Warfarin Dose Adjustment Based on INR Levels
Adjust warfarin dose using a structured algorithm: for INR 1.5-1.9 increase weekly dose by 10%, for INR 2.0-3.0 make no change, for INR 3.0-3.9 decrease by 10%, for INR 4.0-4.9 hold one dose then restart at 10% lower weekly dose, and for INR ≥5.0 hold until INR returns to 2-3 then restart at 15% lower weekly dose. 1
Target INR Range
- The therapeutic INR target is 2.0-3.0 for most indications including venous thromboembolism, atrial fibrillation, and most mechanical heart valves 2, 3
- For certain mechanical prosthetic valves (tilting disk, bileaflet in mitral position, or caged ball/disk valves), target INR is 3.0 (range 2.5-3.5) 3
- St. Jude Medical bileaflet valves in the aortic position require only INR 2.0-3.0 3
Dose Adjustment Algorithm for Established Therapy
The European Society of Cardiology provides the following structured approach 1:
| INR Range | Action |
|---|---|
| <1.5 | Increase weekly dose by 15% |
| 1.6-1.9 | Increase weekly dose by 10% |
| 2.0-2.9 | No change (therapeutic) |
| 3.0-3.9 | Decrease weekly dose by 10% |
| 4.0-4.9 | Hold 1 dose, restart at 10% lower weekly dose |
| ≥5.0 | Hold until INR 2-3, restart at 15% lower weekly dose |
Practical Implementation
- Calculate the total weekly warfarin dose, apply the percentage adjustment, then redistribute across the week 1
- For a single INR ≤0.5 below therapeutic range with previously stable values, continue current dose and retest within 1-2 weeks 1
- Avoid making multiple rapid dose adjustments, as this causes INR instability and overcorrection 4
Management of Elevated INR Without Bleeding
For INR 4.0-4.9: Hold one dose, then restart at weekly dose reduced by 10%, and recheck INR within 3-7 days 1, 5
For INR 5.0-9.0: Omit 1-2 doses, monitor closely, and resume at lower dose when INR approaches therapeutic range 1
For INR ≥9.0: Give oral vitamin K 3-5 mg, anticipating INR fall within 24-48 hours 1
Vitamin K Considerations
- Oral vitamin K is preferred over parenteral routes for non-urgent reversal due to predictable effectiveness and safety 1
- Vitamin K is only recommended for INR 4.0-4.9 if the patient has increased bleeding risk factors 4
- Avoid high-dose vitamin K (≥10 mg oral) as it causes warfarin resistance lasting up to one week 1
- For INR <5.0 without bleeding, routine vitamin K is not recommended as it causes unnecessary over-reversal 4
Management of Life-Threatening Bleeding
- Administer prothrombin complex concentrate supplemented with vitamin K 10 mg IV for life-threatening bleeding 1
- Fresh-frozen plasma is an alternative if prothrombin complex concentrate is unavailable 6
Initial Dosing Strategy
- Start warfarin at 2-5 mg daily, with lower doses (2-4 mg) for elderly or debilitated patients 3, 6
- Avoid loading doses, which increase hemorrhagic complications without providing more rapid protection 3, 7
- Overlap with therapeutic heparin for 4-5 days until INR is therapeutic for 2 consecutive days 2, 3
Monitoring Frequency
Initial phase: Check INR daily until stable in therapeutic range for 2 consecutive days, then 2-3 times weekly for 1-2 weeks 1
Stabilization phase: After 1-2 weeks, check weekly for 1 month 1
Maintenance phase: Once stable, extend monitoring intervals up to 4-6 weeks (or up to 12 weeks in consistently stable patients) 1, 3
After dose adjustment: Resume frequent monitoring (within 3-7 days) until INR stabilizes 5
Common Pitfalls to Avoid
- Do not overreact to minor INR deviations: A single slightly out-of-range INR in a previously stable patient does not require immediate dose change 1, 6
- Do not make rapid sequential adjustments: Allow 3-5 days between dose changes for the full anticoagulant effect to manifest 4, 6
- Investigate causes of INR elevation: Consider recent dietary changes (vitamin K intake), new medications (especially antibiotics, NSAIDs), alcohol consumption changes, and intercurrent illness 1, 5
- Avoid fixed-dose regimens: Considerable dose adjusting is required during maintenance to keep patients within range 8
Special Populations
Prosthetic heart valve patients: Exercise particular caution with dose adjustments, as these patients face high thromboembolism risk (≥4% annual cerebral embolism risk) if anticoagulation becomes subtherapeutic 5
Elderly patients: Use lower initial and maintenance doses due to increased sensitivity to warfarin 3, 6
Cancer patients: Maintain INR 2-3 for long-term VTE treatment, though LMWH is generally preferred over warfarin in this population 2