False positive acetaminophen concentrations in patients with liver injury

Julie Polson, Frank H. Wians, Paul Orsulak, Dwain Fuller, Natalie G. Murray, Jonathan M. Koff, Adil I. Khan, Jody A. Balko, Linda S. Hynan, William M. Lee

Research output: Contribution to journalArticle

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Abstract

Background: Acetaminophen toxicity is the most common form of acute liver failure in the U.S. After acetaminophen overdoses, quantitation of plasma acetaminophen can aid in predicting severity of injury. However, recent case reports have suggested that acetaminophen concentrations may be falsely increased in the presence of hyperbilirubinemia. Methods: We tested sera obtained from 43 patients with acute liver failure, mostly unrelated to acetaminophen, utilizing 6 different acetaminophen quantitation systems to determine the significance of this effect. In 36 of the 43 samples with bilirubin concentrations ranging from 1.0-61.5 mg/dl no acetaminophen was detectable by gas chromatography-mass spectroscopy. These 36 samples were then utilized to test the performance characteristics of 2 immunoassay and 4 enzymatic-colorimetric methods. Results: Three of four colorimetric methods demonstrated 'detectable' values for acetaminophen in from 4 to 27 of the 36 negative samples, low concentration positive values being observed when serum bilirubin concentrations exceeded 10 mg/dl. By contrast, the 2 immunoassay methods (EMIT, FPIA) were virtually unaffected. The false positive values obtained were, in general, proportional to the quantity of bilirubin in the sample. However, prepared samples of normal human serum with added bilirubin showed a dose-response curve for only one of the 4 colorimetric assays. Conclusions: False positive acetaminophen tests may result when enzymatic-colorimetric assays are used, most commonly with bilirubin concentrations > 10 mg/dl, leading to potential clinical errors in this setting. Bilirubin (or possibly other substances in acute liver failure sera) appears to affect the reliable measurement of acetaminophen, particularly with enzymatic-colorimetric assays.

Original languageEnglish (US)
Pages (from-to)24-30
Number of pages7
JournalClinica Chimica Acta
Volume391
Issue number1-2
DOIs
StatePublished - May 2008

Fingerprint

Acetaminophen
Liver
Bilirubin
Wounds and Injuries
Acute Liver Failure
Assays
Enzyme Assays
Serum
Immunoassay
Hyperbilirubinemia
Gas chromatography
Gas Chromatography
Toxicity
Mass Spectrometry
Spectroscopy
Plasmas

Keywords

  • Acetaminophen toxicity
  • Bilirubin
  • Colorimetric assay
  • Immunoassay

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry

Cite this

Polson, J., Wians, F. H., Orsulak, P., Fuller, D., Murray, N. G., Koff, J. M., ... Lee, W. M. (2008). False positive acetaminophen concentrations in patients with liver injury. Clinica Chimica Acta, 391(1-2), 24-30. https://doi.org/10.1016/j.cca.2008.01.018

False positive acetaminophen concentrations in patients with liver injury. / Polson, Julie; Wians, Frank H.; Orsulak, Paul; Fuller, Dwain; Murray, Natalie G.; Koff, Jonathan M.; Khan, Adil I.; Balko, Jody A.; Hynan, Linda S.; Lee, William M.

In: Clinica Chimica Acta, Vol. 391, No. 1-2, 05.2008, p. 24-30.

Research output: Contribution to journalArticle

Polson, J, Wians, FH, Orsulak, P, Fuller, D, Murray, NG, Koff, JM, Khan, AI, Balko, JA, Hynan, LS & Lee, WM 2008, 'False positive acetaminophen concentrations in patients with liver injury', Clinica Chimica Acta, vol. 391, no. 1-2, pp. 24-30. https://doi.org/10.1016/j.cca.2008.01.018
Polson J, Wians FH, Orsulak P, Fuller D, Murray NG, Koff JM et al. False positive acetaminophen concentrations in patients with liver injury. Clinica Chimica Acta. 2008 May;391(1-2):24-30. https://doi.org/10.1016/j.cca.2008.01.018
Polson, Julie ; Wians, Frank H. ; Orsulak, Paul ; Fuller, Dwain ; Murray, Natalie G. ; Koff, Jonathan M. ; Khan, Adil I. ; Balko, Jody A. ; Hynan, Linda S. ; Lee, William M. / False positive acetaminophen concentrations in patients with liver injury. In: Clinica Chimica Acta. 2008 ; Vol. 391, No. 1-2. pp. 24-30.
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abstract = "Background: Acetaminophen toxicity is the most common form of acute liver failure in the U.S. After acetaminophen overdoses, quantitation of plasma acetaminophen can aid in predicting severity of injury. However, recent case reports have suggested that acetaminophen concentrations may be falsely increased in the presence of hyperbilirubinemia. Methods: We tested sera obtained from 43 patients with acute liver failure, mostly unrelated to acetaminophen, utilizing 6 different acetaminophen quantitation systems to determine the significance of this effect. In 36 of the 43 samples with bilirubin concentrations ranging from 1.0-61.5 mg/dl no acetaminophen was detectable by gas chromatography-mass spectroscopy. These 36 samples were then utilized to test the performance characteristics of 2 immunoassay and 4 enzymatic-colorimetric methods. Results: Three of four colorimetric methods demonstrated 'detectable' values for acetaminophen in from 4 to 27 of the 36 negative samples, low concentration positive values being observed when serum bilirubin concentrations exceeded 10 mg/dl. By contrast, the 2 immunoassay methods (EMIT, FPIA) were virtually unaffected. The false positive values obtained were, in general, proportional to the quantity of bilirubin in the sample. However, prepared samples of normal human serum with added bilirubin showed a dose-response curve for only one of the 4 colorimetric assays. Conclusions: False positive acetaminophen tests may result when enzymatic-colorimetric assays are used, most commonly with bilirubin concentrations > 10 mg/dl, leading to potential clinical errors in this setting. Bilirubin (or possibly other substances in acute liver failure sera) appears to affect the reliable measurement of acetaminophen, particularly with enzymatic-colorimetric assays.",
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AU - Polson, Julie

