Development and validation of a simple correction method for the measurement of neuron-specific enolase in hemolyzed serum samples

The Neuron-specific enolase (NSE), a biomarker of neuroendocrine tumors or ischemic brain damage, has limited clinical applicability since its measurement is overestimated by hemolysis. In this study, an NSE correction method was developed for hemolyzed samples. The NSE concentration and the hemolysis index (HI) of serum were measured before and after spiking a hemolysate prepared with red blood cells from the serum-separating tube and extrapolating the NSE value corresponding to a HI of zero. To validate the approach (n = 46), NSE concentrations and HI were measured before (NSE0 and HI0) and after spiking the samples with 50 mu L (HIA, NSEA) and 100 mu L (HIB, NSEB) of hemolysate. A linear regression analysis was performed between (HIA, NSEA) and (HIB, NSEB). The y-intercept was taken as the corrected NSE concentration (NSEintercept) and compared with NSE0. On the same samples, the equation of Tolan et al. was applied and the corrected values of NSE (NSEcorr) were compared to NSE0. The average bias (+/- SD) between the NSE0 and the NSEintercept was equal to -3.2% (+/- 14.3) versus 34.6% (+/- 19.8) against the NSEcorr. Applying the allowable total error proposed by the European Federation of Laboratory Medicine, 72% of the NSE results were adequately corrected while the reference method corrected only 8.7% of the results. The individualized hemolysis correction method developed is simple, fast, requires one serum-separating tube, provides increased accuracy compared to the method described by Tolan et al. and should improve the quality of patient care.