Ruiz Leyre, Munoz Tomás, González Alvaro, Alegre Estibaliz
Service of Biochemistry, Clínica Universidad de Navarra, Pamplona, Spain.
Science Faculty, Universidad de Navarra, Pamplona, Spain.
Biochem Med (Zagreb). 2025 Jun 15;35(2):020802. doi: 10.11613/BM.2025.020802.
Serum neuron specific enolase (NSE) is used as neuroendocrine tumor and central nervous system damage marker. It is present in variable concentrations in erythrocytes and hemolysis interferes in serum NSE quantification. Our aim was to develop a correction formula for moderate hemolysis, based on repeated patient samples instead of artificial sample doping with hemolysates.
We searched in laboratory informatics system for patients with sample pairs obtained within 24 h, for NSE quantification. We registered NSE and hemolytic index (NSE1 and HI1) from the first moderate hemolyzed sample (HI: 15-80), and from the second non-hemolyzed sample obtained afterwards (NSE2 and HI2). In a development cohort (N = 41), we obtained the formula NSE = NSE1 - (0.354 x (HI1 - HI2)) - 0.162, which was later used in the validation cohort (N = 26) to calculate NSE corrected concentrations (NSE).
Concentrations of NSE2 differed from NSE1 (P = < 0.001) but not from NSE (P = 0.291). In 84% samples, NSE1 had a relative bias from NSE that exceeded the 14% limit of total error allowable, with a median relative bias of 22.5%. Meanwhile, the bias between NSE2 concentrations and NSE was - 0.4 µg/L (95% confidence interval = - 3.8 to 4.5), the relative bias was 8.3% and only 23% of samples exceeded the 14% limit. Formula usefulness was limited to moderate hemolytic samples.
In summary, with this innovative approach, the NSE bias is low enough to have clinical significance, so re-drawings of blood samples might be avoided. This approach also opens the possibility to correct the estimation of other magnitude concentrations affected by hemolysis.
血清神经元特异性烯醇化酶（NSE）用作神经内分泌肿瘤和中枢神经系统损伤标志物。它在红细胞中浓度各异，溶血会干扰血清NSE定量。我们的目的是基于重复的患者样本而非用人为添加溶血产物的样本，开发一种针对中度溶血的校正公式。
我们在实验室信息系统中搜索24小时内获取的用于NSE定量的成对样本患者。我们记录了首个中度溶血样本（HI：15 - 80）的NSE和溶血指数（NSE1和HI1），以及之后获取的第二个非溶血样本的（NSE2和HI2）。在一个开发队列（N = 41）中，我们得到公式NSE = NSE1 - (0.354 x (HI1 - HI2)) - 0.162，该公式随后用于验证队列（N = 26）以计算NSE校正浓度（NSE）。
NSE2浓度与NSE1不同（P = < 0.001），但与NSE无差异（P = 0.291）。在84%的样本中，NSE1与NSE的相对偏差超过了允许的总误差14%的限度，中位相对偏差为22.5%。同时，NSE2浓度与NSE之间的偏差为 - 0.4 µg/L（95%置信区间 = - 3.8至4.5），相对偏差为8.3%，仅有23%的样本超过14%的限度。公式的实用性仅限于中度溶血样本。
总之，通过这种创新方法，NSE偏差低到具有临床意义，因此可能避免重新采集血样。这种方法也为校正受溶血影响的其他量级浓度的估计提供了可能性。
