Management of Fluctuating INR After Sintrom (Acenocoumarol) Dose Adjustments
Resume Sintrom at a reduced daily dose of approximately 4.5 mg (alternating between 4 mg and 5 mg on alternate days) and recheck INR in 3-5 days, as the current situation reflects excessive dose adjustment followed by overcorrection from prolonged withholding.
Understanding the Current Clinical Scenario
Your patient demonstrates a classic pattern of INR instability from aggressive dose changes:
- Initial state: Stable at 2.5 on 4 mg daily (slightly below target of 3.0)
- First overcorrection: 25% dose increase (4→5 mg) caused supratherapeutic INR of 4.7
- Second overcorrection: 3-day complete withholding dropped INR to 0.7 (subtherapeutic)
- Current status: After 2 days of 5 mg, INR status unknown but likely rising
The INR of 0.7 after stopping for 3 days is unusually low and suggests either measurement error, patient non-adherence prior to the hold, or individual sensitivity to acenocoumarol withdrawal 1.
Immediate Management Steps
Resume Anticoagulation Now
Do not delay restarting therapy given the target INR of 3.0 suggests high-risk indication (likely mechanical heart valve or recurrent thromboembolism) 1.
Start with 4.5 mg daily (achieved by alternating 4 mg and 5 mg on alternate days), as this represents a modest 12.5% increase from the previously stable 4 mg dose 1.
The American Heart Association recommends that when anticoagulation is not urgent, treatment can commence with 4-5 mg daily, which typically produces satisfactory anticoagulation within 6 days 1.
Monitoring Schedule
Check INR in 3-5 days (not daily, as acenocoumarol has a shorter half-life than warfarin but still requires time to reach steady state) 1.
Once INR approaches therapeutic range (2.5-3.5), check 2-3 times weekly for 1-2 weeks, then weekly for 1 month 1.
The American College of Chest Physicians recommends daily monitoring until stable only during initial therapy, not during dose adjustments in established patients 1.
Key Principles for Dose Adjustments
Avoid Aggressive Changes
Small dose adjustments (10-15%) are preferred over large changes that led to this instability 1.
For a patient stable at INR 2.5 on 4 mg with target INR 3.0, the initial increase to 5 mg (25% increase) was excessive 1.
A more appropriate initial adjustment would have been 4.5 mg daily (12.5% increase) 1.
Duration of Withholding
Three days of complete withholding was excessive for an INR of 4.7 without bleeding 1.
The American Heart Association recommends for INR 5-9 without bleeding: omit only 1-2 doses and resume at lower dose when INR approaches therapeutic range 1.
For INR 4.7, omitting one dose and resuming at 4 mg would have been appropriate 1.
Special Considerations for Acenocoumarol (Sintrom)
Pharmacokinetic Differences from Warfarin
Acenocoumarol has a shorter half-life (8-11 hours) compared to warfarin (36-42 hours), leading to more rapid INR fluctuations 2.
The conversion factor between acenocoumarol and warfarin is approximately 1.8, meaning acenocoumarol is more potent milligram-per-milligram 2.
Patients on acenocoumarol may experience two-fold higher risk of unstable anticoagulation compared to warfarin 2.
Consider Switching to Warfarin
If instability persists despite careful dose adjustments, switching to warfarin may improve control 2.
A study of 68 patients with unstable acenocoumarol showed that switching to warfarin increased time in therapeutic range from 40.2% to 60.4% over 6 months 2.
Investigating Causes of Instability
Assess for Contributing Factors
Medication changes: New antibiotics, NSAIDs, or other interacting drugs 1.
Dietary changes: Fluctuations in vitamin K intake from green leafy vegetables 1.
Adherence issues: Confirm patient is taking medication as prescribed 1.
Intercurrent illness: Fever, diarrhea, or other acute conditions affecting absorption 1.
Alcohol consumption: Can potentiate anticoagulant effect 1.
Common Pitfalls to Avoid
Do Not Overreact to Single Values
Avoid making large dose changes based on single INR measurements, especially if previously stable 3.
The American College of Chest Physicians recommends that for single out-of-range INR ≤0.5 from target with previously stable values, continue current dose and retest in 1-2 weeks 3.
Do Not Use Vitamin K for INR 4.7 Without Bleeding
Vitamin K was not indicated for INR 4.7 without bleeding, as simple dose omission would have sufficed 1.
Vitamin K (1-2.5 mg orally) is recommended only when INR is 5-9 and patient has increased bleeding risk 1.
Using vitamin K can cause warfarin resistance and make subsequent dose adjustments more difficult 1.
Do Not Withhold for Extended Periods
Prolonged withholding (>2 days) for INR <10 without bleeding is excessive and creates rebound subtherapeutic anticoagulation 1.
For high-risk patients (target INR 3.0), even brief periods of subtherapeutic anticoagulation increase thrombotic risk 1.
Ongoing Management Strategy
Establish Stable Dosing
Once INR returns to 2.5-3.5 range, maintain that dose without further adjustments for at least 2 weeks to confirm stability 1.
Make only one dose change at a time and allow 5-7 days to assess full effect before further adjustments 1.