Low neutrophil-to-lymphocyte ratio identifies secondary polycythemia in patients with erythrocytosis

The neutrophil-to-lymphocyte ratio (NLR), a simple marker of systemic inflammation, may assist in differentiating polycythemia vera (PV) from secondary polycythemia (SP), especially when access to JAK2 mutation testing is limited due to cost or delayed turnaround. We retrospectively analyzed 655 patients with erythrocytosis who underwent JAK2 mutation testing between 2007 and 2024 across three South Korean tertiary hospitals. PV and SP were diagnosed per 2016 WHO criteria. NLR was calculated from complete blood counts and compared to serum erythropoietin (EPO) using receiver operating characteristic (ROC) analysis. The mean NLR was significantly higher in PV than SP (6.92 vs. 2.24, p < 0.001). NLR outperformed EPO in distinguishing PV (AUC 0.919 vs. 0.835, p < 0.001), and the combination further improved diagnostic accuracy (AUC 0.955). Notably, 98.8% (159/161) of patients with NLR < 1.5 had SP, suggesting these patients may safely undergo delayed JAK2 testing while secondary causes are prioritized. NLR may serve as a cost-effective triage marker to identify patients at low risk for PV, potentially reducing unnecessary molecular testing and expediting appropriate diagnostic pathways in erythrocytosis.