What to do with a patient with a subtherapeutic International Normalized Ratio (INR) of 0.7 after 2 days of 5mg daily acenocoumarol (nicoumalone)?

Management of Subtherapeutic INR 0.7 After 2 Days of Acenocoumarol 5mg Daily

Continue acenocoumarol 5mg daily and check INR on day 3 (tomorrow), as you are following standard initiation protocol and the INR of 0.7 after only 2 days is expected—therapeutic anticoagulation typically requires 4-5 days to achieve target INR of 2.0-3.0. 1

Understanding the Clinical Context

Your patient's INR of 0.7 after 2 days is not concerning—this is the normal trajectory during acenocoumarol initiation:

• Standard warfarin/acenocoumarol initiation protocols use 5-10mg daily for the first 2 days, with dose adjustments beginning on day 3 based on INR response 1
• The INR typically does not reach therapeutic range (2.0-3.0) until day 4-7 of treatment, with most patients requiring 4-5 days 1, 2
• Acenocoumarol has a shorter half-life than warfarin (8-11 hours vs 36-42 hours), but still requires several days to deplete existing vitamin K-dependent clotting factors 2

Immediate Management Plan

Day 3 Actions (Tomorrow)

• Check INR in the morning and adjust the acenocoumarol dose based on the result 1
• If INR remains <2.0 (which is expected), continue with individualized dosing between 1-10mg daily 1
• Do not give loading doses beyond the initial 2 days—this increases bleeding risk without improving time to therapeutic range 1

Bridging Anticoagulation Consideration

If your patient has high thromboembolic risk (mechanical heart valve, acute VTE, recent thromboembolism), you should have initiated bridging therapy with therapeutic-dose heparin or low-molecular-weight heparin (LMWH) from day 1:

• Standard unfractionated heparin: 80 IU/kg bolus, then 18 IU/kg/hour infusion targeting APTT 1.5-2.5 times control 1
• LMWH (dalteparin): 200 units/kg subcutaneously daily until INR reaches therapeutic range 3
• Discontinue heparin only after INR ≥2.0 for at least 24 hours (typically day 5-6) 1

If you have not started bridging and the patient is high-risk, initiate it now while continuing acenocoumarol 1, 3.

Monitoring Schedule

First Week Protocol

• Days 1-2: INR monitoring not required (you've completed this phase) 1
• Day 3: Check INR and adjust dose 1
• Days 4-7: Check INR every 1-2 days until therapeutic and stable 1
• Once INR is 2.0-3.0 for 2 consecutive measurements, discontinue bridging anticoagulation if used 1

Expected Timeline

• 50% of patients achieve therapeutic INR by day 5-7 using standard protocols 1
• Acenocoumarol may achieve therapeutic range slightly faster than warfarin due to shorter half-life, but the difference is modest 2, 4

Critical Pitfalls to Avoid

Do Not Increase Dose Prematurely

• Resist the urge to dramatically increase the dose based on day 2 INR—this leads to supratherapeutic INR by day 5-7 and increased bleeding risk 1, 2
• The relationship between dose and INR is non-linear and delayed—changes made today affect INR 2-3 days later 2

Do Not Use Vitamin K

• Never give vitamin K for subtherapeutic INR—it will create resistance to acenocoumarol and prevent therapeutic anticoagulation 5, 6
• Vitamin K is reserved exclusively for supratherapeutic INR (>4.0) or active bleeding 5, 2

Recognize Drug Interactions

• Antibiotics are the most common cause of acenocoumarol instability, particularly sulfamethoxazole-trimethoprim (24-fold increased risk of overanticoagulation) and amoxicillin-clavulanate 7
• If your patient starts antibiotics during initiation, increase INR monitoring frequency to every 1-2 days 7

Special Considerations for Acenocoumarol

Differences from Warfarin

• Acenocoumarol has shorter half-life (8-11 hours) compared to warfarin (36-42 hours), leading to more variable INR responses 2, 4
• Vitamin K is less effective for reversing acenocoumarol overanticoagulation compared to warfarin 2
• Patients with unstable anticoagulation on acenocoumarol may benefit from switching to warfarin (conversion factor 1.8), which improves time in therapeutic range from 40% to 60% 4

Pharmacogenetic Factors

• VKORC1, CYP2C9, CYP4F2, and ApoE polymorphisms significantly affect acenocoumarol dose requirements 8
• If your patient continues to have difficulty achieving therapeutic INR after 7-10 days, consider pharmacogenetic testing to guide dosing 8

When to Reassess Strategy

Contact a hematologist or anticoagulation specialist if:

• INR remains <1.5 after 7 days of therapy despite dose adjustments 1
• Patient develops bleeding complications at any INR level 1
• Thromboembolic event occurs during initiation phase 1
• Patient requires urgent surgery or procedure before achieving therapeutic INR 6