J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://www.jocmr.org

Review

Volume 14, Number 2, February 2022, pages 80-87

False-Positive Causes in Serum Cardiac Troponin Levels

**Table 1.** Current Diagnostic Algorithms for Confirmation/Exclusion of NSTEMI Approved by the ESC: One-Hour NSTEMI Diagnostic Algorithm
Troponin immunoassay (company; manufacturer)	Biomarker concentration that indicates an extremely low probability of an NSTEMI diagnosis, ng/L	Biomarker concentration that indicates a low probability of an NSTEMI diagnosis, ng/L	Changes in biomarker concentration after 1 h at which a diagnosis of NSTEMI should be excluded, ng/L	Biomarker concentration that indicates a high probability of an NSTEMI diagnosis, ng/L	Changes in biomarker concentration after 1 h at which a diagnosis of NSTEMI should be confirmed, ng/L
High-sensitivity cardiac troponin T (Elecsys; Roche)	< 5	< 12	< 3	≥ 52	≥ 5
High-sensitivity cardiac troponin I (Architect; Abbott)	< 4	< 5	< 2	≥ 64	≥ 6
High-sensitivity cardiac troponin I (Centaur; Siemens)	< 3	< 6	< 3	≥ 120	≥ 12
High-sensitivity cardiac troponin I (Access; Beckman Coulter)	< 4	< 5	< 4	≥ 50	≥ 15
High-sensitivity cardiac troponin T (Clarity; Singulex)	< 1	< 2	< 1	≥ 30	≥ 6
High-sensitivity cardiac troponin T (Vitros; Clinical Diagnostics)	< 1	< 2	< 1	≥ 40	≥ 4
High-sensitivity cardiac troponin T (Pathfast; LSI Medience)	< 3	< 4	< 3	≥ 90	≥ 20

Table 1. Current Diagnostic Algorithms for Confirmation/Exclusion of NSTEMI Approved by the ESC: One-Hour NSTEMI Diagnostic Algorithm

Troponin immunoassay (company; manufacturer)

Biomarker concentration that indicates an extremely low probability of an NSTEMI diagnosis, ng/L

Biomarker concentration that indicates a low probability of an NSTEMI diagnosis, ng/L

Changes in biomarker concentration after 1 h at which a diagnosis of NSTEMI should be excluded, ng/L

Biomarker concentration that indicates a high probability of an NSTEMI diagnosis, ng/L

Changes in biomarker concentration after 1 h at which a diagnosis of NSTEMI should be confirmed, ng/L

High-sensitivity cardiac troponin T (Elecsys; Roche)

< 5

< 12

< 3

≥ 52

≥ 5

High-sensitivity cardiac troponin I (Architect; Abbott)

< 4

< 5

< 2

≥ 64

≥ 6

High-sensitivity cardiac troponin I (Centaur; Siemens)

< 3

< 6

< 3

≥ 120

≥ 12

High-sensitivity cardiac troponin I (Access; Beckman Coulter)

< 4

< 5

< 4

≥ 50

≥ 15

High-sensitivity cardiac troponin T (Clarity; Singulex)

< 1

< 2

< 1

≥ 30

≥ 6

High-sensitivity cardiac troponin T (Vitros; Clinical Diagnostics)

< 1

< 2

< 1

≥ 40

≥ 4

High-sensitivity cardiac troponin T (Pathfast; LSI Medience)

< 3

< 4

< 3

≥ 90

≥ 20

**Table 2.** Current Diagnostic Algorithms for Confirmation/Exclusion of NSTEMI Approved by the ESC: Two-Hour NSTEMI Diagnostic Algorithm
Troponin immunoassay (company; (manufacturer)	Biomarker concentration that indicates an extremely low probability of an NSTEMI diagnosis, ng/L	Biomarker concentration that indicates a low probability of an NSTEMI diagnosis, ng/L	Changes in biomarker concentration after 2 h at which a diagnosis of NSTEMI should be excluded, ng/L	Biomarker concentration that indicates a high probability of an NSTEMI diagnosis, ng/L	Changes in biomarker concentration after 2 h at which a diagnosis of NSTEMI should be confirmed, ng/L
High-sensitivity cardiac troponin T (Elecsys; Roche)	< 5	< 14	< 4	≥ 52	≥ 10
High-sensitivity cardiac troponin T (Architect; Abbott)	< 4	< 6	< 2	≥ 64	≥ 15
High-sensitivity cardiac troponin T (Centaur; Siemens)	< 3	< 8	< 7	≥ 120	≥ 20
High-sensitivity cardiac troponin T (Access; Beckman Coulter)	< 4	< 5	< 5	≥ 50	≥ 20
High-sensitivity cardiac troponin T (Clarity; Singulex)	< 1	To be determined	To be determined	≥ 30	To be determined
High-sensitivity cardiac troponin T (Vitros; Clinical Diagnostics)	< 1	To be determined	To be determined	≥ 40	To be determined
High-sensitivity cardiac troponin T (Pathfast; LSI Medience)	< 3	To be determined	To be determined	≥ 90	To be determined

