Macrocomplexes and discordant high-sensitivity cardiac troponin concentrations

Background Analytical comparisons between different high-sensitivity cardiac troponin (hs-cTn) assays are important for reassurance of results performed with different methodologies and to identify potential interferences or confounders to result interpretation. Our objective in the present study was to compare Beckman Coulter’s latest hs-cTnI assay to Abbott’s hs-cTnI assay and to assess agreement between results. Methods Two hundred ethylenediaminetetraacetic acid plasma samples that had clinically reported hs-cTnI results from the Abbott ARCHITECTi2000 that spanned the analytical range were stored (median = 4 h), re-centrifuged and retested for hs-cTnI on the Abbott ARCHITECTi1000 and Beckman Coulter Access2 analysers. Passing–Bablok regression and fold-differences were evaluated, with differences approximately three-fold between results further subjected to Roche hs-cTnT testing and polyethylene glycol precipitation. Results The Beckman and Abbott hs-cTnI concentrations were correlated ( r = 0.95) with Beckman yielding proportionally lower concentrations (slope = 0.78; 95%CI: 0.74–0.85). There were 12 samples that yielded Abbott hs-TnI concentrations ≥3-fold higher than the Beckman hs-cTnI concentrations; of which nine samples from seven different patients had sufficient quantity for additional testing. All seven patients had macrocomplexes as determined with polyethylene glycol precipitation that affected the Abbott hs-cTnI assay. One patient with Abbott hs-cTnI results >1300 ng/L had polyethylene glycol, heterophile antibodies and creatine kinase-MB testing performed which confirmed that a macrocomplex most likely affected the Abbott and Roche (hs-cTnT = 65 ng/L) assays but not the Beckman (hs-cTnI = 12 ng/L) assay. Conclusion The hs-cTnI concentrations obtained from ethylenediaminetetraacetic acid plasma between the Beckman and Abbott assays are highly correlated, with large differences in concentrations (≥3-fold) between Abbott and Beckman assays possible due to macrocomplexes.

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False-Positive AxSYM Cardiac Troponin I Results in a 53-Year-Old Woman

Archives of Pathology & Laboratory Medicine ◽

10.5858/2002-126-0606-fpacti ◽

2002 ◽

Vol 126 (5) ◽

pp. 606-609

Author(s):

Ronald J. Knoblock ◽

Christopher M. Lehman ◽

Ruth A. Smith ◽

Fred S. Apple ◽

William L. Roberts

Keyword(s):

Polyethylene Glycol ◽

Rheumatoid Factor ◽

Cardiac Troponin ◽

Troponin I ◽

Protein A ◽

Cardiac Troponin I ◽

Heterophile Antibody ◽

Clinically Significant ◽

Polyethylene Glycol Precipitation ◽

Number Of Classes

Abstract A number of classes of endogenous antibodies, including heterophile, rheumatoid factor, and autoantibodies, can interfere with immunoassay measurements of many different analytes. Heterophile and rheumatoid factor antibody interferences have been described previously for the AxSYM cardiac troponin I assay. Several commercial products have been developed to neutralize heterophile antibody interferences. We describe a patient with multiple apparently falsely elevated cardiac troponin I results that were unique to the AxSYM analyzer. These cardiac troponin I results diluted linearly. When treated with 2 different heterophile-blocking reagents, the magnitudes of the falsely elevated results increased 17- and 26-fold, and these results also demonstrated dilution linearity. This interfering substance could be removed by passage through an immobilized protein A column and by polyethylene glycol precipitation. It does not appear to be a classic heterophile antibody, nor is it a paraprotein. Laboratorians must remain constantly vigilant for immunoassay interferences that lead to clinically significant inaccurate results and must recognize that accepted methods for detecting and neutralizing the interference may be ineffective.

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Release Kinetics of Cardiac Biomarkers in Patients Undergoing Transcoronary Ablation of Septal Hypertrophy

Clinical Chemistry ◽

10.1373/clinchem.2011.178129 ◽

2012 ◽

Vol 58 (6) ◽

pp. 1049-1054 ◽

Cited By ~ 30

Author(s):

Christoph Liebetrau ◽

Helge Möllmann ◽

Holger Nef ◽

Sebastian Szardien ◽

Johannes Rixe ◽

...

Keyword(s):

Cardiac Troponin ◽

Troponin T ◽

Release Kinetics ◽

High Sensitivity ◽

Cardiac Biomarkers ◽

Fourth Generation ◽

Cardiac Troponin T ◽

Creatine Kinase Mb ◽

Septal Hypertrophy ◽

Kinetics Of

Abstract BACKGROUND The release kinetics of cardiac troponin T measured with conventional vs high-sensitivity cardiac troponin T (hs-cTnT) assays in patients with acute myocardial infarction (AMI) is difficult to establish. METHODS We analyzed the release kinetics of cTnT measured by fourth generation and high-sensitivity assays, creatine kinase-MB (CK-MB), and myoglobin in patients with hypertrophic obstructive cardiomyopathy undergoing transcoronary ablation of septal hypertrophy (TASH), a model of AMI. Consecutive patients (n = 21) undergoing TASH were included. Serum and EDTA-plasma samples were collected before and at 15, 30, 45, 60, 75, 90, and 105 min, and 2, 4, 8, and 24 h after TASH. RESULTS cTnT concentrations measured by the hs assay were significantly increased at 15 min [21.4 ng/L, interquartile range (IQR) 13.3–39.7 ng/L vs 11.3 ng/L, IQR 6.0–18.8 ng/L at baseline; P = 0.031]. In comparison, cTnT concentrations measured by the conventional fourth generation assay increased significantly at 60 min (30.0 ng/L, IQR 20.0–30.0 ng/L vs <10.0 ng/L, IQR <10.0–10.0 ng/L; P < 0.01), CK-MB at 90 min (8.4 μg/L, IQR 6.9–14.4 μg/L vs 0.9 μg/L, IQR 0.4–1.1 μg/L; P < 0.01), and myoglobin at 30 min (188.0 μg/L, IQR 154.0–233.0 μg/L vs 38.0 μg/L, IQR 28.0–56.0; P < 0.01). CONCLUSIONS cTnT concentrations measured by the hs assay were significantly increased after TASH at all of the time points, with a doubling at 15 min after induction of AMI, confirming earlier evidence of myocardial injury compared to the fourth generation cTnT assay and CK-MB and myoglobin.

