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Related Experiment Videos

Acetaminophen causes an increased International Normalized Ratio by reducing functional factor VII.

I M Whyte1, N A Buckley, D M Reith

  • 1Department of Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital, New South Wales, Australia.

Therapeutic Drug Monitoring
|December 29, 2000
PubMed
Summary

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Acetaminophen overdose can cause a temporary increase in International Normalized Ratio (INR), especially at higher doses. N-acetylcysteine treatment appears to protect against this effect.

Area of Science:

  • Toxicology
  • Pharmacology
  • Hematology

Background:

  • Acetaminophen (APAP) can affect International Normalized Ratio (INR) in patients on anticoagulants or with APAP poisoning.
  • The precise impact of APAP on INR, particularly in non-hepatic injury poisoning, requires further investigation.

Purpose of the Study:

  • To investigate and describe the effect of acetaminophen poisoning on INR.
  • To explore the relationship between acetaminophen dose, nomogram-based risk, and INR elevation.
  • To identify potential protective factors and underlying mechanisms.

Main Methods:

  • Retrospective study of patients admitted to a toxicology center with acetaminophen poisoning.
  • Comparison of exposed (acetaminophen poisoning) and nonexposed (psychotropic drug poisoning) cohorts.

Related Experiment Videos

  • Measurement of INR, acetaminophen concentrations, and coagulation factors (VII, IX, VIIIc).

    • Main Results:

    • A time-dependent increase in INR was observed in acetaminophen poisoning cases.
    • Fifty percent of all patients and 66% with high acetaminophen levels showed abnormal INR.
    • Higher ingested dose and nomogram-based risk correlated with INR elevation; N-acetylcysteine showed a protective effect.
    • Reduced levels of functional Factor VII and Factor IX were noted in exposed patients.

    Conclusions:

    • Isolated, mild INR elevation is common in acetaminophen poisoning without liver injury.
    • The mechanism involves inhibition of Vitamin K-dependent coagulation factor activation.
    • This finding provides a potential explanation for acetaminophen's interaction with warfarin.