What are the symptoms and treatment options for Polycythemia Vera (PV)?

Polycythemia Vera Symptoms

Polycythemia vera presents with a characteristic triad of microvascular disturbances, pruritus, and splenomegaly, along with an elevated thrombotic risk that defines its clinical course. 1

Cardinal Symptoms

Microvascular Disturbances

• Headache, light-headedness, transient neurologic or ocular disturbances, tinnitus, atypical chest discomfort, and paresthesias are common manifestations resulting from platelet-endothelial interactions in arterioles 2, 1
• These symptoms reflect transient inflammation-based occlusive phenomena caused by clonal platelet dysfunction 2

Erythromelalgia

• Painful burning sensation of the feet or hands with associated erythema and warmth occurs in approximately 3% of PV patients 2, 1
• This syndrome is often associated with thrombocythemia and involves platelet-mediated endothelial injury 2
• Low-dose aspirin (81 mg/day) produces prompt relief within hours in most patients with PV-associated erythromelalgia 2, 1
• Patients who don't respond to aspirin may require cytoreductive therapy to normalize platelet counts 2

Pruritus

• Generalized itching, often exacerbated by hot baths, affects up to 48% of patients either at diagnosis or during disease course 2, 1
• This can be the most debilitating symptom, causing sleep deprivation and interference with daily activities 2
• Selective serotonin reuptake inhibitors (like paroxetine) show response rates exceeding 80% for PV-associated pruritus 2, 1
• Antihistamines produce unpredictable and variable responses 2
• Some evidence suggests correlation with iron deficiency (low mean corpuscular volume), and iron replacement may benefit select patients 2

Splenomegaly

• Splenomegaly with abdominal discomfort occurs in approximately 36% of patients 3
• Painful splenomegaly with infarction or compression of surrounding viscera represents an accepted indication for splenectomy 4

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 3
• Leukocytosis is present in 49% of patients 3

Visual Symptoms

• Transient visual changes affect approximately 14% of patients 3
• These represent microvascular occlusive phenomena affecting ocular circulation 2

Thrombotic and Hemorrhagic Complications

Thrombosis Risk

• Prior to or at diagnosis, arterial thrombosis occurs in 16% and venous thrombosis in 7% of patients 3
• Venous thrombosis can involve unusual sites, particularly splanchnic veins 3, 5
• The 20-year thrombotic event rate reaches 26% 5

Bleeding Risk

• Increased bleeding risk occurs, especially with extreme thrombocytosis (platelet count ≥1000 × 10⁹/L) due to acquired von Willebrand disease 3

Disease Transformation

Long-term Complications

• Approximately 12.7% of patients develop myelofibrosis 3
• Acute myeloid leukemia develops in 6.8% of patients 3
• In the first decade, transformation rates are estimated at 10% for myelofibrosis and 5% for leukemia, with progressive increase beyond the first decade 2

Diagnostic Considerations

JAK2 Mutation

• More than 95% of PV patients harbor the JAK2V617F mutation, which is crucial for distinguishing PV from secondary erythrocytosis causes like smoking or sleep apnea 1, 6, 3

Common Pitfalls

• Failure to recognize microvascular symptoms as PV-related can delay appropriate aspirin therapy 2
• Undertreating pruritus with conventional antihistamines alone when SSRIs show superior efficacy 2, 1
• Missing the diagnosis in patients presenting with thrombosis in unusual sites (splanchnic veins) without recognizing underlying PV 3, 5
• Not screening for acquired von Willebrand disease in patients with extreme thrombocytosis before procedures 3