Yoon Ji Sang, Kang Hyunhye, Jekarl Dong Wook, Lee Sung-Eun, Oh Eun-Jee
Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Research and Development Institute for In Vitro Diagnostic Medical Devices, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Diagnostics (Basel). 2024 Aug 29;14(17):1902. doi: 10.3390/diagnostics14171902.
Serum erythropoietin (sEPO) is an initial screening tool for distinguishing polycythemia vera (PV) from secondary erythrocytosis (SE), but defining 'subnormal' sEPO levels for PV diagnosis remains contentious, complicating its clinical utility. This study compares the diagnostic performance of sEPO across established subnormal limits, including reference interval (RI), clinical decision limit (CDL), and functional reference limit. sEPO levels were analyzed in 393 healthy donors (HDs) and 90 patients (41 PV and 49 SE), who underwent bone marrow biopsy and genetic tests due to erythrocytosis. The RI (2.5-97.5 percentile from HDs) of sEPO was 5.3-26.3 IU/L. A CDL of 3.1 IU/L, determined by ROC analysis in erythrocytosis patients, had a sensitivity of 80.5% and specificity of 87.8% for diagnosing PV. A functional reference limit of 7.0 IU/L, estimated based on the relationship between sEPO and hemoglobin, hematocrit, and WBC, increased sensitivity to 97.6% but decreased specificity to 46.7%. Using 5.3 IU/L as a 'subnormal' limit identified all three JAK2-negative PV cases, increasing the sensitivity and negative predictive value to 97.6% and 97.0%, respectively. Combining the RI, CDL, and functional reference limit may improve PV diagnostic accuracy.
血清促红细胞生成素（sEPO）是区分真性红细胞增多症（PV）和继发性红细胞增多症（SE）的初步筛查工具，但确定用于PV诊断的“低于正常”sEPO水平仍存在争议，这使其临床应用复杂化。本研究比较了sEPO在既定低于正常范围（包括参考区间（RI）、临床决策限（CDL）和功能参考限）下的诊断性能。对393名健康供体（HD）和90名患者（41例PV和49例SE）的sEPO水平进行了分析，这些患者因红细胞增多症接受了骨髓活检和基因检测。sEPO的RI（HD的第2.5 - 97.5百分位数）为5.3 - 26.3 IU/L。通过对红细胞增多症患者进行ROC分析确定的CDL为3.1 IU/L，对PV诊断的敏感性为80.5%，特异性为87.8%。基于sEPO与血红蛋白、血细胞比容和白细胞之间的关系估计的功能参考限为7.0 IU/L，敏感性提高到97.6%，但特异性降至46.7%。使用5.3 IU/L作为“低于正常”限可识别所有3例JAK2阴性PV病例，敏感性和阴性预测值分别提高到97.6%和97.0%。结合RI、CDL和功能参考限可能会提高PV诊断的准确性。
