© 2010 American Association for Clinical Chemistry, Inc.
Clinical Case Study |
Commentary
University of Maryland School of Medicine, Laboratories of Pathology, University of Maryland Medical Center, Baltimore, MD.
Address correspondence to the author at: University of Maryland School of Medicine, Laboratories of Pathology, University of Maryland Medical Center, 22 South Greene St., Baltimore, MD 21201. Fax 410-328-5880; e-mail rchristenson{at}umm.edu.
Serial quantitative measurements of cardiac troponin I or T have become the cornerstone for diagnosis of myocardial infarction (MI) and are useful for stratifying risk and guiding management of patients with suspected acute coronary syndrome(1). This clinical case reminds us that in addition to documenting values exceeding a specified cutpoint, a rise and/or fall in the biomarker is essential for establishing the diagnosis. Cardiac troponin is a marker of cardiac injury, not etiology. Many non-MI conditions may cause troponin increases, and analytical false positives are also possible. Although cardiac troponin measurements are central for assessment of patients with suspected acute coronary syndrome, MI is a clinical diagnosis, and other nonlaboratory data are essential.
The presence of antibodies that affect cardiac biomarker results was documented in the 1970s and 1980s, when antibodies to CK-BB were identified as an interference with some CK-MB methods. Antibodies against other species, e.g., HAMA, can cause a positive interference with immunoassay reagents for cardiac markers. Autoantibodies that react with cardiac troponin can cause either negative interference(2) or positive interference, as was seen in this case. An important point made in this case was that autoantibodies against cardiac troponin can occur in about 10% of healthy individuals. The common occurrence of such autoantibodies in healthy individuals compels us to be very thoughtful when establishing 99th percentile cutpoints for MI and risk assessment in reference control populations, as recommended in MI redefinition and guideline documents(1)(3).
Coronary heart disease remains the most common cause of death in the Western world, and approximately 6–9 million patients with suspected acute coronary syndrome present annually to emergency departments in the US alone. Given the central role of cardiac troponin measurements, laboratories should be prepared to investigate potential interferences by having on hand heterophile blocking tubes, stocking protein A columns, and/or arranging access to alternative cardiac troponin methods.
Acknowledgments
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
Authors’ Disclosures of Potential Conflicts of Interest: No authors declared any potential conflicts of interest.
Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript.
References
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[Free Full Text] - Eriksson S, Halenius H, Pulkki K, Hellman J, Pettersson K. Negative interference in cardiac troponin I immunoassays by circulating troponin autoantibodies. Clin Chem 2005;51:839-847.
[Abstract/Free Full Text] - Thygesen K, Alpert JS, White HD. Universal definition of myocardial infarction. J Am Coll Cardiol 2007;50:2173-2195.
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