What are the diagnostic criteria for Polycythemia Vera (PV)?

From the Guidelines

Diagnosing polycythemia vera requires meeting specific criteria established by the World Health Organization, including elevated hemoglobin or hematocrit levels and the presence of a JAK2 mutation, as outlined in the most recent and highest quality study 1.

Key Diagnostic Criteria

The diagnosis is made when a patient has:

• Elevated red cell mass, hemoglobin, or hematocrit levels
• Presence of a JAK2 mutation (V617F or other functionally similar mutations)
• Absence of secondary causes of erythrocytosis

Diagnostic Process

The diagnostic process typically begins with:

• A complete blood count showing elevated red blood cell parameters
• Genetic testing for JAK2 mutations
• Bone marrow examination to evaluate cellularity and rule out other myeloproliferative disorders
• Exclusion of secondary causes of polycythemia, such as chronic hypoxia, smoking, or kidney disease

Importance of Early Diagnosis

Early diagnosis is crucial as the condition increases the risk of thrombosis and can progress to myelofibrosis or acute leukemia if left untreated, as noted in 1 and 1.

Additional Considerations

It's essential to consider the presence of iron deficiency, which can confound the accurate interpretation of hemoglobin and hematocrit levels, as discussed in 1 and 1. In practice, meeting both of the newly proposed major criteria should capture more than 97% of cases with PV, as stated in 1. However, to minimize consequences of false-positive molecular test results and further optimize diagnostic specificity, the additional presence of at least one of the 3 minor criteria will be required to make a diagnosis of PV.

From the Research

Diagnosis of Polycythemia Vera

To make a diagnosis of polycythemia vera (PV), several factors need to be considered, including:

• Hemoglobin/hematocrit levels: A working diagnosis is considered in the presence of a JAK2 mutation associated with hemoglobin/hematocrit levels of >16.5 g/dL/49% in men or 16 g/dL/48% in women 2
• Morphologic confirmation: Bone marrow examination is advised but not mandated 2
• Red cell mass measurement: This is an important diagnostic criterion, and a red cell mass study should be performed in patients with suspected diagnosis of essential thrombocythemia or polycythemia vera and with hematocrit between 0.48 L/L and 0.52 L/L 3
• Bone marrow histomorphology: This is essential for diagnosis and baseline histomorphology, and can help distinguish PV from other JAK2V617F myeloproliferative neoplasms (MPNs) 4

Diagnostic Criteria

The diagnostic criteria for PV include:

• Major criteria: Elevated red blood cell mass, normal oxygen saturation, and palpable splenomegaly 5
• Minor criteria: Other features such as leukocytosis, thrombocytosis, and microcirculatory disturbances 2
• The 2016 World Health Organization (WHO) criteria: These criteria emphasize the importance of characteristic bone marrow findings and imply that hemoglobin/hematocrit threshold values may be used as surrogate markers for red cell mass measurements 6

Laboratory Tests

Laboratory tests that can aid in the diagnosis of PV include:

• Complete blood count (CBC): To evaluate hemoglobin, hematocrit, and red blood cell count
• Red cell mass measurement: To confirm the presence of an increased red blood cell mass
• Bone marrow biopsy: To evaluate bone marrow histomorphology and morphology
• JAK2 mutation testing: To detect the presence of a JAK2 mutation, which is commonly found in PV patients 2