UMEM Educational Pearls

Category: Toxicology

Title: Effect of N-Acetylcysteine on Prothrombin Time and Coagulation Factors

Keywords: acetylcysteine, NAC, INR, PT, prothrombin time (PubMed Search)

Posted: 6/12/2013 by Bryan Hayes, PharmD (Emailed: 6/13/2013) (Updated: 6/13/2013)
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In the treatment of acetaminophen poisoning with N-acetylcysteine (NAC), the PT/INR can be slightly elevated even in the absence of hepatotoxicity. Considering Prothombin Time (PT) is one of the criteria used to assess severity of liver damage in this setting, it is important to know how much the PT/INR can be affected by NAC and if it has an actual effect on coagulation factor levels.

  1. N-acetylcysteine has been shown to slightly increase the PT) by up to 3.5 seconds in healthy volunteers.
  2. A more recent study by the same authors demonstrated a reduction in vitamin K-dependent clotting factor activity (II, VI, IX, and X) after NAC administration in healthy volunteers.

Clinical Practice Pearls

  • The elevation in PT/INR after NAC administration is real, not simply laboratory interference.
  • However, the PT/INR elevation and decrease in coagulation factors is modest and not likely clinical signficant.
  • Many poison center guidelines allow for an INR up to 2 to be considered 'normal' to account for this phenomenon in this setting.


1. Pizon AF, et al. The in vitro effect of n-acetylcysteine on prothrombin time in plasma samples from healthy subjects. Acad Emerg Med 2011;18:351-4. [PMID 21496136]

2. Jang DH, et al. In vitro study of n-acetylcysteine on coagulation factors in plasma samples from healthy subjects. J Med Tox 2013;9:49-53. [PMID 22733602]

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