Table 2. Current Diagnostic Algorithms for Confirmation/Exclusion of NSTEMI Approved by the ESC: Two-Hour NSTEMI Diagnostic Algorithm

Troponin immunoassay (company; (manufacturer)

Biomarker concentration that indicates an extremely low probability of an NSTEMI diagnosis, ng/L

Biomarker concentration that indicates a low probability of an NSTEMI diagnosis, ng/L

Changes in biomarker concentration after 2 h at which a diagnosis of NSTEMI should be excluded, ng/L

Biomarker concentration that indicates a high probability of an NSTEMI diagnosis, ng/L

Changes in biomarker concentration after 2 h at which a diagnosis of NSTEMI should be confirmed, ng/L

High-sensitivity cardiac troponin T (Elecsys; Roche)

< 5

< 14

< 4

≥ 52

≥ 10

High-sensitivity cardiac troponin T (Architect; Abbott)

< 4

< 6

< 2

≥ 64

≥ 15

High-sensitivity cardiac troponin T (Centaur; Siemens)

< 3

< 8

< 7

≥ 120

≥ 20

High-sensitivity cardiac troponin T (Access; Beckman Coulter)

< 4

< 5

≥ 50

≥ 20

High-sensitivity cardiac troponin T (Clarity; Singulex)

< 1

To be determined

≥ 30

To be determined

High-sensitivity cardiac troponin T (Vitros; Clinical Diagnostics)

< 1

To be determined

≥ 40

To be determined

High-sensitivity cardiac troponin T (Pathfast; LSI Medience)

< 3

To be determined

≥ 90

To be determined

**Table 3.** False-Positive Causes in Serum Cardiac Troponin Levels
Major factors	Reason of interference	References
Fibrin clots	Competitive interaction of fibrin clots with diagnostic antibodies	[17-19, 30, 31]
Heterophile antibodies	Cross interaction of heterophile antibodies with anti-cTn included in the diagnostic test system	[19, 20, 32-37]
Alkaline phosphatase	Endogenous alkaline phosphatase can catalyze the enzymatic reaction in immunoassay and thereby amplify the signal, which is proportional to the concentration of cardiac troponins in the sample	[3, 21, 22, 38, 39]
Rheumatoid factor	Nonspecific interaction of rheumatoid factor (autoantibodies) with diagnostic antibodies	[3, 27, 33, 40-45]
Cross-reactions of diagnostic (anti-cTn) antibodies with troponin molecules released from skeletal muscle	Cross-reactions of diagnostic antibodies with skeletal troponin molecules released into the bloodstream during skeletal muscle injury Re-expression of cardiac troponin molecules in skeletal muscles after injury and the release of these molecules into the bloodstream from skeletal muscle fibers	[47-49, 53]

Table 3. False-Positive Causes in Serum Cardiac Troponin Levels

Major factors

Reason of interference

References

Fibrin clots

Competitive interaction of fibrin clots with diagnostic antibodies

[17-19, 30, 31]

Heterophile antibodies

Cross interaction of heterophile antibodies with anti-cTn included in the diagnostic test system

[19, 20, 32-37]

Alkaline phosphatase

Endogenous alkaline phosphatase can catalyze the enzymatic reaction in immunoassay and thereby amplify the signal, which is proportional to the concentration of cardiac troponins in the sample

[3, 21, 22, 38, 39]

Rheumatoid factor

Nonspecific interaction of rheumatoid factor (autoantibodies) with diagnostic antibodies

[3, 27, 33, 40-45]

Cross-reactions of diagnostic (anti-cTn) antibodies with troponin molecules released from skeletal muscle

Cross-reactions of diagnostic antibodies with skeletal troponin molecules released into the bloodstream during skeletal muscle injury
Re-expression of cardiac troponin molecules in skeletal muscles after injury and the release of these molecules into the bloodstream from skeletal muscle fibers

[47-49, 53]