What are the symptoms and management of polycythemia in a patient with suspected polycythemia vera?

Symptoms of Polycythemia Vera

Polycythemia vera presents with a characteristic constellation of symptoms including microvascular disturbances (headache, light-headedness, transient neurologic or ocular disturbances, tinnitus, atypical chest discomfort, paresthesias), generalized pruritus (occurring in 33-48% of patients), and erythromelalgia (painful burning sensation of hands/feet with erythema and warmth in approximately 3-5.3% of patients). 1, 2, 3

Neurological and Microvascular Symptoms

The hyperviscosity from elevated red blood cell mass causes a range of neurological manifestations:

• Headache and light-headedness are among the most common presenting symptoms 1, 4
• Transient neurologic or ocular disturbances occur frequently, including visual changes (reported in 14% of patients) 1, 3
• Tinnitus (ringing in the ears) results from microvascular compromise 1
• Atypical chest discomfort may mimic cardiac symptoms 1, 4
• Paresthesias (numbness/tingling sensations) affect the extremities 1, 4

Erythromelalgia

This is a highly characteristic but relatively uncommon manifestation:

• Occurs in approximately 3-5.3% of PV patients, making it a specific but not sensitive finding 1, 2, 3
• Presents as painful, burning sensation of the feet or hands associated with erythema and warmth 1, 2
• Often associated with thrombocythemia, with pathogenesis involving platelet-mediated endothelial cell injury and transient thrombotic occlusion by platelet aggregates 1
• Responds promptly (within hours) to low-dose aspirin (81 mg/day) in most patients, though some require cytoreductive therapy to normalize platelet counts 1, 4

Pruritus (Itching)

This is one of the most debilitating symptoms:

• Documented in 33-48% of patients, making it one of the most common symptoms 1, 2, 3
• Characteristically exacerbated by hot baths (aquagenic pruritus), which is highly suggestive of PV when present 1
• May be the most agonizing aspect of PV, resulting in sleep deprivation and interference with social and physical activities 1
• Treatment options include:
  • Paroxetine (selective serotonin reuptake inhibitor) with >80% response rate 1, 2
  • Interferon-α, which reduces pruritus in up to 81% of affected patients and is recommended for intractable cases 1, 2
  • Aspirin therapy may provide benefit through inhibition of platelet release of pruritogenic amines 1
  • Ruxolitinib produces rapid reductions in pruritus scores 1

Important caveat: Iron replacement therapy has not been consistently effective for PV-associated pruritus despite some correlation with iron deficiency, and its indiscriminate use is discouraged 1

Physical Examination Findings

• Splenomegaly is present in approximately 36% of patients and may cause abdominal discomfort 2, 3
• Plethoric (ruddy) appearance of the face and extremities from increased red blood cell mass 1

Hematologic Abnormalities

• Erythrocytosis is required for diagnosis (hemoglobin >16.5 g/dL in men or >16.0 g/dL in women) 3, 5
• Thrombocytosis occurs in 53% of patients 3
• Leukocytosis occurs in 49% of patients 3
• Microcytosis from iron deficiency can occur, particularly in patients undergoing phlebotomy 1, 2

Constitutional Symptoms

• Fatigue is the most frequently reported symptom and can persist despite blood count control 6
• Non-specific constitutional symptoms including weight loss, fevers, and night sweats may occur 1, 2
• These symptoms significantly impact quality of life and may warrant cytoreductive therapy even in lower-risk patients 2

Thrombotic and Hemorrhagic Complications

• Arterial thrombosis occurs in 16% of patients prior to or at diagnosis 3
• Venous thrombotic events occur in 7%, which can involve unusual sites such as splanchnic veins (Budd-Chiari syndrome) 1, 3
• Increased bleeding risk, especially with extreme thrombocytosis (platelet count ≥1000 × 10⁹/L) due to acquired von Willebrand disease 3

Diagnostic Clue

The JAK2 mutation is present in >95% of PV cases and is crucial for distinguishing it from secondary causes of erythrocytosis such as tobacco smoking, sleep apnea, or chronic lung disease 1, 2, 4, 3

Critical pitfall to avoid: Symptoms can persist despite achieving complete hematologic remission or controlled blood counts, indicating some discordance between laboratory values and symptom burden 6. Therefore, regular monitoring of symptom burden should be factored into the assessment of disease control, not just blood count targets 6.