How should I transition a patient on an unfractionated heparin (UFH) infusion to warfarin, taking into account age ≥ 70 years, weight < 70 kg, chronic liver disease, interacting medications (e.g., amiodarone, azole antifungals, macrolide antibiotics), thrombotic risk, and ability to swallow oral tablets?

Transitioning from Heparin Infusion to Warfarin

Initiate Warfarin Early with Appropriate Dosing

Start warfarin on day 1 or 2 of heparin therapy, using a reduced initial dose of 2-5 mg daily (not the standard 5 mg) given this patient's age ≥70 years, weight <70 kg, chronic liver disease, and interacting medications. 1

Specific Dosing Considerations

• For patients ≥70 years with weight <70 kg: Start with 2-3 mg daily, as elderly patients require approximately 1 mg/day less warfarin than younger individuals and demonstrate increased pharmacodynamic response 1, 2
• With chronic liver disease: Use lower starting doses (<5 mg daily) due to impaired warfarin metabolism and reduced synthesis of vitamin K-dependent clotting factors 1
• With amiodarone: Reduce warfarin dose by 30-50% as amiodarone significantly inhibits warfarin metabolism 1
• With azole antifungals or macrolide antibiotics: Anticipate need for 25-40% dose reduction and increase INR monitoring frequency to every 1-2 days during antibiotic therapy 1

Overlap Duration and Discontinuation Criteria

Continue UFH infusion for a minimum of 5 days AND until INR is ≥2.0 on two consecutive measurements taken more than 24 hours apart before discontinuing heparin. 1

Critical Overlap Requirements

• The 5-day minimum overlap is necessary because warfarin initially creates a paradoxical prothrombotic state by depleting protein C (half-life 6-8 hours) before depleting factors II, IX, and X (half-lives 24-72 hours) 1
• Only 20% of hospitalized patients actually meet this recommended guideline in real-world practice, representing a major quality gap 3
• Do not discontinue heparin based solely on achieving a single therapeutic INR, as this provides inadequate anticoagulation 1, 3

INR Monitoring Schedule

Monitor INR daily until stable therapeutic range (2.0-3.0) is achieved, then 2-3 times weekly for 1-2 weeks, then weekly for 1 month, then monthly thereafter. 1

Intensified Monitoring for High-Risk Patients

• Age ≥70 years: Requires more frequent monitoring due to increased INR fluctuations during illness and medication changes 1
• During antibiotic therapy: Check INR every 1-2 days as antibiotics commonly cause dramatic INR elevations 1, 2
• With liver disease: Monitor every 2-3 days initially, as hepatic dysfunction causes unpredictable warfarin response 1

Managing Inability to Swallow Oral Tablets

If the patient cannot swallow tablets, transition to subcutaneous UFH (250 U/kg every 12 hours) as a bridge to warfarin, which can be crushed and administered via feeding tube or dissolved in water. 1, 4

Alternative Bridging Strategy

• Fixed-dose subcutaneous UFH (approximately 250 U/kg every 12 hours, unmonitored) is safe and effective for VTE treatment and eliminates need for continuous IV access 1, 4
• This approach is particularly valuable when IV access is difficult or the patient is being discharged before achieving therapeutic INR 4
• Warfarin tablets can be crushed and mixed with small amounts of food or liquid without affecting absorption 1

Special Considerations for Thrombotic Risk

For patients with high thrombotic risk (recent VTE, mechanical mitral valve, atrial fibrillation with prior stroke), maintain more aggressive overlap with target aPTT 1.5-2.5 times control (anti-Xa 0.3-0.7 IU/mL) throughout the entire bridging period. 1

Risk Stratification

• High thrombotic risk: Requires full therapeutic anticoagulation throughout transition; consider extending overlap beyond 5 days if INR remains subtherapeutic 1
• Low thrombotic risk (VTE >3 months ago, atrial fibrillation without prior stroke): Standard 5-day overlap is sufficient 1

Critical Pitfalls to Avoid

• Never use loading doses (10 mg) in elderly, low-weight, or liver disease patients, as this frequently causes supratherapeutic INR and bleeding 1, 2, 5
• Do not discontinue heparin when INR first reaches 2.0—wait for two consecutive therapeutic INRs >24 hours apart 1, 3
• Avoid subcutaneous LMWH if creatinine clearance <30 mL/min, as accumulation occurs; use UFH instead 1
• Do not target INR >3.0, as this provides no additional efficacy and exponentially increases bleeding risk, particularly intracranial hemorrhage 2, 6
• Recognize that therapeutic aPTT on heparin does not guarantee sustained anticoagulation—only 29% of patients maintain therapeutic aPTT on consecutive measurements, requiring frequent dose adjustments 3

Practical Algorithm Summary

1. Day 1: Start UFH infusion (80 U/kg bolus, 18 U/kg/hour) AND warfarin 2-3 mg PO daily 1
2. Days 1-5: Maintain therapeutic aPTT 1.5-2.5 times control; check INR daily 1
3. Day 5+: Continue heparin until INR ≥2.0 on two consecutive days (>24 hours apart) 1
4. Discontinue heparin only after both criteria met (≥5 days AND two therapeutic INRs) 1
5. Reduce warfarin dose by 30-50% if amiodarone present; by 25-40% if azoles/macrolides added 1