Serum erythropoietin in the evaluation of erythrocytosis: How much does it contribute to the diagnosis of polycythemia vera?

INTRODUCTION: Serum erythropoietin (S. EPO) continues to be a minor diagnostic criterion for discriminating polycythemia vera (PV) from other causes of erythrocytosis. However, in the current era of Janus kinase 2 (JAK2) mutation testing, its relevance for establishing the diagnosis of PV is controversial. AIMS AND OBJECTIVES: The study aimed to assess the utility of S. EPO in patients with absolute erythrocytosis and ascertain its sensitivity and specificity for establishing the diagnosis of PV. Further, the clinicopathological features of PV and JAK2-EPOlow erythrocytosis were compared to discriminate the two disease states. MATERIALS AND METHODS: A total of 286 samples had undergone concomitant testing for S. EPO levels and JAK2V617F mutation for various indications over a period of 60 months (January 2017–December 2021). Clinical details and laboratory parameters were retrieved from the electronic medical records. RESULTS: Among 203/286 (70%) patients with erythrocytosis, JAK2 positivity was noted in 49 (24.1%) patients. A subnormal S. EPO level (<3.2 mIU/mL) was noted in only 27/43 (62.7%) cases of de novo PV, while the postphlebotomy PV patients (n = 6) had normal S. EPO levels. The sensitivity and specificity of low S. EPO for establishing the diagnosis of PV were 62.7% and 77.4%, respectively, while the sensitivity and specificity of high Hb levels (>16.5 g/dL) with low S. EPO and for diagnosing PV was 62.7% and 79.0%, respectively, while the sensitivity of high Hb levels with JAK2 positivity was 89.7%. In addition, 14.7% (30/203) of cases of high Hb/hematocrit (median: 18 g/dL and range: 16.3–23.8 g/dL) belonged to the JAK2-EPOlow subgroup. The median age of these patients, red blood cell count, total leukocyte count, and platelet count were, however, significantly lower as compared to the PV (P < 0.05). CONCLUSION: Overall, a low sensitivity and specificity of S. EPO were observed for diagnosing PV as an isolated investigation, thus questioning its diagnostic utility, though high levels had an excellent negative predictive value. However, this simple and inexpensive test remains an important screening tool for evaluating patients with absolute erythrocytosis.