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Does This Patient Have Acute Myocardial Infarction?

Case Description

A 58-year-old female patient with a history of myocardial infarction (MI) [2] and multiple episodes of cardiomyositis presented with signs and symptoms of acute coronary syndrome (ACS). An electrocardiogram showed Q-waves that were attributed to her previous MI. Her first cardiac troponin I (cTnI) was <0.04 ng/mL but she progressed to ST-elevation acute MI while her cTnI remained <0.04 ng/mL for 69 h postadmission. cTnI by a different assay showed a rise and fall of cTnI concentration (Table 1).

Questions

1. What can cause false-negative cTn results in otherwise confirmed MI?

2. How can you prove a false-negative cTnI in this patient and determine the cause?

The answers are below.

Answers

False-negative results can be caused by posttranslational modification of an epitope of the cTn molecule or the presence of autoantibodies that block reagent--antibody binding in the immunoassay (1-3).

Testing using a cTnI assay from a different vendor can confirm the false-negative result (Table 1) and mixing studies can prove the presence of an anti-troponin autoantibody. In this case, mixing of the patient's samples with an interference-free patient pool, containing 0.32 ng/mL cTnI, confirmed the presence of blocking autoantibodies.

Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following3 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 or Potential Conflicts of Interest: No authors declared any potential conflicts of interest.

References

(1.) Panteghini M. Selection of antibodies and epitopes for cardiac troponin immunoassays: should we revise our evidence-based beliefs? Clin Chem 2005;51:803-4.

(2.) Eriksson S, Halenius H, Pulkki K, Hellman J, Pettersson K. Negative interference in cardiac troponin I immunoassays by circulating troponin autoantibodies. Clin Chem 2005;51:839-47.

(3.) Savukoski T, Twarda A, Hellberg S, Ristiniemi N, Wittfooth S, Sinisalo J, etal. Epitope specificity and IgG subclass distribution of autoantibodies to cardiac troponin. Clin Chem 2013;59:512-8.

Geza S. Bodor [1] *

[1] VA Eastern Colorado Health Care System, Pathology and Laboratory Medicine Service 113, Denver, CO.

* Address correspondence to the author at: University of Colorado, Denver, Department of Pathology, Aurora, CO 80045-0508. E-mail geza.bodor@ucdenver.edu.

Received September 20, 2016; accepted October 17, 2016.

DOI: 10.1373/clinchem.2016.265751

[2] Nonstandard abbreviations: MI, myocardial infarction; ACS, acute coronary syndrome; cTnI, cardiac troponin I.
Table 1. Patient's laboratory results (assay A) with results from the
comparison assay (assay B).

                          Neat sample,            50:50 Mix,
                             ng/mL              assay A, ng/mL

Time since admission,   Assay A   Assay B   Expected (a)   Measured
h:min

Admission                 0.0       0.0         0.16         0.0
1:49                      0.0     0.4 (b)       0.16         0.0
12:29                     0.0     7.3 (b)       0.16        QNS [c]
20:39                     0.0     5.7 (b)       0.16         0.0
44:40                     0.0     1.9 (b)       0.16         QNS
68:55                     0.0     1.1 (b)       0.16       Not done

                            50:50 Mix,
                          assay B, ng/mL

Time since admission,   Expected   Measured
h:min

Admission                 0.16       0.15
1:49                      0.36       0.25
12:29                     3.81       QNS
20:39                     3.01       3.14
44:40                     1.11       QNS
68:55                     0.71     Not done

(a) Expected concentrations were calculated from the measured cTnI
concentration in the neat sample and the concentration of the patient
pool (0.32 ng/mL).

(b) Positive for AMI.

[c] QNS, quantity notsufficient to do mixing study.
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Title Annotation:the Clinical Chemist: What Is Your Guess?
Author:Bodor, Geza S.
Publication:Clinical Chemistry
Date:Jan 1, 2017
Words:601
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