From the Guidelines
Yes, EPO levels can be normal in patients with Polycythemia Vera (PCV). This is supported by a study published in the Mayo Clinic Proceedings in 2003 1, which states that serum EPO levels may lie within the reference range in patients with a definite diagnosis of PV, with a sensitivity of a low serum EPO level for PV estimated to be less than 70%. The study highlights that a low serum EPO level is highly suggestive but not diagnostic of PV, and that PV remains a diagnostic consideration in the presence of either a low or normal serum EPO level.
Some key points to consider when evaluating EPO levels in PCV include:
- A low serum EPO level is not exclusive to PV and can also be found in other myeloproliferative disorders, such as essential thrombocythemia (ET) and congenital polycythemia with activating mutation of the EPOR.
- The presence of a normal or low serum EPO level in the setting of increased hemoglobin and hematocrit is considered paradoxical and helps clinicians make the diagnosis of PCV.
- Bone marrow examination with cytogenetic studies and other specialized tests may be necessary to confirm the diagnosis of PV in equivocal cases.
It is essential to note that the diagnosis of PCV is based on a combination of clinical, laboratory, and molecular features, and that EPO levels are just one aspect of the diagnostic work-up. As stated in the study 1, the demonstration of markedly decreased megakaryocyte expression of the TPO receptor (c-mpl) and the presence of a JAK2 mutation can support the diagnosis of PV.
From the Research
EPO Levels in PCV
- EPO levels are not always low in Polycythemia Vera (PV) patients, as previously thought 2
- There have been cases reported where PV patients had elevated EPO levels, with a mean Hb level of 20.2 gm/dl and an EPO level of 213 mlU/mL 2
- The presence of elevated EPO levels does not exclude a diagnosis of PV, and further testing for JAK2 mutation and bone marrow biopsy should be conducted if signs and symptoms suggest PV 2
Diagnosis and Treatment of PCV
- PV is a myeloproliferative neoplasm characterized by erythrocytosis and is almost universally associated with a JAK2 gene variant 3
- The goal of therapy for PV patients is to reduce thrombotic events by normalizing blood counts, and hydroxyurea (HU) and interferon-α (IFN-α) are commonly used cytoreductive options 4
- Therapeutic phlebotomy and low-dose aspirin are recommended for all PV patients, with cytoreductive therapy added for high-risk patients 3, 5
Treatment Outcomes
- HU and IFN-α have been shown to be effective in reducing thrombotic events and disease progression in PV patients, with IFN-α leading to a greater reduction in JAK2V617F at 24 months 4
- Phlebotomy and HU have been associated with improved overall survival and decreased risk of thrombosis in older PV patients, although these treatments are often underused in this population 5