Acenocoumarol Dosing on Day 3 with Subtherapeutic INR
Continue acenocoumarol at 5 mg on day 3, as the expected maintenance dose for acenocoumarol is 3 mg daily, and an INR of 0.7 after only 2 days indicates insufficient time for therapeutic effect rather than inadequate dosing. 1
Rationale for Continuing Current Dose
Acenocoumarol has a plasma half-life of only 9 hours, which is significantly shorter than warfarin's 42-hour half-life, requiring 2-3 days for partial anticoagulant effect and 4-8 days for full therapeutic effect 1
The standard starting dose for acenocoumarol is 3 mg daily (compared to 5 mg for warfarin), and your patient is already receiving 5 mg, which exceeds the typical maintenance dose 1
An INR of 0.7 on day 3 is expected and does not indicate treatment failure, as vitamin K antagonists require several days to deplete existing clotting factors (particularly Factor II with its 60-hour half-life) before achieving therapeutic anticoagulation 1
Key Monitoring Principles
INR monitoring should be performed daily until the therapeutic range (2.0-3.0) is achieved, then transitioned to twice or three times weekly during the first 2 weeks 1
The INR value obtained on any given day reflects the dose administered 2 days prior, which is particularly important for acenocoumarol due to its short half-life 2
Patients typically achieve therapeutic INR within 5-7 days when started on appropriate maintenance doses 1, 3
Critical Pitfalls to Avoid
Do not increase the dose prematurely based on day 2-3 INR values, as this commonly leads to over-anticoagulation once the full effect manifests around days 4-8 1, 4
Avoid loading doses of oral anticoagulants, as they do not achieve therapeutic INR more rapidly than maintenance dosing and increase bleeding risk 1, 5
Be aware that patients with CYP2C9*3 genetic variants (present in 8-27% of populations) require significantly lower acenocoumarol doses (11.2 mg/week vs. 17.1 mg/week for wild-type) and are at higher risk for over-anticoagulation 6, 4
Specific Dosing Algorithm Moving Forward
Day 3: Continue 5 mg (current dose is already above standard maintenance) 1
Day 4: Check INR - if still subtherapeutic (<2.0), continue 5 mg; if approaching therapeutic range (1.5-2.0), consider reducing to 4 mg 1
Day 5-7: Daily INR monitoring with dose adjustments in 0.5-1 mg increments to achieve target INR 2.0-3.0 1
Ensure overlap with parenteral anticoagulation (UFH, LMWH, or fondaparinux) for at least 5 days AND until INR is 2.0-3.0 for two consecutive days 1
Special Considerations
Elderly patients, those with comorbidities, or those requiring very low warfarin doses may need longer time to achieve therapeutic INR and more conservative dosing adjustments 1
Acenocoumarol demonstrates greater INR fluctuation with uneven daily dosing compared to uniform daily doses, so maintain consistent daily dosing rather than alternating doses 2
The shorter half-life of acenocoumarol (9 hours) compared to warfarin (42 hours) means dose adjustments will manifest more quickly, requiring closer monitoring during titration 1, 7