Can troponin (cardiac biomarker) give false positive results?

Troponin False Positive Results: Causes and Clinical Implications

Troponin elevations that do not reflect acute coronary syndromes are not true false positives but rather reflect non-ischemic myocardial injury, while true analytical false positives are rare and typically caused by immunoassay interferences. 1

Types of "False Positive" Troponin Results

True Analytical False Positives (Rare)

• Immunoassay interferences:
  • Heterophilic antibodies that interact with assay antibodies 1
  • Formation of macrotroponin (immunoglobulin-troponin complexes) 2
  • Biotin interference in biotin-streptavidin based assays 1
  • Endogenous antibodies against the troponin complex 1

Non-ACS Troponin Elevations (Not True False Positives)

These represent actual myocardial injury from non-coronary causes 1, 3:

1. Cardiac conditions:

   • Myocarditis
   • Heart failure
   • Takotsubo cardiomyopathy
   • Tachyarrhythmias/bradyarrhythmias
   • Valvular heart disease
   • Cardiac procedures/contusion/trauma

2. Systemic conditions:

   • Pulmonary embolism
   • Sepsis/critical illness
   • Renal dysfunction
   • Acute neurological events
   • Pulmonary hypertension
   • Extreme endurance exercise
   • Thyrotoxicosis

Clinical Approach to Elevated Troponin

Distinguishing True from False Elevations

1. Serial testing pattern:

   • Acute coronary syndromes typically show a rise and fall pattern
   • Stable elevations suggest chronic conditions or analytical interference 4
   • Reference change values (e.g., 46% increase or 32% decrease) help interpret serial results 4

2. Clinical correlation:

   • Evaluate symptoms, risk factors, and ECG findings
   • Consider pre-test probability of ACS versus other causes 3
   • Remember that troponin elevation is highly sensitive but less specific for ACS

3. Laboratory investigation of suspected analytical interference:

   • Consult with laboratory medicine when clinical picture doesn't match troponin results 2
   • Consider dilution studies, heterophile blocking tubes, or alternative assay methods 5

Important Clinical Considerations

1. High-sensitivity troponin assays:

   • Modern high-sensitivity assays can detect troponin in healthy individuals (threshold of detection: 0.006 ng/ml for hs-cTnI and 0.005 for hs-cTnT) 1
   • Positive results typically exceed the 99th percentile with a coefficient of variation <10% 1
   • Sex-specific 99th centile thresholds are recommended when using hs-cTn assays 1

2. Prognostic implications:

   • Troponin elevation predicts adverse outcomes regardless of cause 1, 3
   • Higher levels correlate with increased risk of death 1
   • Risk is independent of and additive to other risk factors 3

3. Pitfalls to avoid:

   • Assuming all troponin elevations indicate myocardial infarction 3
   • Failing to consider non-coronary causes of myocardial injury 3
   • Overlooking the possibility of analytical interference in clinically discordant cases 5
   • Ignoring the pattern of serial measurements 4

Conclusion

When evaluating troponin results, clinicians must consider both analytical factors and the broad spectrum of conditions that can cause myocardial injury. True analytical false positives are rare but important to recognize to avoid unnecessary interventions. Serial testing and careful clinical correlation are essential for accurate interpretation of troponin results.