higher than typical maintenance doses (mean 3-7 mg daily for most patients), suggesting this patient may have factors increasing warfarin metabolism 4
• Asian patients typically require lower doses (mean 3.3 mg daily), while this patient's requirement suggests Caucasian ancestry or specific genetic variants 4
• Elderly patients (≥60 years) typically exhibit greater INR response and require lower doses, so if this patient is elderly, the high dose requirement warrants investigation for non-adherence or drug interactions 4