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Disagreement between Cardiac Troponin Tests Yielding a Higher Incidence of Myocardial Injury in the Emergency Setting

Journal of Cardiovascular Development and Disease ◽

10.3390/jcdd8030031 ◽

2021 ◽

Vol 8 (3) ◽

pp. 31

Author(s):

Peter A. Kavsak ◽

Shawn E. Mondoux ◽

Janet Martin ◽

Mark K. Hewitt ◽

Lorna Clark ◽

...

Keyword(s):

Cardiac Troponin ◽

Myocardial Injury ◽

Ethylenediaminetetraacetic Acid ◽

High Sensitivity ◽

Clinical Diagnostics ◽

Emergency Setting ◽

Analytical Sensitivity ◽

Edta Plasma ◽

Ortho Clinical Diagnostics

Differences in patient classification of myocardial injury between high-sensitivity cardiac troponin (hs-cTn) assays have largely been attributed to assay design and analytical sensitivity aspects. Our objective was to compare Ortho Clinical Diagnostics’ (OCD) hs-cTnI assay to OCD’s contemporary/conventional assay (cTnI ES) and another hs-cTnI assay (Abbott hs-cTnI) in samples obtained from different emergency departments (EDs). Two different sample types were evaluated (lithium heparin and ethylenediaminetetraacetic acid (EDTA) plasma) in a non-selected ED population (study 1, n = 469 samples) and in patients for which ED physicians ordered cardiac troponin testing (study 2, n = 1147 samples), from five different EDs. The incidence of injury in study 1 was higher with the OCD hs-cTnI assay (30.9%; 95% CI: 26.9 to 35.2) compared to that of the Abbott hs-cTnI (17.3%; 95% CI: 14.1 to 21.0) and the OCD cTnI ES (15.4%; 95% CI: 12.4 to 18.9) assays, with repeat testing identifying 4.8% (95% CI: 3.0 to 7.5) of the OCD hs-cTnI results with poor reproducibility. In study 2, 4.6% (95% CI: 3.5 to 6.0) of the results were not reported for the OCD hs-cTnI assay (i.e., poor reproducibility) with 12.7% (95%CI: 8.7 to 17.8) of the OCD hs-cTnI results positive for injury being negative for injury with the Abbott hs-cTnI assay. In summary, the OCD hs-cTnI assay yields higher rates of biochemical injury with a higher rate of poor reproducible results in different ED populations.

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Discrepancy between Cardiac Troponin Assays Due to Endogenous Antibodies

Clinical Chemistry ◽

10.1093/clinchem/hvz032 ◽

2020 ◽

Vol 66 (3) ◽

pp. 445-454 ◽

Cited By ~ 3

Author(s):

Leo Lam ◽

Lisa Aspin ◽

Robert Campbell Heron ◽

Leah Ha ◽

Campbell Kyle

Keyword(s):

Regression Analysis ◽

Polyethylene Glycol ◽

Cardiac Troponin ◽

Protein A ◽

Gel Filtration ◽

Interquartile Range ◽

Clinical Use ◽

Gel Filtration Chromatography ◽

Polyethylene Glycol Precipitation

Abstract Background Despite well-described analytical effects of autoantibodies against cardiac troponin (cTn) I on experimental assays, no study has systematically examined their impact on cTn assays in clinical use. We determined the effects of endogenous antibodies on 5 different cTnI assays and a cTnT assay. Methods cTn was measured by 6 methods: Siemens hs-cTnI Centaur, Siemens hs-cTnI Vista, Abbott hs-cTnI Architect, Beckman hs-cTnI Access, Beckman cTnI Access, and Roche hs-cTnT Elecsys. Measurements were repeated on 5 assays (all except Siemens hs-cTnI Vista) following immunoglobulin depletion by incubation with protein A. Low recovery of cTnI (<40%) following immunoglobulin depletion was considered positive for macro-cTnI. Protein A findings were validated by gel filtration chromatography and polyethylene glycol precipitation. Results In a sample of 223 specimens selected from a community laboratory that uses the Siemens hs-cTnI Centaur assay and from which cTn was requested, 76% of samples demonstrated increased cTnI (median, 88 ng/L; interquartile range, 62–204 ng/L). Macro-cTnI was observed in 123 (55%) of the 223 specimens. Comparisons of cTnI assays markedly improved once patients with macro-cTnI were removed. Passing-Bablok regression analysis between hs-cTnI assays demonstrated different slopes for patients with and without macro-cTnI. In patients with macro-cTnI, 89 (72%) showed no effect on the recovery of cTnT, whereas 34 (28%) had reduced recovery of cTnT. The proportion of results above the manufacturers' 99th percentile varied with the cTn assay and macro-cTnI status. Conclusion We suggest that the observed discrepancy between hs-cTnI assays may be attributed in part to the presence of macro-cTnI.

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