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Managing hemolysis in serum neuron-specific enolase measurements - an automated algorithm for routine practice
Ragnhild V Nome1, Elisabeth Paus1, Johanna E Gehin1
1Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
Summary
Hemolysis falsely elevates Neuron-specific enolase (NSE) levels. A new algorithm corrects NSE results based on hemolysis degree, improving biomarker reliability for neuroendocrine tumors and cardiac arrest prognostication.
Area of Science:
- Biochemistry
- Clinical Chemistry
- Medical Diagnostics
Background:
- Neuron-specific enolase (NSE) is a biomarker for neuroendocrine tumors and prognostication in cardiac arrest survivors.
- Hemolysis, the rupture of red blood cells, leads to falsely elevated NSE levels due to NSE presence in erythrocytes and platelets.
Purpose of the Study:
- To develop and validate an algorithm for correcting NSE levels affected by hemolysis.
- To assess the uncertainty associated with corrected NSE (cNSE) results.
Main Methods:
- Serial dilutions of native serum and hemolysate from 30 patients were used to measure NSE (mNSE) and hemolytic index (HI).
- An algorithm was developed correlating mNSE, HI, and hemolytic interference.
- An equation for cNSE was derived for samples with limited hemolysis (5 < HI ≤ 30): cNSE = mNSE - HI × (0.34 ± 0.23) µg/L.
Main Results:
- A validated algorithm was created to correct NSE levels based on the degree of hemolysis.
- The algorithm provides a corrected NSE (cNSE) value and estimates uncertainty.
- A formula was established for limited hemolysis: cNSE = mNSE - HI × (0.34 ± 0.23) µg/L.
Conclusions:
- An automated algorithm can effectively manage hemolysis interference in serum NSE measurements.
- The developed algorithm improves the reliability of NSE as a biomarker.
- Clinicians and laboratorians must remain aware of potential limitations, especially with in vivo hemolysis.

