In vitro study of N-acetylcysteine on coagulation factors in plasma samples from healthy subjects

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.

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.

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.

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.

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.