Polycythemia Vera Represents Virtually All Cases of Primary Polycythemia
Polycythemia vera (PV) accounts for essentially 100% of primary (clonal) polycythemia cases, as it is the only recognized clonal myeloproliferative disorder that presents with isolated erythrocytosis as its defining feature. 1
Understanding the Classification Framework
The term "primary polycythemia" specifically refers to clonal (neoplastic) causes of erythrocytosis, which distinguishes it from secondary polycythemia (non-clonal, often EPO-mediated) and apparent polycythemia (spurious elevation due to plasma volume contraction). 1
Key Diagnostic Distinctions
PV is defined by clonal erythrocytosis that distinguishes it from other chronic myeloproliferative disorders like essential thrombocythemia (ET) and primary myelofibrosis (PMF), which do not present with erythrocytosis as their primary feature. 1
More than 95% of PV patients carry JAK2 mutations (JAK2V617F or exon 12 mutations), which are absent in secondary or spurious polycythemia, making this the molecular hallmark that confirms the clonal nature of the disease. 1, 2, 3
The JAK2V617F mutation frequency is 95% in PV compared to only 50% in ET and PMF, which primarily present with thrombocytosis and myelofibrosis respectively, not erythrocytosis. 1
Clinical Context
Why This Matters for Diagnosis
When evaluating a patient with true polycythemia (confirmed elevated red cell mass), the diagnostic algorithm focuses on distinguishing PV from secondary causes rather than identifying different types of primary polycythemia, because PV is the only primary form. 4
The differential diagnosis includes:
Secondary polycythemia causes: Hypoxia-driven conditions (chronic lung disease, high altitude, smoking), pathologic EPO production (renal cell cancer, hepatocellular carcinoma), congenital causes (high oxygen-affinity hemoglobinopathy), and drug-associated causes (EPO doping, androgen preparations). 4
Apparent polycythemia: Plasma volume contraction from dehydration, diuretics, or capillary leak syndrome. 1
Epidemiological Perspective
PV incidence is approximately 2.3 per 100,000 in population-based studies, making it more common than chronic myelogenous leukemia despite being considered rare. 1, 5
PV affects approximately 65,000 people in the US with an annual incidence of 0.5 to 4.0 cases per 100,000 persons. 2
Median age at diagnosis is approximately 60 years with a slight male preponderance (1.2:1), and only 7% of patients are diagnosed before age 40. 1
Common Diagnostic Pitfalls
Do not confuse the terminology: When clinicians ask about "what percentage of polycythemia is PV," they may be conflating all causes of elevated hemoglobin/hematocrit with primary polycythemia. In reality, secondary causes of polycythemia are collectively more common than PV. 5
The critical distinction is between primary (clonal) versus secondary (reactive) polycythemia, not between different subtypes of primary polycythemia, because PV is the sole entity in the primary category. 1