Revisiting Diagnostic performances of serum erythropoïetin level and JAK2 mutation for polycythemias: analysis of a cohort of 1090 patients with red cell mass measurement

Abstract

We assessed the diagnostic performances of erythropoietin and JAK2 mutations in 1,090 patients with suspected polycythemia who were referred for red cell mass (RCM) measurement. In patients with a high haematocrit and/or haemoglobin level, a low erythropoietin level (<=3Á3 mUI/ml) and JAK2 mutation showed comparable positive predictive value (PPV) for true polycythemia (RCM>=125%), 92Á1% and 90% respectively. A very-low erythropoietin level (<=1Á99 mUI/ml) had a PPV of 100% for polycythemia vera (PV) diagnosis. We confirmed the correlations between RCM, erythropoietin and JAK2 variant allelic frequency in PV patients. This study prompts the need to revisit the role of EPO in PV diagnostic criteria.

Clinical features of acquired erythrocytosis: Low levels of serum erythropoietin in a subset of non‐neoplastic erythrocytosis patients

“…EPO was also significantly lower in the PV group ( p < 0.001, Figure 3H; Table S1), and all but two patients in the PV group exhibited EPO levels below the lower range of normal (<4.2 IU/L). Notably, 18 (40.8%) of the 44 NNE patients with available EPO data showed low EPO levels, which is a trait that has not been previously reported in NNE 15,16 …”

“…Notably, 18 (40.8%) of the 44 NNE patients with available EPO data showed low EPO levels, which is a trait that has not been previously reported in NNE. 15 , 16 …”

JAK2 V617F allele burden in polycythemia vera: burden of proof

“… 8 Further, higher JAK2 V617F VAF is associated with increased red cell mass, decreased serum iron, decreased transferrin saturation, and lower serum erythropoietin ( Table 1 ). 8 , 37 , 38 , 42 Excess HIF may be the basis of the reduced hepcidin, increased erythroferrone, and altered iron metabolism observed in patients with PV, although additional mechanisms may be at play. 43 PV neutrophils have increased HIF-mediated gene expression as well as increased expression of tissue factor, F3 , the primary initiator of the extrinsic pathway of coagulation, which again correlate with JAK2 V617F VAF ( Figure 1 B) 32 , 43 , 44 , 45 , 46 Further, clonal neutrophils in PV exhibited enhanced ability to release extracellular traps, activate integrin signaling, and enhance adhesion.…”