Serum Erythropoietin Measured by Chemiluminescent Immunometric Assay: An Accurate Diagnostic Test for Absolute Erythrocytosis

Abstract

Absolute erythrocytosis (AE), suspected from a high hemoglobin concentration and/or hematocrit, can be confirmed by an increased red cell mass (RCM) (1). Schematically, one distinguishes three major mechanisms of AE: (a) erythropoietin (Epo)-independent proliferation of clonal erythroid precursors as found in polycythemia vera (PV) and other myeloproliferative disorders; (b) Epo-dependent polyclonal proliferation of erythroid precursors as found in secondary erythrocytoses that are secondary to production of Epo as a consequence of either a physiologic response to tissue hypoxia or of tumoral production; (c) idiopathic erythrocytoses (IEs) in patients without evidence of PV or secondary erythrocytoses (2). The serum Epo concentration reflects its oxygen-regulated production by kidney. Thus, serum Epo is decreased in PV and increased in secondary erythrocytoses. Use of serum Epo as a diagnostic test for PV (3)(4)(5) is controversial(6)(7)(8). Indeed, until recently, the lack of standardization of the reagents and methods impeded identification of reliable thresholds. As a consequence, the diagnosis of PV is still largely based on exclusion and/or indirect clinical and biological criteria initially proposed by the Polycythemia Vera Study Group (PVSG) (9). However, the WHO guidelines (10), which are based on major criteria (e.g., splenomegaly, lack of secondary erythrocytosis) and minor criteria (e.g., modification in blood cell count, bone marrow histology), recently classified the endogenous erythroid colony assay and serum Epo measurements as major and minor PV diagnostic criteria, respectively. We recently demonstrated in a large multicenter study (n = 241) that a commercial ELISA for serum Epo was a reliable and accurate biological diagnostic test in patients with AE (11). In this study, we determined a low Epo threshold with 65% sensitivity and 100% specificity for the diagnosis of PV and a high Epo threshold with 19.7% sensitivity and 100% specificity for secondary erythrocytoses. …