title: Individualized correction of neuron-specific enolase (NSE) measurement in hemolyzed serum samples.
abstract: BACKGROUND
  Accuracy of serum neuron-specific enolase (NSE) measurement is paramount, particularly in the context of neurological outcome prognostication. However, NSE measurements are compromised by even slight hemolysis, as it is abundant in red blood cells (RBCs). We derived and validated an individualized hemolysis correction equation in an attempt to reduce the current rejection rate of 14% at our institution.
  
  
  METHODS
  Intracellular NSE was measured in RBC lysates to determine concentration variability. A correction equation was derived, accounting for both RBC-derived NSE false-elevation and hemoglobin-derived signal quenching. The performance of this individualized correction was evaluated in intentionally hemolyzed samples and accuracy was compared to a generalized correction.
  
  
  RESULTS
  Significant inter-individual variability of RBC NSE was observed, with an almost two-fold range (15.7-28.5 ng NSE/mg Hb, p<0.001); intra-individual variability was insignificant. The individualized hemolysis correction equation derived: NSE(corr)=NSE(meas)-(Hb(serum))(NSE(RBCs/Hb))+0.0844(Hb(serum))+1.1 corrected 95% of the intentionally hemolyzed samples to within ±5 ng/ml of corresponding baseline NSE concentrations, compared to 74% using a generalized formula.
  
  
  CONCLUSIONS
  The individualized hemolysis correction provides increased accuracy in the estimation of true serum NSE concentrations for hemolyzed samples, compared to a generalized approach, by accounting for inter-individual RBC NSE variability. Incorporating this correction should reduce sample rejection rates and overall health care costs.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States.
authors.forename: Nicole V
authors.initials: NV
authors.lastname: Tolan
authors.forename: Noemi
authors.initials: N
authors.lastname: Vidal-Folch
authors.forename: Alicia
authors.initials: A
authors.lastname: Algeciras-Schimnich
authors.forename: Ravinder J
authors.initials: RJ
authors.lastname: Singh
authors.forename: Stefan K G
authors.initials: SK
authors.lastname: Grebe
mesh_terms: D004912:Erythrocytes / Q000737:chemistry* / Q000201:enzymology; D006454:Hemoglobins / Q000737:chemistry; D006461:Hemolysis; D006801:Humans; D007527:Isoenzymes / Q000097:blood; D010751:Phosphopyruvate Hydratase / Q000097:blood*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D006454:Hemoglobins; D007527:Isoenzymes; D010751:Phosphopyruvate Hydratase
keywords: Individualized hemolysis correction; Ischemic brain injury; Neurological prognosis; Neuron-specific enolase; Therapeutic hypothermia