Polycythemia Vera: Clinical Manifestations
Polycythemia vera presents most commonly with microvascular and neurologic symptoms, including headache, light-headedness, transient neurologic or visual disturbances, tinnitus, and atypical chest discomfort, which occur frequently in middle-aged to older adults with a median age at diagnosis of approximately 60 years. 1, 2
Epidemiologic Profile
- Median age at diagnosis is 60 years with a slight male predominance (1.2:1 ratio) 1, 2
- Approximately 7% of patients are diagnosed before age 40 years 1, 2
- Annual incidence is 0.5 to 4.0 cases per 100,000 persons 3
Microvascular and Neurologic Manifestations
These symptoms result from platelet-endothelial interactions causing transient thrombotic occlusion of arterioles 1:
- Headache and light-headedness are among the most common presenting complaints 1, 4
- Transient neurologic disturbances including visual changes (14% of patients) 1, 3
- Tinnitus (ringing in the ears) 1
- Atypical chest discomfort not typical of cardiac ischemia 1, 4
- Paresthesias (abnormal sensations) 1, 4
Dermatologic Manifestations
- Generalized pruritus occurs in 33-48% of patients, often dramatically exacerbated by hot baths or showers 1, 4, 3, 5
- Erythromelalgia affects approximately 3-5.3% of patients, presenting as painful burning sensations of the feet or hands with associated erythema and warmth 1, 2, 4, 3
Physical Examination Findings
- Splenomegaly is present in approximately 36% of patients at diagnosis, which may cause abdominal discomfort 2, 4, 3, 5
- Plethora (ruddy, flushed appearance) and engorged veins may be visible 1
Hematologic Abnormalities
- Erythrocytosis (hemoglobin >16.5 g/dL in men or >16.0 g/dL in women) is the defining feature 3, 5
- Thrombocytosis occurs in 53% of patients 3
- Leukocytosis occurs in 49% of patients 3
- Microcytosis from iron deficiency can develop, particularly in patients undergoing phlebotomy 1, 4
Constitutional Symptoms
- Fatigue, bone pain, and other non-specific constitutional symptoms are common and can significantly impact quality of life 4, 6
- These symptoms may warrant cytoreductive therapy even in lower-risk patients 4
Thrombotic and Hemorrhagic Complications
- Arterial thrombosis occurs in 16% of patients prior to or at diagnosis 3
- Venous thrombotic events occur in 7%, potentially involving unusual sites such as splanchnic veins (Budd-Chiari syndrome) 1, 3, 5
- Increased bleeding risk, especially with extreme thrombocytosis (platelet count ≥1000 × 10⁹/L) due to acquired von Willebrand disease 3
Diagnostic Molecular Marker
- JAK2 mutation is present in >95% of cases, which is essential for distinguishing PV from secondary causes of erythrocytosis such as tobacco smoking or sleep apnea 2, 4, 3, 5, 7
Long-term Disease Transformation Risk
- Transformation to myelofibrosis occurs in approximately 10-16% of patients within the first decade 1, 3, 5
- Transformation to acute myeloid leukemia occurs in approximately 5-7% of patients 1, 3, 5
- Median survival ranges from 14.1 to 27.6 years, with younger patients (≤40 years) having survival exceeding 35 years 3, 5