What are the typical signs and symptoms of polycythemia vera in middle‑aged to older adults?

Symptoms of Polycythemia Vera

Polycythemia vera presents with a constellation of symptoms driven by hyperviscosity, thrombocytosis, and clonal myeloproliferation, most commonly affecting middle-aged to older adults (median age 60 years) with a slight male predominance. 1

Cardinal Clinical Manifestations

Hyperviscosity-Related Symptoms

• Headache, light-headedness, and transient neurologic disturbances occur due to impaired cerebral blood flow, particularly when hematocrit rises between 46-52% 2
• Transient visual changes affect approximately 14% of patients, resulting from microvascular occlusion in retinal vessels 3
• Tinnitus and atypical chest discomfort represent additional manifestations of hyperviscosity 1

Microvascular Disturbances

• Erythromelalgia presents in 3-5% of patients as painful burning sensations in the feet or hands with associated erythema and warmth 2, 3
• This distinctive symptom results from transient inflammation-based occlusive phenomena involving clonal platelet-endothelial interactions in arterioles 1
• Paresthesias commonly accompany other microvascular symptoms 1

Pruritus

• Aquagenic pruritus affects approximately 33% of patients, typically triggered by warm water exposure 3
• This symptom can be severe enough to significantly impair quality of life and may require specific cytoreductive therapy 1

Physical Examination Findings

• Splenomegaly is present in approximately 36% of patients at diagnosis and may cause abdominal discomfort 3
• Plethoric appearance with facial ruddiness reflects the elevated red cell mass 1

Hematologic Manifestations

• Erythrocytosis is the defining feature (hemoglobin >16.5 g/dL in men or >16.0 g/dL in women) 3
• Thrombocytosis occurs in 53% of patients at presentation 3
• Leukocytosis is present in 49% of cases 3

Thrombotic and Hemorrhagic Complications

Arterial Thrombosis

• Myocardial infarction and stroke represent the most common arterial complications, with 16% of patients experiencing arterial thrombosis prior to or at diagnosis 2, 3
• Suboptimal cerebral blood flow occurs specifically when hematocrit values reach 46-52% 2

Venous Thrombosis

• Splanchnic vein thrombosis (hepatic, portal, mesenteric veins) represents an unusual but characteristic presentation, occurring in 7% of patients at or before diagnosis 3
• These atypical site thromboses should prompt consideration of PV in the differential diagnosis 3

Bleeding Manifestations

• Acquired von Willebrand disease develops in more than one-third of PV patients, particularly with extreme thrombocytosis (platelet count ≥1000 × 10⁹/L) 2, 3
• Bleeding results from decreased large von Willebrand factor multimers due to abnormal adsorption to clonal platelets 2
• Poor platelet aggregation and decreased GP IIb/IIIa expression further contribute to hemorrhagic risk 2

Constitutional Symptoms

While the provided evidence focuses primarily on specific vascular and hematologic manifestations, constitutional symptoms such as fatigue, weight loss, and night sweats can occur but are less well-characterized in the available guidelines 1.

Important Clinical Caveats

Iron deficiency or bleeding can mask the underlying erythrocytosis by lowering red cell mass to within normal reference ranges, potentially delaying diagnosis 4. Serial measurements are more valuable than isolated readings for establishing the diagnosis 4.

The degree of leukocytosis does not consistently correlate with thrombosis risk, and leukocytosis lacks both sensitivity and specificity as a diagnostic criterion 4.

Untreated polycythemia vera historically resulted in median survival of less than 2 years, emphasizing the critical importance of recognizing and treating this condition 2. With modern therapy including phlebotomy and cytoreduction, median survival now ranges from 14.1 to 27.6 years 3.