© 2010 American Association for Clinical Chemistry, Inc.
Clinical Case Study |
Commentary
Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine, St. Louis, MO.
Address correspondence to the author at: Department of Pathology and Immunology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine, 660 S. Euclid Ave., Box 8118, St. Louis, MO 63110. E-mail mscott{at}labmed.wustl.edu.
In the last decade, sensitive and specific immunoassays for cardiac troponins have revolutionized the diagnosis and management of cardiac disease. The absolute specificity of cardiac troponins for cardiac tissue and the sensitivity of the immunoassays have redefined risk stratification and treatments. The required sensitivity of these assays, however, has made the occurrence of false-positive cardiac troponin results an infrequent but very real laboratory problem. Any immunoassay has nonspecific background "noise," and the signal-to-noise ratio defines the sensitivity of the assay. In this regard cardiac troponin assays are particularly challenged because they must distinguish very small, but clinically significant, concentrations of cardiac troponin from "noise." Few immunoassays are asked to distinguish between "any antigen" and "none" (drug screens and human chorionic gonadotropin come to mind). Thus, unlike most immunoassays, additional "noise" in a cardiac troponin assay will be considered clinically important. Similarly, any small shift in the calibration of a cardiac troponin assay or lot-to-lot variation may cause an increase in the number of low but important cardiac troponin results. Indeed, multiple manufacturers have had to recall their cardiac troponin assays over the years because of false "low positive" values. Such small changes in the noise or baseline would not be clinically important or detected in most clinical immunoassays. For instance, a thyroid-stimulating hormone result of 1.2 µIU/mL vs a true concentration of 1.0 µIU/mL or a prostate-specific antigen result of 3.4 µg/L vs 3.1 µg/L would never be questioned. The authors mention clots as a cause of false-positive cardiac troponin values. We have found that the most common cause of false-positive cardiac troponin values in our laboratory is "dirty" samples (e.g., microclots, cells). False-positive results from these types of samples often are not repeatable, or the false signal can be eliminated by recentrifugation of the sample. When clinical decisions are made at the technical limits of an assay, the laboratory must be aware of the possibility of false-positive results and communicate with clinicians about their infrequent, but inevitable, occurrence. As ultrasensitive cardiac troponin assays debut in the next few years, this challenge is unlikely to go away.
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: Upon manuscript submission, all authors completed the Disclosures of Potential Conflict of Interest form. Potential conflicts of interest:
Employment or Leadership: None declared.
Consultant or Advisory Role: None declared.
Stock Ownership: None declared.
Honoraria: None declared.
Research Funding: M.G. Scott, Siemens Healthcare Diagnostics.
Expert Testimony: None declared.
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.
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