Diagnostic Considerations for Polycythemia Vera

Primary Diagnostic Criteria

The combination of elevated reticulocyte count, elevated RBC count, elevated hematocrit, and elevated MCHC most strongly suggests polycythemia vera (PV), particularly when iron deficiency has been corrected or is absent, as recommended by the European Society for Medical Oncology 1, 2
Polycythemia vera is the leading diagnosis when all three red cell parameters (RBC count, hematocrit, reticulocytes) are elevated together, especially with elevated or high-normal MCHC, according to the European Society for Medical Oncology 1, 2
The WHO diagnostic criteria for PV require hemoglobin >18.5 g/dL (men) or >16.5 g/dL (women), OR evidence of increased red cell volume, PLUS presence of JAK2V617F or JAK2 exon 12 mutation, as stated by the World Health Organization 1

Verify hydration status to exclude relative polycythemia, and repeat CBC after ensuring adequate hydration to confirm persistent elevation, as recommended by the American Society of Hematology 3, 4
Order JAK2V617F mutation testing (exon 14) as first-line, followed by JAK2 exon 12 mutation if negative, according to the National Comprehensive Cancer Network 1, 4
Positive JAK2 mutation with elevated hemoglobin/hematocrit fulfills major criteria for PV diagnosis, as stated by the European Society for Medical Oncology 1, 4

Phlebotomy is indicated only when hematocrit >65% with hyperviscosity symptoms in confirmed PV, and target hematocrit should be maintained strictly below 45% to reduce thrombotic risk, as recommended by the American College of Cardiology 2, 4
Low-dose aspirin is cornerstone therapy to prevent cardiovascular events, according to the European Society of Cardiology 2
Cytoreductive therapy (hydroxyurea or interferon-alpha) is recommended for high-risk patients (age >60 or prior thrombosis), as stated by the National Comprehensive Cancer Network 2