What are the symptoms and treatment options for Polycythemia?

Symptoms and Treatment of Polycythemia Vera

Polycythemia vera (PV) is characterized by erythrocytosis, thrombocytosis, and leukocytosis, with patients commonly experiencing symptoms including pruritus, erythromelalgia, transient visual changes, and splenomegaly with abdominal discomfort. 1

Common Symptoms

• Microvascular disturbances - including headache, light-headedness, transient neurologic or ocular disturbances, tinnitus, atypical chest discomfort, and paresthesias 2
• Erythromelalgia - painful and burning sensation of the feet or hands associated with erythema and warmth, occurring in approximately 3% of PV patients 2
• Pruritus - generalized itching often exacerbated by hot baths, documented in up to 48% of patients 2
• Splenomegaly - present in about 36% of patients, causing abdominal discomfort 1
• Thrombotic events - arterial thrombosis occurs in 16% and venous thrombosis in 7% of patients prior to or at diagnosis 1
• Bleeding - increased risk, especially in patients with extreme thrombocytosis (platelet count ≥1000 × 10^9/L) due to acquired von Willebrand disease 1

Diagnosis

• JAK2 mutation - present in >95% of PV cases, crucial for distinguishing from secondary causes of erythrocytosis 3, 1
• Erythrocytosis - hemoglobin >16.5 mg/dL in men or >16.0 mg/dL in women is a required diagnostic criterion 1
• Bone marrow morphology - remains the cornerstone of diagnosis 4

Risk Stratification

PV patients are stratified into risk categories to guide treatment decisions:

• High risk: Age ≥60 years or positive history of thrombosis 2, 3
• Low risk: Age <60 years and no history of thrombosis 2, 3

Treatment Options

First-line Treatment for All Patients

• Phlebotomy - maintain hematocrit <45% in all patients to reduce thrombotic risk 2, 3, 1
• Low-dose aspirin (81 mg daily) - for all patients without contraindications to prevent thrombotic complications 2, 3, 1

Cytoreductive Therapy for High-Risk Patients

• Hydroxyurea - first-line cytoreductive agent for high-risk patients (age >60 years or history of thrombosis) 2, 3
• Interferon-α - alternative first-line treatment, particularly recommended for:
  • Women of childbearing age due to potential teratogenicity of other agents 2, 3
  • Patients with intractable pruritus 2, 3
  • Young high-risk patients due to concerns about possible leukemogenicity with long-term hydroxyurea 3

Treatment for Specific Symptoms

• Pruritus - selective serotonin reuptake inhibitors have shown effectiveness 2
• Erythromelalgia - responds promptly to low-dose aspirin (81 mg/day) 2
• Severe symptoms or splenomegaly - ruxolitinib (JAK inhibitor) can be considered for patients intolerant or resistant to hydroxyurea 1, 4

Disease Complications and Prognosis

• Thrombotic events - major risk with 20-year rate of 26% 5
• Transformation to myelofibrosis - occurs in approximately 12.7% of patients 1
• Leukemic transformation - develops in about 6.8% of patients 1
• Median survival - ranges from 14.1 to 27.6 years from diagnosis 1

Treatment Pitfalls to Avoid

• Overzealous phlebotomy - can increase risk of stroke in certain conditions; maintain hematocrit at appropriate levels 2
• Ignoring extreme thrombocytosis - platelet counts ≥1000 × 10^9/L increase bleeding risk due to acquired von Willebrand disease 1
• Neglecting risk factors - failure to address modifiable vascular risk factors like smoking can worsen outcomes 2
• Inadequate hematocrit control - maintaining hematocrit strictly below 45% is essential to efficiently reduce thrombotic events 2

Current treatment strategies in PV have not been shown to prolong survival or reduce the risk of leukemic or fibrotic progression but are primarily directed at preventing thrombotic complications and managing symptoms 5, 4.