Abstract
Despite decades of experience with acetaminophen (APAP) overdoses, it remains unclear whether elevated hepatic transaminases or coagulopathy develop first. Furthermore, comparison of the predictive value of these two variables in determining hepatic toxicity following APAP overdoses has been poorly elucidated. The primary objective of this study is to determine the test characteristics of the aspartate aminotransferase (AST) and the prothrombin time (PT) in patients with APAP toxicity. A retrospective chart review of APAP overdoses treated with IV N-acetylcysteine at a tertiary care referral center was performed. Of the 304 subjects included in the study, 246 with an initial AST less than 1000 were analyzed to determine predictors of hepatic injury, defined as an AST exceeding 1000 IU/L. The initial AST >50 was 79.5 % sensitive and 82.6 % specific for predicting hepatic injury. The corresponding negative and positive predictive values were 95.5 and 46.3 %, respectively. In contrast, an initial abnormal PT had a sensitivity of 82.1 % and a specificity of 63.6 %. The negative and positive predictive values for initial PT were 94.9 and 30.2 %, respectively. Although the two tests performed similarly for predicting a composite endpoint of death or liver transplant, neither was a useful predictor. Initial AST performed better than the initial PT for predicting hepatic injury in this series of patients with APAP overdose.
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Rhyee SH, Farrugia L, Wiegand T, et al. The toxicology investigators consortium case registry—the 2012 experience. J Med Toxicol. 2013;9:380–404.
Mowry JB, Spyker DA, Cantilena Jr LR, et al. 2013 annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 31st annual report. Clin Toxicol. 2014;52:1032–283.
Hinson JA, Roberts DW, James LP. Mechanisms of acetaminophen-induced liver necrosis. Handb Exp Pharmacol. 2010;196:369–405.
Chun LJ, Tong MJ, Busuttil RW. Acetaminophen hepatotoxicity and acute liver failure. J Clin Gastroenterol. 2009;43:342–9.
Green TJ, Silvotti ML, Langmann C, et al. When do the aminotransferases rise after acute acetaminophen overdose. Clin Toxicol. 2010;48:787–92.
Hendrickson RG. Acetaminophen. In: Nelson LS, Hoffman RS, Lewin NA, et al., editors. Goldfrank’s toxicologic emergencies. 9th ed. New York: McGraw Hill Medical; 2011. p. 483–99.
Hanley JA, McNeil BJ. A method of comparing the areas under receiver operating characteristic curves derived from the same cases. Radiology. 1983;148:839–43.
Harrison PM, O’Grady JG, Keays RT, et al. Serial prothrombin time as prognostic indicator in paracetamol induced fulminant hepatic failure. BMJ. 1990;301:964–6.
O’Grady JG, Alexander GJ, Hayllar KM, et al. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology. 1989;97:439–45.
Van der Steeg J, Akhtar J, Burkhart KK, et al. Initial prothrombin time as a predictor of acetaminophen-induced hepatotoxicity. J Toxicol Clin Toxicol. 1995;33:508–9. abstract.
Van der Steeg J, DiSanto SK, Abendroth TW, et al. The effect of acetaminophen on the prothrombin time assay. J Toxicol Clin Toxicol. 1995;33:512. abstract.
Whyte IM, Buckley NA, Reith DM, et al. Acetaminophen causes an increased international normalized ratio by reducing functional factor VII. Ther Drug Monit. 2000;22:742–8.
Buckley NA, Dawson AH. Drug interactions with warfarin. Med J Aust. 1993;158:574–5.
Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a hemorrhagic risk factor in patients on warfarin. Br J Clin Pharmacol. 2005;59:371–4.
Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91:1621–7.
Parra D, Beckey NP, Stevens GR. The effect of acetaminophen on the international normalized ratio in patients stabilized on warfarin therapy. Pharmacotherapy. 2007;27:675–83.
Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term oral anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67:309–14.
Thijssen HH, Soute BA, Vervoot LM, et al. Paracetamol (acertaminophen) warfarin interaction: NAPQI, the toxic metabolite of paracetamol, is an inhibitor of enzymes in the vitamin K cycle. Thromb Haemost. 2004;92:797–802.
Gazzard BG, Henderson JM, Williams R. Early changes in coagulation following a paracetamol overdose and a controlled trial of fresh frozen plasma therapy. Gut. 1975;16:617–20.
Pizon AF, Jang DH, Wang HE. The in vitro effect of N-acetylcysteine on prothrombin time in plasma samples from healthy subjects. Acad Emerg Med. 2011;18:351–4.
Jang DH, Weaver MD, Pizon AF. In vitro study of N-acetylcysteine on coagulation factors in plasma samples from healthy subjects. J Med Toxicol. 2013;9:49–53.
Jepsen S, Hansen AB. The influence of N-acetylcysteine on the measurement of prothrombin time and activated partial thromboplastin time in healthy subjects. Scand J Clin Lab Invest. 1994;54:543–7.
Schmidt LE, Knudsen TT, Dalhoff K, et al. Effect of acetylcysteine on prothrombin index in paracetamol poisoning without hepatocellular injury. Lancet. 2002;360:1151–2.
Lucena MI, Lopez-Torres E, Verge C, et al. The administration of N-acetylcysteine causes a decrease in Prothrombin time in patients with paracetamol overdose but without evidence of liver impairment. Eur J Gastroenterol Hepatol. 2005;17:59–63.
Chuang J, Sadler MA, Witt DM. Impact of evacuated collection tube fill volume and mixing on routine coagulation testing using 2.5 ml (pediatric) tubes. Chest. 2004;126:1262–6.
Humphreys RE, McPhendran P. False elevation of partial thromboplastin time and prothrombin time. JAMA. 1970;214(9):1702–4.
Gilbert EH, Lowenstein SR, Koziol-McLain J, et al. Chart reviews in emergency medicine research: what are the methods? Ann Emerg Med. 1996;27:305–8.
Prescott LF, Park J, Ballantyne A, et al. Treatment of paracetamol (acetaminophen) poisoning with N-acetylcysteine. Lancet. 1977;2:432–4.
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Levine, M., O’Connor, A.D., Padilla-Jones, A. et al. Comparison of Prothrombin Time and Aspartate Aminotransferase in Predicting Hepatotoxicity After Acetaminophen Overdose. J. Med. Toxicol. 12, 100–106 (2016). https://doi.org/10.1007/s13181-015-0504-x
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DOI: https://doi.org/10.1007/s13181-015-0504-x