What will the International Normalized Ratio (INR) be on day 3 after administering 5 mg of acenocoumarol (generic name) daily for 2 consecutive days with an initial INR of 0.7?

Predicting INR on Day 3 After Acenocoumarol Administration

Direct Answer

Your INR on day 3 will likely remain dangerously low (approximately 0.8-1.2), far below any therapeutic target, because an initial INR of 0.7 indicates either a severe underlying coagulopathy requiring immediate investigation, laboratory error, or non-vitamin K antagonist anticoagulant interference—not a condition that responds predictably to standard acenocoumarol dosing. 1

Critical Problem: INR 0.7 is Physiologically Abnormal

• An INR of 0.7 is below the normal reference range (0.8-1.2) and should not occur in patients without severe underlying pathology. 1
• This value suggests one of three scenarios that must be urgently investigated:
  • Laboratory error or specimen contamination (most common cause)
  • Severe vitamin K deficiency (malnutrition, malabsorption, prolonged antibiotic use)
  • Congenital factor deficiency (extremely rare in adults presenting for anticoagulation)
  • Interference from direct oral anticoagulants (dabigatran, rivaroxaban, apixaban) if patient was previously on these agents 1

Why Standard Dosing Predictions Don't Apply

• The European Society of Cardiology guidelines specify that acenocoumarol initiation should begin with 3 mg daily (not 5 mg) in patients with normal baseline coagulation. 1
• Your 5 mg daily dosing for 2 days represents a 67% higher dose than recommended, yet starting from INR 0.7 means you're not beginning from a normal physiologic baseline 1
• Acenocoumarol has a plasma half-life of only 9 hours, meaning steady-state effects require 3-5 days to manifest, and full therapeutic response typically takes 5-7 days. 1

Expected INR Trajectory (If No Underlying Pathology)

Based on pharmacokinetic principles and guideline data:

• Day 1 (after first 5 mg dose): INR likely 0.7-0.9 (minimal change due to short half-life) 1
• Day 2 (after second 5 mg dose): INR likely 0.8-1.1 (Factor VII begins declining first, half-life 6 hours) 1, 2
• Day 3 (your question): INR likely 0.9-1.3 (still subtherapeutic; Factor II has 60-hour half-life and determines full anticoagulant effect) 1
• Days 5-7: INR may reach 1.5-2.5 if no underlying pathology and continued dosing 1

Genetic Factors That Dramatically Alter Response

• Patients carrying the VKORC1 1173t variant (present in 27-40% of populations) achieve significantly higher INR values after 3 days of acenocoumarol: median INR 2.07 versus 1.74 in wild-type patients. 3
• Patients with both VKORC1 1173t and CALU a29809g variants (27% of one study population) achieved INR of 2.26 after 3 days and required 28% lower maintenance doses. 3
• However, these studies used the recommended 3 mg daily starting dose in patients with normal baseline INR, not your scenario 3

Immediate Actions Required

You must not continue empiric dosing without investigating the cause of INR 0.7:

1. Repeat INR measurement immediately using a different laboratory or point-of-care device to rule out laboratory error 1
2. Obtain complete coagulation panel: PT, aPTT, fibrinogen, Factor II, VII, IX, X levels 1
3. Assess for vitamin K deficiency: dietary history, recent antibiotic use (especially fluoroquinolones, cephalosporins), malabsorption symptoms 4
4. Review all medications for interactions: particularly antibiotics, antifungals, amiodarone, which can dramatically alter acenocoumarol metabolism 4
5. If patient was recently on direct oral anticoagulants, these can interfere with INR measurement and must clear completely (24-48 hours) before accurate INR assessment 1

Monitoring Strategy Once Pathology Excluded

• The European Society of Cardiology recommends daily INR monitoring until therapeutic range is achieved, then 2-3 times weekly for the first 2 weeks. 1, 5
• For patients requiring high target INR (3.0), consider bridging with therapeutic-dose low-molecular-weight heparin (100 U/kg subcutaneously every 12 hours) until INR reaches therapeutic range, as the thrombotic risk during subtherapeutic anticoagulation is substantial. 5

Common Pitfall to Avoid

Do not assume linear dose-response relationships with vitamin K antagonists. The relationship between dose and INR is highly variable between individuals due to genetic polymorphisms (CYP2C9, VKORC1), dietary vitamin K intake, drug interactions, and hepatic function 3, 6. A patient starting with INR 0.7 requires individualized investigation and monitoring, not algorithmic dose escalation 1.