Methods for analyzing positive cardiac troponin assay interference

Hammarsten, Ola; Becker, Charlotte; Engberg, Anna

doi:10.1016/j.clinbiochem.2023.03.004

Cited by 9 publications

(4 citation statements)

References 29 publications

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“…No interference was observed with numerous other immunometric assays such as Ferritin CEA, Ca19.9. CA125, CA15.3, Tropoinn T, BNP which always presented values within the normal reference ranges [21][22][23].…”

Section: Resultsmentioning

confidence: 76%

Interference of Heterophilic Antibody in D-dimer Determination in an Asymptomatic Elderly Woman

Sara,

Elena,

Mara

et al. 2024

IBRR

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Background: D-Dimer is considered a pivotal biomarker in diagnosis of disseminated intravascular coagulation and in differential diagnosis of thrombosis and pulmonary embolism. Case Summary: BL, Caucasian woman, 81 years old, was admitted to hospital, in October 2023, for concussive head trauma after an accidental fall. The patient had a "non-assayable D-Dimer due to excess antigen" utilizing Sysmex Innovance D-dimer using a Sysmex CS 5100 analyser. This abnormal result was firstly observed in March 2022. A second Laboratory confirmed the raised D-dimer concentration. The patient had undergone periodic D-dimer checks which had always confirmed the results and had been treated with a direct FXa inhibitor. Methods: Patient’s samples were tested for D-dimer using different assays and different analysers, moreover sample diluted in phosphate buffer and heterophilic antibodies blocking reagent have been tested. Results: The Sysmex Innovance D-dimer assay gave us, constantly “non-assayable D-dimer due to excess antigen" results; the HemosIL D-dimer HS assay gave us, constantly a raised D-dimer concentration (four to five higher than upper reference values); the Quidel Triage D-dimer gave us, constantly D-dimer normal concentration. Results obtained from dilution curves confirmed the presence of high concentration high avidity heterophilic antibodies. Conclusions: Reports regarding the influence of heterophilic antibodies on the measurement of D‐dimer are quite uncommon in literature however, they constitute a significant potential risk. Interference from heterophile antibodies often has a different impact using different instruments and methods in the measurement of D‐dimer. Using a combination of different assays and analysers, of dilution strategy with heterophilic antibody blockers, and combining laboratory results with clinical examinations and imaging data, we were able to identify the interference and exclude the presence of thrombosis.

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Section: Resultsmentioning

confidence: 76%

Interference of Heterophilic Antibody in D-dimer Determination in an Asymptomatic Elderly Woman

Sara,

Elena,

Mara

et al. 2024

IBRR

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“…15,17 In this study, we did not compare every specimen with a molecular weight-based method (e.g. GFC or sucrose gradient method 18 ) due to the impracticalities of testing a large number of samples. However, the Protein A method used in this study, including some specimens presented in this study, has been extensively compared to gel filtration chromatography.…”

Section: Discussionmentioning

confidence: 99%

Practical approaches to the detection of macrotroponin

Lam

Kyle

2023

Ann Clin Biochem

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Introduction: Macrotroponin is increasingly recognised as a cause of confusion in interpreting high-sensitivity cardiac troponin (hs-cTnI) results. In this study, we sought to evaluate two practical approaches to detecting macrotroponin. These two approaches are PEG precipitation and SVM (support vector machine) analysis to classify discrepancies between hs-cTn assays. Method: Residual serum and heparin plasma specimens (n=483) with initially elevated hs-cTnI from hospital and community laboratories were retested on multiple hs-cTn platforms before and after PEG precipitation and Protein A immunoglobulin depletion. SVM analysis was conducted to identify a linear equation that best discriminated specimens with macrotroponin using a combination of results from two different hs-cTn assays. Findings: The diagnostic performance of PEG precipitation was carried out using Protein A immunoglobulin depletion as the reference comparator. When a cutoff residual activity after PEG precipitation of ≤ 20% was used, this threshold carried a high specificity of 92% (confidence interval 83 – 98%; n = 189) using the Siemens hs-cTnI Vista assay and 95% specificity (86% - 98%; n = 242) using the Abbott hs-cTnI Architect assay. SVM analysis generated a linear equation identifying macrotroponin specimens from results obtained on two hs-cTn assays. This approach can be highly specific, comparable to PEG precipitation when certain assay combinations and concentrations are used. Conclusion: We describe and identify practical alternatives to detecting macrotroponin. These approaches can be optimised for high specificity, reducing the need for more complex laboratory methods.

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“…In healthy patients, interferences related to macrotroponin with cTn assays is possible and explained by the presence of anti‐troponin antibodies that interact with normal levels of circulating cTn (Figure 4A , Data S7 and Figure S4 ) which can lead to increased cTn results over several years. 44 , 65 Some cases of macrotroponin are also reported in the pediatric population. 66 , 67 In healthy patients, the level of hs‐cTn is generally slightly but significantly increased and stable on serial measurements, due to the slow clearance of the macrotroponin complexes.…”

Section: Troponin Antitroponin Antibodies and Macrotroponin In Routin...mentioning

confidence: 99%

“… 27 These interferences are unpredictable and generally unsuspected unless there is significant discrepancy between laboratory result and clinical assessment. 44 They can theoretically affect all types of cTn assays used in clinical practice, despite the use of blocking agents in the reagent formulation. 45 They are, however, often assay‐dependent, because the interference relies on the interaction with a given assay's antibodies.…”

Section: Endogenous Antibodies and Interferencesmentioning

confidence: 99%

Role of Antitroponin Antibodies and Macrotroponin in the Clinical Interpretation of Cardiac Troponin

Salaun,

Drory,

Coté

et al. 2024

JAHA

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Cardiac troponin is extensively used as a biomarker in modern medicine due to its diagnostic capability for myocardial injury, as well as its predictive and prognostic value for cardiac diseases. However, heterophile antibodies, antitroponin antibodies, and macrotroponin complexes can be observed both in seemingly healthy individuals and patients with cardiac diseases, potentially leading to false positive or disproportionate elevation of cTn (cardiac troponin) assay results and introducing discrepancies in clinical interpretations with impact on medical management. In this review article, we describe the possible mechanisms of cTn release and the sources of variations in the assessment of circulating cTn levels. We also explore the pathophysiological mechanisms underlying antitroponin antibody development and discuss the influence exerted by macrotroponin complexes on the results of immunoassays. Additionally, we explore approaches to detect these complexes by presenting various clinical scenarios encountered in routine clinical practice. Finally, unsolved questions about the development, prevalence, and clinical significance of cardiac autoantibodies are discussed.

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Methods for analyzing positive cardiac troponin assay interference

Cited by 9 publications

References 29 publications

Interference of Heterophilic Antibody in D-dimer Determination in an Asymptomatic Elderly Woman

Interference of Heterophilic Antibody in D-dimer Determination in an Asymptomatic Elderly Woman

Practical approaches to the detection of macrotroponin

Role of Antitroponin Antibodies and Macrotroponin in the Clinical Interpretation of Cardiac Troponin

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