What is the management approach for a patient with chronic erythrocytosis (elevated red blood cell count) lasting over a year?

Management of Chronic Erythrocytosis (Elevated Red Blood Cell Count for Over One Year)

For a patient with chronic erythrocytosis lasting over a year, the first priority is to distinguish between polycythemia vera (PV) and secondary erythrocytosis by testing for JAK2 mutation and measuring serum erythropoietin (EPO) levels, as this fundamentally determines all subsequent management decisions. 1, 2

Diagnostic Algorithm

Step 1: Confirm True Erythrocytosis

• Ensure adequate hydration status before proceeding, as relative erythrocytosis from dehydration is common and must be excluded first 3
• Verify hemoglobin >16.5 g/dL in men or >16.0 g/dL in women, with corresponding hematocrit >49% in men or >48% in women 2, 4

Step 2: Order JAK2 Mutation Testing and Serum EPO Level

• JAK2 mutation (V617F or exon 12) testing is the single most important initial test - over 95% of PV patients are JAK2-positive 1, 2
• Measure serum EPO level simultaneously: subnormal EPO suggests PV, while normal or elevated EPO indicates secondary erythrocytosis 1, 4
• This two-test approach immediately separates clonal (PV) from non-clonal (secondary) erythrocytosis 1

Step 3: Additional Workup Based on Initial Results

If JAK2-positive with low EPO (likely PV):

• Bone marrow biopsy is advised for morphologic confirmation, though not absolutely mandated if JAK2 mutation is present 5
• Assess for splenomegaly (present in 36% of PV patients) 2
• Screen for symptoms: pruritus (33%), erythromelalgia (5.3%), visual changes (14%) 2

If JAK2-negative with normal/elevated EPO (secondary erythrocytosis):

• Evaluate for hypoxemia: assess cardiopulmonary symptoms, consider sleep apnea screening, smoking history 3, 4
• Check iron status with serum ferritin and transferrin saturation 3
• Perform peripheral blood smear to evaluate red cell morphology 3

Risk Stratification for Polycythemia Vera

High-risk patients (require cytoreductive therapy in addition to phlebotomy):

• Age ≥60 years OR prior thrombosis history 6, 2, 5

Low-risk patients (phlebotomy and aspirin alone):

• Age <60 years AND no thrombosis history 6, 5

Treatment Approach

For All Patients with Polycythemia Vera (Regardless of Risk)

Therapeutic phlebotomy is mandatory:

• Target hematocrit <45% in all patients 6, 2, 5
• Remove one unit (400-500 mL) per session, replacing with equal volume of isotonic saline (750-1000 mL) 7
• Perform weekly or fortnightly until target reached, then adjust frequency based on individual red cell production rate 7

Low-dose aspirin (81-100 mg daily):

• Administer to all patients unless contraindications exist (such as extreme thrombocytosis ≥1000 × 10⁹/L with acquired von Willebrand disease) 6, 2, 5

For High-Risk Polycythemia Vera Patients

Add cytoreductive therapy:

• First-line options: Hydroxyurea OR pegylated interferon-α 6, 5
• Interferon is preferred for younger patients or pregnant patients requiring cytoreduction 6
• Second-line options: Busulfan or ruxolitinib (for hydroxyurea-resistant/intolerant patients, especially with persistent pruritus or splenomegaly) 2, 5

Indications for cytoreductive therapy include: 6

• Frequent/persistent need for phlebotomy with poor tolerance
• Symptomatic or progressive splenomegaly
• Symptomatic thrombocytosis
• Progressive leukocytosis
• Progressive disease-related symptoms (pruritus, night sweats, fatigue)

For Secondary Erythrocytosis

Treat the underlying cause: 3, 4

• Address hypoxemia (supplemental oxygen if indicated)
• Treat sleep apnea with CPAP
• Smoking cessation counseling
• Manage chronic lung disease

Phlebotomy is NOT routinely recommended for secondary erythrocytosis unless: 3, 7

• Hemoglobin >20 g/dL AND hematocrit >65% with symptoms of hyperviscosity (headache, visual disturbances, fatigue, poor concentration)
• Congenital heart disease with cyanosis causing symptoms (target hematocrit ~60%) 7

Hydration is first-line therapy for all secondary erythrocytosis patients 3

Critical Pitfalls to Avoid

Iron Deficiency Management

• Iron deficiency can mask the full extent of erythrocytosis while paradoxically increasing stroke risk 3, 7
• Monitor iron status with ferritin and transferrin saturation regularly 3
• Cautious iron supplementation with close hemoglobin monitoring is appropriate when iron deficiency is documented 3
• Target serum ferritin of 50 μg/L during phlebotomy induction phase, but not lower 7

Phlebotomy Cautions

• Avoid routine repeated phlebotomies in secondary erythrocytosis - they cause iron depletion, decreased oxygen-carrying capacity, and increased stroke risk 3, 7
• Never perform phlebotomy in the presence of dehydration or anemia 7
• Bone marrow biopsy should be performed before initiating cytoreductive therapy to rule out progression to myelofibrosis 6

Monitoring Strategy

For patients on phlebotomy therapy:

• Monitor hemoglobin and hematocrit before each session 7
• Assess for hyperviscosity symptoms (headache, fatigue, poor concentration) 3, 7
• Check iron status periodically to detect iron deficiency early 3, 7

For PV patients on cytoreductive therapy:

• Monitor response every 3-6 months or more frequently as clinically indicated 6
• Assess for new thrombosis or bleeding 6
• Manage cardiovascular risk factors aggressively 6
• Monitor for disease progression to myelofibrosis (16% at 20 years) or acute myeloid leukemia (4% at 20 years) 5

For secondary erythrocytosis patients:

• Monitor hemoglobin and hematocrit periodically 3
• Reassess underlying cause and optimize treatment 3, 4