Warfarin Dosing and Monitoring
Initial Dosing
Start warfarin at 2-5 mg daily for most patients, with 2-4 mg for elderly or high bleeding risk patients, and avoid loading doses. 1
Standard Initial Dose
- Begin with 5 mg daily for otherwise healthy patients, which produces satisfactory anticoagulation within 4-6 days 2, 1
- The FDA label explicitly states that large loading doses increase hemorrhagic complications without providing faster protection against thrombus formation 1
Lower Initial Doses for High-Risk Patients
- Use 2-4 mg daily for elderly, debilitated, or bleeding-prone patients 2, 1
- Consider lower doses for patients with genetic variations in CYP2C9 and VKORC1 enzymes 1
Alternative Higher-Dose Strategy (Outpatient Context)
- For otherwise healthy outpatients requiring rapid anticoagulation, 10 mg daily for 2 days followed by INR-guided adjustment achieves therapeutic range faster (4.2 vs 5.6 days) 3
- However, this approach causes more rapid protein C depletion, creating transient hypercoagulability, so concurrent heparin is mandatory 3
Concurrent Heparin Therapy
When rapid anticoagulation is needed, start warfarin on day 1-2 of heparin therapy and continue heparin for at least 4 days until INR is therapeutic for 2 consecutive days. 2, 3, 1
- Discontinue heparin only after INR reaches 2.0-3.0 for at least 2 consecutive measurements 3
- The anticoagulant effect of warfarin is delayed because it requires depletion of existing clotting factors 4
INR Monitoring Schedule
Initial Phase (Days 1-7)
- Check INR daily until therapeutic range (2.0-3.0) is achieved and sustained for 2 consecutive days 2, 1
- With 5 mg initial dosing, INR typically does not rise appreciably in the first 24 hours 5
Early Stabilization Phase (Weeks 1-2)
- Monitor INR 2-3 times weekly for 1-2 weeks after reaching therapeutic range 2, 1
- Adjust dose based on INR trends, not single aberrant values 5
Maintenance Phase (After Week 2)
- Gradually extend monitoring intervals up to every 4 weeks once INR remains stable 2, 1
- Maximum interval between tests should not exceed 4-6 weeks even with stable results 1, 5
Target INR Ranges by Indication
Standard Intensity (INR 2.0-3.0)
- Venous thromboembolism (DVT/PE) 1
- Atrial fibrillation (non-valvular) 1
- Bileaflet mechanical valve in aortic position 1
- Post-MI with moderate-intensity regimen 1
Higher Intensity (INR 2.5-3.5)
- Tilting disk or bileaflet mechanical valves in mitral position 1
- Caged ball or caged disk valves (plus aspirin 75-100 mg) 1
Very High Intensity (INR 3.0-4.0)
- Post-MI high-intensity regimen without aspirin (only in settings with meticulous INR monitoring) 1
Dose Adjustments
Principles of Adjustment
- Most maintenance doses range from 2-10 mg daily 1
- Adjust total weekly dose by 5-20% based on INR results 5
- Do not adjust for a single slightly out-of-range INR unless clinically significant 5
When INR is Subtherapeutic
- Increase weekly dose by 5-20% depending on how far below target 5
- Recheck INR in 3-7 days depending on degree of deviation 5
When INR is Supratherapeutic (but <5.0)
- Reduce weekly dose by 5-20% 5
- Hold 0-2 doses if INR significantly elevated 5
- Recheck INR in 3-7 days 5
Management of Elevated INR
INR 5.0-9.0 Without Bleeding
- Hold warfarin and consider oral vitamin K₁ 2.5 mg 5
- Resume at lower dose when INR approaches therapeutic range 5
INR >9.0 Without Bleeding
- Give oral vitamin K₁ 2.5-5 mg 5
- Monitor INR closely and resume warfarin at lower dose when appropriate 5
Any INR With Serious Bleeding
- Immediately give vitamin K₁ (IV) plus fresh frozen plasma or prothrombin complex concentrate 5
- This provides rapid reversal within hours rather than 6-12 hours with vitamin K alone 5, 6
Special Population: Pregnancy with Mechanical Valves
Low-Dose Warfarin (≤5 mg/day)
- Continuation throughout all 3 trimesters is reasonable after informed consent 4
- This carries lowest maternal risk but highest fetal risk (miscarriage, fetal death, congenital abnormalities) 4
High-Dose Warfarin (>5 mg/day)
- Switch to dose-adjusted LMWH (target anti-Xa 0.8-1.2 U/mL) during first trimester, then warfarin for trimesters 2-3 4
- If LMWH unavailable, use continuous IV UFH (aPTT 2× control) during first trimester 4
Peripartum Management
- Switch from warfarin to LMWH or UFH at least 1 week before planned delivery 4
- Switch from LMWH to UFH at least 36 hours before delivery 4
- Stop UFH at least 6 hours before vaginal delivery 4
Critical Pitfalls to Avoid
Bleeding Risk Factors
- INR >4.0 provides no additional benefit and substantially increases bleeding risk 1
- Bleeding risk increases exponentially above INR 3.0 6, 7
- Most bleeding complications occur early after initiation 4
- Elderly patients (>75 years) have highest risk of intracranial hemorrhage 7
Factors Causing INR Fluctuation
- Drug interactions (numerous medications affect warfarin metabolism) 1, 5
- Dietary vitamin K intake changes 4, 5
- Poor medication compliance 2
- Alcohol consumption 2
- Hepatic dysfunction and hypermetabolic states 6
Monitoring Failures
- Never extend monitoring beyond 4-6 weeks even with stable INR 1, 5
- A disproportionate number of thromboembolic and bleeding events occur when INR is outside therapeutic range 2
- Time in therapeutic range (TTR) should be ≥70% for optimal outcomes 7