How is warfarin (coumarin) dose adjusted based on International Normalized Ratio (INR) levels?

Warfarin Dose Adjustment Based on INR Levels

For patients on established warfarin therapy with INR values outside the therapeutic range, adjust the weekly dose by 10-15% based on the degree of deviation: increase by 10-15% for INR <2.0, decrease by 10-15% for INR 4.0-5.0, and hold doses with vitamin K administration for INR ≥5.0. 1

Initial Dosing Strategy

• Start with 2-5 mg daily rather than loading doses, as loading doses increase hemorrhagic complications without providing faster therapeutic protection 2
• For elderly or debilitated patients, initiate at the lower end (2-4 mg daily) due to increased sensitivity 2, 3
• The INR will not rise appreciably in the first 24 hours except in rare patients requiring very small maintenance doses (0.5-2.0 mg) 3
• When rapid anticoagulation is needed, administer heparin concurrently for 4-5 days until INR is therapeutic for 2 consecutive days 4, 5

Target INR Ranges by Indication

• Most indications (venous thromboembolism, atrial fibrillation, bileaflet mechanical valve in aortic position): INR 2.0-3.0 2
• Mechanical mitral valves, tilting disk valves, or caged ball/disk valves: INR 2.5-3.5 2
• Post-myocardial infarction in settings with meticulous monitoring: INR 3.0-4.0 (high-intensity) or INR 2.0-3.0 with aspirin 2

Structured Dose Adjustment Algorithm for Maintenance Therapy

When INR is subtherapeutic:

• INR <1.5: Increase weekly dose by 15% 1
• INR 1.6-1.9: Increase weekly dose by 10% 1
• For a single INR ≤0.5 below range with previously stable values, continue current dose and retest in 1-2 weeks 1

When INR is therapeutic:

• INR 2.0-2.9 (or 2.0-3.0 depending on indication): No change needed 1

When INR is supratherapeutic:

• INR 3.0-3.9: Decrease weekly dose by 10% 1
• INR 4.0-4.9: Hold 1 dose, then restart with dose decreased by 10% per week 1
• INR ≥5.0: Hold warfarin until INR returns to 2-3, then restart with dose decreased by 15% per week 1

Most dose adjustments should alter the total weekly dose by 5-20%, and single INR values slightly out of range do not require immediate adjustment 3

Management of Elevated INR With or Without Bleeding

INR >therapeutic range but <5.0 without bleeding:

• Reduce dose or omit next dose, then resume at lower dose when INR approaches therapeutic range 4
• No vitamin K needed in most cases 4

INR 5.0-9.0 without bleeding:

• Low bleeding risk patients: Omit 1-2 doses, monitor closely, resume at lower dose 4
• High bleeding risk patients: Omit next dose AND give oral vitamin K 1.0-2.5 mg 4
• For rapid reversal (e.g., urgent surgery): Give oral vitamin K 2.0-5.0 mg, anticipating INR reduction within 24 hours 4

INR ≥9.0 without bleeding:

• Give oral vitamin K 3-5 mg, anticipating INR fall within 24-48 hours 4
• Monitor INR closely and repeat vitamin K as necessary 4

INR ≥20 or serious bleeding:

• Give vitamin K 10 mg by slow IV infusion (over 30 minutes) 4
• Administer fresh frozen plasma or prothrombin complex concentrate depending on urgency 4
• May require repeat vitamin K every 12 hours 4

Life-threatening bleeding:

• Prothrombin complex concentrate is indicated, supplemented with vitamin K 10 mg IV 4

Vitamin K Administration Routes and Doses

• Oral vitamin K is preferred for non-urgent reversal due to predictable effectiveness and safety advantages over parenteral routes 4
• Subcutaneous vitamin K has unpredictable and sometimes delayed response 4
• IV vitamin K produces rapid response but carries risk of anaphylaxis 4
• Avoid high-dose vitamin K (≥10 mg oral) as it may cause warfarin resistance for up to one week 4, 1

Monitoring Frequency

• Initial phase: Check INR daily until stable in therapeutic range for 2 consecutive days 4, 2
• Stabilization phase: Check 2-3 times weekly for 1-2 weeks 4, 2
• Maintenance phase: Check weekly for 1 month, then every 1-2 months if stable 4
• Maximum interval: Up to 4-6 weeks between tests for patients with consistently stable INR values 4, 3
• Resume frequent monitoring after any dose adjustment, during intercurrent illness, with medication changes, or with minor bleeding 4

Computer-Assisted Dosing

• Computer-guided warfarin dose adjustment may be superior to traditional manual dosing, particularly when personnel are inexperienced 4, 1
• Computerized algorithms achieve significantly better control when intensive therapy (INR 3.0-4.5) is required 4
• These systems require 50% fewer dose adjustments while maintaining comparable INR control 4

Critical Pitfalls to Avoid

• Do not overreact to minor INR deviations with immediate dose changes when a single value is slightly out of range 1, 3
• Avoid loading doses that raise INR excessively and increase bleeding risk without faster therapeutic protection 2, 3
• Do not use high-dose vitamin K (≥10 mg) for non-urgent INR reversal, as this causes prolonged warfarin resistance 4, 1
• Do not double doses to make up for missed doses; patients should take the missed dose as soon as remembered on the same day 2
• Bleeding risk increases sharply when INR exceeds 4.0, and INR >4.0 provides no additional therapeutic benefit 2