Warfarin Dose Adjustment Based on INR Levels
For patients on established warfarin therapy with INR deviations, adjust doses systematically using a structured algorithm: increase weekly dose by 10-15% for subtherapeutic INRs, make no change for therapeutic INRs (2.0-3.0), decrease by 10% or hold doses for supratherapeutic INRs, with more aggressive interventions for INR ≥5.0. 1
Target INR Range
- Maintain INR between 2.0-3.0 (target 2.5) for most indications including venous thromboembolism, atrial fibrillation, and most mechanical heart valves 2, 3
- Higher intensity anticoagulation (INR 2.5-3.5) is recommended for specific mechanical valve types (tilting disk, bileaflet valves in mitral position, caged ball/disk valves) 3
Dose Adjustment Algorithm for Maintenance Therapy
Structured Approach Based on INR Values
For INR <1.5: Increase weekly warfarin dose by 15% 1
For INR 1.6-1.9: Increase weekly warfarin dose by 10% 1
For INR 2.0-2.9: Continue current dose without adjustment (therapeutic range for most indications) 1
For INR 3.0-3.9: Decrease weekly warfarin dose by 10% 1
For INR 4.0-4.9: Hold one dose, then restart with weekly dose decreased by 10% 1
For INR ≥5.0: Hold warfarin until INR returns to 2.0-3.0, then restart with weekly dose decreased by 15% 1
Management of Single Out-of-Range INR
- For a single INR ≤0.5 below or above therapeutic range in previously stable patients, continue the current dose and recheck INR within 1-2 weeks rather than making immediate dose adjustments 2, 4
- This approach is supported by evidence showing that immediate dose adjustments for minor INR deviations do not improve outcomes 4
- Do not routinely administer bridging heparin for single subtherapeutic INR values, as this increases bleeding risk without clear benefit 2, 4
Management of Elevated INR
INR >3.0 but <5.0 Without Bleeding
- Reduce dose or omit next dose, then resume at lower dose when INR approaches therapeutic range 1
INR 5.0-9.0 Without Bleeding
- Omit 1-2 doses and monitor closely 1
- Consider oral vitamin K 3-5 mg, anticipating INR reduction within 24-48 hours 1
INR ≥9.0 Without Bleeding
- Give oral vitamin K 3-5 mg 1
- Avoid high-dose vitamin K (≥10 mg oral) as it may cause warfarin resistance for up to one week 1
Life-Threatening Bleeding
- Administer prothrombin complex concentrate supplemented with vitamin K 10 mg IV 1
Monitoring Frequency
Initial Therapy
- Check INR daily until stable in therapeutic range for 2 consecutive days 1, 3
- Then check 2-3 times weekly for 1-2 weeks 1
- Then weekly for 1 month 1
Stable Maintenance Therapy
- For patients with consistently stable INRs, extend monitoring intervals up to 12 weeks rather than every 4 weeks 2, 4
- Acceptable intervals range from 1-4 weeks once stable dosage is established 3
After Dose Adjustments
- Resume frequent monitoring (within 1-2 weeks) after any dose change, during intercurrent illness, with medication changes, or with minor bleeding 1
Practical Dosing Considerations
- Most dose changes should alter the total weekly dose by 5-20% 5
- Most patients are maintained on 2-10 mg daily 3
- The anticoagulant effect persists beyond 24 hours, so missed doses should be taken the same day if remembered, but never doubled 3
- Computer-guided dosing algorithms may improve INR control compared to manual regulation, particularly for inexperienced providers 1
Common Pitfalls to Avoid
- Do not overreact to minor INR deviations with immediate dose changes when a single value is only slightly out of range 1, 4
- Avoid using high doses of vitamin K for INR reversal, which leads to prolonged warfarin resistance 1
- Do not routinely bridge with heparin for single subtherapeutic INR in stable patients 2, 4
- Ensure patients maintain consistent vitamin K intake, as fluctuations affect warfarin response 2
- Be aware of drug interactions, particularly with NSAIDs (including COX-2 inhibitors) and certain antibiotics, which should be avoided when possible 2