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In Vitro Study of N-acetylcysteine on Coagulation Factors in Plasma Samples from Healthy Subjects

  • Toxicology Investigation
  • Published:
Journal of Medical Toxicology Aims and scope Submit manuscript

Abstract

Introduction

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.

Method

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.

Discussion

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.

Conclusion

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.

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Acknowledgments

This study is supported in part by grant 5UL1RR029893 from the National Center for Research Resources, National Institutes of Health, the American Academy of Clinical Toxicology Research Award (Jang DH), and the Pittsburgh Emergency Medicine Foundation (PEMF).

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Authors and Affiliations

  1. Department of Emergency Medicine, Clinical and Translational Science Institute, New York University School of Medicine, New York, NY, USA

    David H. Jang

  2. Department of Emergency Medicine, Division of Medical Toxicology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Matthew D. Weaver & Anthony F. Pizon

  3. Robert C. Byrd Health Sciences Center, Charleston Division, West Virginia Poison Center, 3110 MacCorkle Ave., SE, Charleston, WV, 25304, USA

    Anthony F. Pizon

Authors
  1. David H. Jang
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  2. Matthew D. Weaver
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  3. Anthony F. Pizon
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Correspondence to David H. Jang.

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Jang, D.H., Weaver, M.D. & Pizon, A.F. In Vitro Study of N-acetylcysteine on Coagulation Factors in Plasma Samples from Healthy Subjects. J. Med. Toxicol. 9, 49–53 (2013). https://doi.org/10.1007/s13181-012-0242-2

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  • DOI: https://doi.org/10.1007/s13181-012-0242-2

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