How should warfarin dosing be adjusted based on the current INR for a patient on warfarin (e.g., atrial fibrillation, venous thromboembolism, or mechanical heart valve)?

Warfarin Dose Adjustment Based on INR Levels

For stable patients on warfarin, adjust the weekly dose by 5-20% when INR falls outside the therapeutic range of 2.0-3.0, avoiding dose changes for single INR values between 1.7-3.3, and reserve vitamin K for INR >5.0 without bleeding or any INR with active bleeding. 1, 2

Target INR Ranges by Indication

• Atrial fibrillation and venous thromboembolism (DVT/PE): Target INR 2.0-3.0 (optimal 2.5) 3, 4, 5
• Bileaflet mechanical aortic valves: Target INR 2.0-3.0 6
• Mechanical mitral valves or older valve types: Target INR 2.5-3.5 6, 5
• Maximum efficacy requires INR >2.0, though some benefit persists at INR 1.5-1.9 1, 5

Maintenance Dose Adjustments for Stable Patients

Subtherapeutic INR (No Bleeding)

INR Range	Action	Citation
1.1-1.4	Increase weekly dose by ~20%	[1]
1.5-1.9	Increase weekly dose by ~10%	[1]

• Investigate causes: medication non-adherence, increased dietary vitamin K, drug interactions (especially enzyme inducers), gastrointestinal losses, or intercurrent illness 1, 6
• Do not administer vitamin K for subtherapeutic INR—vitamin K is only indicated for elevated INR 6
• Bridging anticoagulation with LMWH is rarely needed except for very high-risk patients (mechanical mitral valve, thromboembolism within 3 months, or history of thromboembolism while anticoagulated) 6

Mildly Supratherapeutic INR (No Bleeding)

INR Range	Action	Citation
3.1-3.5	Decrease weekly dose by ~10%	[1]
3.6-4.9	Hold warfarin until INR <3.5, restart at 10-15% lower weekly dose	[1]

• Do not administer vitamin K for INR <5.0 without bleeding 1, 7
• A single INR of 3.1 requires no intervention—continue current dose and recheck in 1-2 weeks 1
• Clinically significant bleeding risk does not rise appreciably until INR exceeds 3.5-5.0 1, 5

Significantly Elevated INR Without Bleeding

INR 5.0-9.0:

• Withhold warfarin for 1-2 doses and monitor serial INR determinations 3, 1, 7
• Add oral vitamin K 1-2.5 mg only if high bleeding risk factors present: age >65-75 years, prior bleeding history, concurrent antiplatelet therapy, renal failure, or alcohol use 1, 7
• Randomized trials show vitamin K accelerates INR normalization but does not reduce major bleeding (2% vs 0.8% with placebo over 1-3 months) 1

INR >9.0-10.0:

• Immediately stop warfarin and administer oral vitamin K 2.5-5 mg 1, 7
• Recheck INR within 24 hours 1

Management of Active Bleeding

Major Bleeding (Hemoglobin Drop ≥2 g/dL or Critical Site)

Immediate reversal protocol:

• Administer 4-factor prothrombin complex concentrate (PCC) 25-50 U/kg IV plus vitamin K 5-10 mg by slow IV infusion over 30 minutes, targeting INR <1.5 1, 8

PCC dosing algorithm based on INR:

INR Range	PCC Dose
2.0-3.9	25 U/kg IV
4.0-6.0	35 U/kg IV
>6.0	50 U/kg IV

1, 8

• PCC achieves INR correction within 5-15 minutes versus hours with fresh frozen plasma 1, 8
• Vitamin K must be co-administered because factor VII in PCC has only a 6-hour half-life 1, 8
• Fresh frozen plasma should only be used if PCC is unavailable 8

Minor Bleeding or Non-Critical Sites

• Stop warfarin and administer vitamin K 5-10 mg IV by slow infusion over 30 minutes 1
• Consider adding PCC if bleeding occurs at critical sites (intracranial, intraspinal, intraocular, pericardial, retroperitoneal) or patient is hemodynamically unstable 1, 8

Monitoring Schedule

• During initiation: Check INR daily until stable (typically 5-7 days), then 2-3 times weekly for 1-2 weeks 1
• First month: Weekly INR checks 3, 1
• After stability: Monthly INR monitoring once therapeutic range maintained for >70% of time 3
• After dose adjustment: Recheck INR within 3-7 days 1

Critical Pitfalls to Avoid

• Never exceed 10 mg vitamin K—higher doses create a prothrombotic state and prevent re-warfarinization for days 1, 8
• Avoid aggressive dose escalation after a single low INR—clinicians should be cautious about increasing doses when INR is spuriously low 9
• Do not change warfarin dose for single INR values between 1.7-3.3 in stable patients—this avoids unnecessary dose cycling and improves time in therapeutic range 2
• Anaphylactoid reactions occur in 3 per 100,000 IV vitamin K doses—always administer by slow infusion over 30 minutes 1, 8
• Maintain time in therapeutic range (TTR) >65-70% as the primary goal—poor INR control is an independent predictor of complications 3

Special Populations

• Elderly patients (>75 years) or frail individuals: Start with 2-4 mg daily; typically require maintenance doses <5 mg daily 1, 7
• Mechanical valve patients with supratherapeutic INR: Use low-dose vitamin K (1-2 mg) to avoid difficulty achieving therapeutic INR post-procedure and consider bridging anticoagulation 1, 8
• After bleeding episode: Do not restart warfarin until bleeding is completely controlled, source identified and treated, patient hemodynamically stable, and indication for anticoagulation still exists 1, 8