AU - Wians, Frank H.

AU - Orsulak, Paul

AU - Fuller, Dwain

AU - Murray, Natalie G.

AU - Koff, Jonathan M.

AU - Khan, Adil I.

AU - Balko, Jody A.

AU - Hynan, Linda S.

AU - Lee, William M.

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N2 - Background: Acetaminophen toxicity is the most common form of acute liver failure in the U.S. After acetaminophen overdoses, quantitation of plasma acetaminophen can aid in predicting severity of injury. However, recent case reports have suggested that acetaminophen concentrations may be falsely increased in the presence of hyperbilirubinemia. Methods: We tested sera obtained from 43 patients with acute liver failure, mostly unrelated to acetaminophen, utilizing 6 different acetaminophen quantitation systems to determine the significance of this effect. In 36 of the 43 samples with bilirubin concentrations ranging from 1.0-61.5 mg/dl no acetaminophen was detectable by gas chromatography-mass spectroscopy. These 36 samples were then utilized to test the performance characteristics of 2 immunoassay and 4 enzymatic-colorimetric methods. Results: Three of four colorimetric methods demonstrated 'detectable' values for acetaminophen in from 4 to 27 of the 36 negative samples, low concentration positive values being observed when serum bilirubin concentrations exceeded 10 mg/dl. By contrast, the 2 immunoassay methods (EMIT, FPIA) were virtually unaffected. The false positive values obtained were, in general, proportional to the quantity of bilirubin in the sample. However, prepared samples of normal human serum with added bilirubin showed a dose-response curve for only one of the 4 colorimetric assays. Conclusions: False positive acetaminophen tests may result when enzymatic-colorimetric assays are used, most commonly with bilirubin concentrations > 10 mg/dl, leading to potential clinical errors in this setting. Bilirubin (or possibly other substances in acute liver failure sera) appears to affect the reliable measurement of acetaminophen, particularly with enzymatic-colorimetric assays.

AB - Background: Acetaminophen toxicity is the most common form of acute liver failure in the U.S. After acetaminophen overdoses, quantitation of plasma acetaminophen can aid in predicting severity of injury. However, recent case reports have suggested that acetaminophen concentrations may be falsely increased in the presence of hyperbilirubinemia. Methods: We tested sera obtained from 43 patients with acute liver failure, mostly unrelated to acetaminophen, utilizing 6 different acetaminophen quantitation systems to determine the significance of this effect. In 36 of the 43 samples with bilirubin concentrations ranging from 1.0-61.5 mg/dl no acetaminophen was detectable by gas chromatography-mass spectroscopy. These 36 samples were then utilized to test the performance characteristics of 2 immunoassay and 4 enzymatic-colorimetric methods. Results: Three of four colorimetric methods demonstrated 'detectable' values for acetaminophen in from 4 to 27 of the 36 negative samples, low concentration positive values being observed when serum bilirubin concentrations exceeded 10 mg/dl. By contrast, the 2 immunoassay methods (EMIT, FPIA) were virtually unaffected. The false positive values obtained were, in general, proportional to the quantity of bilirubin in the sample. However, prepared samples of normal human serum with added bilirubin showed a dose-response curve for only one of the 4 colorimetric assays. Conclusions: False positive acetaminophen tests may result when enzymatic-colorimetric assays are used, most commonly with bilirubin concentrations > 10 mg/dl, leading to potential clinical errors in this setting. Bilirubin (or possibly other substances in acute liver failure sera) appears to affect the reliable measurement of acetaminophen, particularly with enzymatic-colorimetric assays.

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KW - Colorimetric assay

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