How many doses of Sintrom (Acenocoumarol) should be omitted when the International Normalized Ratio (INR) is elevated at 4.7 with a target of 3?

Management of INR 4.7 with Target of 3.0 on Sintrom (Acenocoumarol)

For an INR of 4.7 with a target of 3.0, omit one dose of Sintrom, then resume at a dose reduced by approximately 10% of the weekly total. 1

Rationale for Single Dose Omission

An INR of 4.7 falls within the 4.0-4.9 range, which according to established dosing algorithms requires holding one dose followed by dose reduction. 1 This approach balances the need to reduce bleeding risk while avoiding excessive INR suppression that could increase thrombotic risk.

• The European Society of Cardiology's structured algorithm specifically recommends for INR 4.0-4.9: hold 1 dose, then restart with dose decreased by 10% per week. 1
• This represents a modest elevation of 1.7 units above target, which does not require aggressive reversal measures. 1

Why Not More or Fewer Doses?

Single dose omission is appropriate because:

• For INR values between 4.0-4.9 without bleeding, withholding warfarin and observation is the recommended management. 2
• Evidence shows that omitting a single dose of acenocoumarol effectively reduces INR in asymptomatic patients with INR values between 4.5-10.0. 3
• The American College of Chest Physicians found no major bleeding or thromboembolic events in patients with isolated INRs up to 4.4 who had minimal intervention. 4

Omitting multiple doses would be excessive because this INR level does not meet criteria for more aggressive management, which is reserved for INR ≥5.0. 1, 2

Vitamin K Considerations

Do not administer vitamin K for this INR level. 2

• Vitamin K is only recommended for INR 4.0-4.9 if the patient has increased bleeding risk factors. 2
• Research specifically on acenocoumarol shows that 1 mg oral vitamin K results in excessive over-reversal, with 36.6% of patients achieving sub-therapeutic INR levels. 3
• High-dose vitamin K can cause warfarin resistance lasting up to one week. 1, 2

Dose Adjustment Upon Resumption

When restarting Sintrom after the single omitted dose:

• Reduce the weekly total dose by 10%. 1
• For example, if the patient was taking 12 mg per week (e.g., 2 mg × 6 days), reduce to approximately 10.8 mg per week. 1
• This can be achieved by reducing individual daily doses proportionally across the week. 1

Monitoring Schedule

Recheck INR within 24-48 hours after the intervention. 2

• This timing allows confirmation that INR is decreasing appropriately. 2
• Continue more frequent monitoring (2-3 times weekly) until INR stabilizes within therapeutic range for at least two consecutive measurements. 1
• Once stable, gradually extend monitoring intervals. 4

Common Pitfalls to Avoid

• Do not make multiple dose adjustments in rapid succession, as this leads to INR instability and overcorrection. 4
• Do not use vitamin K routinely for INR <5.0 without bleeding, as it causes unnecessary over-reversal. 2, 3
• Do not continue the same dose without any adjustment, as the INR of 4.7 is significantly above target and requires intervention. 1
• Investigate potential causes of the elevated INR, including medication changes, dietary vitamin K intake variations, or compliance issues. 2

Special Considerations for Acenocoumarol

Acenocoumarol (Sintrom) has a shorter half-life than warfarin, which means:

• INR changes occur more rapidly with dose adjustments. 5
• The single dose omission will have a more immediate effect compared to warfarin. 3
• Genetic factors (VKORC1 and CALU polymorphisms) significantly influence acenocoumarol sensitivity, which may explain unexpected INR elevations. 5