In vitro study of N-acetylcysteine on coagulation factors in plasma samples from healthy subjects.
BACKGROUND
In the treatment of acetaminophen toxicity, clinicians believe that N-acetylcysteine (NAC) artificially elevates prothrombin time (PT). However, the effect of NAC on human blood coagulation remains unverified. In a previous study, we show that NAC had a dose-dependent effect on PT. To our knowledge, there are no studies that specifically examine the mechanism by which NAC affects PT. This study evaluates the effect from a therapeutic NAC dose on the activity of coagulation factors II, VII, IX, and X in human plasma.


METHODS
We obtained blood samples from ten volunteer subjects. After centrifugation of each volunteer's blood sample, the plasma was pipetted and divided into two 1-mL aliquots. We used the first-1 mL sample as a control. The second 1-mL plasma sample had 5 μL of 20 % NAC, added to make a final concentration of 1,000 mg of NAC per L of plasma. This concentration of NAC approximates the plasma levels achieved after a 150-mg/kg dose. We incubated the two samples for each subject (control and 1,000 mg/L) at 37°C for 1 h and measured the activity of coagulation factors II, VII, IX, and X. We compared factor activity using the paired student t test.


RESULTS
Participants included ten healthy subjects; six males, four females, median age 31 years. Mean values of the control samples for factors II, VII, IX, and X were 134 (CI 119-149), 126 (CI 90-163), 137 (CI 117-157), and 170 (CI 144-196) %, respectively. Mean values of the NAC-containing samples for factors II, VII, IX, and X were 90 (CI 79-100), 66 (CI 51-80), 74 (CI 63-85), and 81 (CI 71-90) %, respectively. All samples containing NAC had significantly lower coagulation factor activity level than their controls with a p < 0.001.


CONCLUSIONS
In a previous study, we were able to demonstrate that NAC had a dose-dependent effect on PT. In this study, we compared activity of factors II, VII, IX, and X at baseline and for samples that received NAC. All factor activity had a significant decrease with the addition of NAC. This fall in factor activity is not explained by the dilution of adding NAC to the test samples.


CONCLUSIONS
We are able to demonstrate a significant decrease in the activity of coagulation factors II, VII, IX, and X with the addition of NAC. This may be the mechanism by which PT increased in our previous study.
Department of Emergency Medicine, Clinical and Translational Science Institute, New York University School of Medicine, New York, NY, USA. Jangd01@nyumc.org
David H
DH
Jang
Matthew D
MD
Weaver
Anthony F
AF
Pizon
D000111:Acetylcysteine / Q000494:pharmacology*; D000328:Adult; D000931:Antidotes / Q000494:pharmacology*; D001779:Blood Coagulation Factors / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011517:Prothrombin Time
D000931:Antidotes; D001779:Blood Coagulation Factors; D016166:Free Radical Scavengers; D000111:Acetylcysteine