What is the treatment for erythrocytosis?

Treatment of Erythrocytosis

The treatment of erythrocytosis depends critically on distinguishing between primary (polycythemia vera) and secondary causes, with therapeutic phlebotomy to maintain hematocrit <45% and low-dose aspirin forming the cornerstone of management for polycythemia vera, while secondary erythrocytosis requires addressing the underlying cause with judicious use of phlebotomy only when hemoglobin exceeds 20 g/dL and hematocrit exceeds 65% with hyperviscosity symptoms. 1, 2

Initial Diagnostic Classification

Before initiating treatment, you must determine whether the erythrocytosis is primary or secondary:

• Measure serum erythropoietin (EPO) level as the key discriminator: low/normal EPO suggests primary erythrocytosis (polycythemia vera), while elevated EPO indicates secondary erythrocytosis 1, 3
• Screen for JAK2V617F mutation in all patients with suspected polycythemia vera, as nearly all PV patients harbor this mutation and its presence confirms the diagnosis 4, 5
• Evaluate for secondary causes including hypoxic conditions (COPD, sleep apnea, smoking, cyanotic heart disease), renal pathology (renal artery stenosis, renal cell carcinoma), EPO-secreting tumors, testosterone therapy, and SGLT2 inhibitor use 1, 6, 7

Management of Polycythemia Vera (Primary Erythrocytosis)

Risk Stratification

Classify patients into risk categories to guide intensity of therapy:

• High-risk: Age >60 years OR history of thrombosis 5
• Low-risk: Absence of both risk factors 5

Core Treatment Components

All patients with polycythemia vera require:

• Therapeutic phlebotomy to maintain hematocrit <45%, which significantly reduces cardiovascular death and major thrombotic events compared to targets of 45-50% 1, 5
• Low-dose aspirin (81-100 mg daily) reduces thrombotic complications by up to 60% in the absence of contraindications 1, 5

High-risk patients additionally require:

• Cytoreductive therapy with hydroxyurea as first-line agent 5
• Second-line options include interferon-α or busulfan for hydroxyurea failures 4, 5
• Ruxolitinib should be reserved only for severe protracted pruritus or marked splenomegaly unresponsive to other agents 5

Phlebotomy Protocol for Polycythemia Vera

• Remove one unit of blood (400-500 mL) per session 8
• Replace with equal volume of isotonic saline (750-1000 mL) 8
• Perform weekly or fortnightly until target hematocrit <45% is achieved 8
• Target serum ferritin of 50 μg/L during induction phase, but not lower to avoid iron deficiency 8

Management of Secondary Erythrocytosis

Primary Approach: Treat the Underlying Cause

The fundamental principle is addressing the root cause rather than routine phlebotomy:

• Treat sleep apnea with CPAP therapy 1
• Optimize management of COPD and chronic lung disease 1
• Consider dose reduction or formulation change for testosterone-induced erythrocytosis 1
• Adjust or discontinue causative medications when possible 1
• Smoking cessation counseling 6

Hydration as First-Line Symptomatic Therapy

• Ensure adequate hydration as first-line therapy for all patients with symptoms of hyperviscosity 1, 2
• Dehydration can exacerbate hyperviscosity symptoms and must be corrected before considering phlebotomy 1

Selective Use of Phlebotomy in Secondary Erythrocytosis

Phlebotomy is indicated ONLY when ALL of the following criteria are met:

• Hemoglobin >20 g/dL AND hematocrit >65% 8, 2
• Presence of hyperviscosity symptoms (headache, fatigue, poor concentration, visual disturbances) 8, 2
• Absence of dehydration or anemia 8

Special considerations for specific conditions:

• For hypoxic conditions (COPD, cyanotic heart disease): Judicious phlebotomy to hematocrit of 55-60% may improve exercise tolerance 1
• For cyanotic congenital heart disease: Maintain hematocrit around 60% and avoid aggressive phlebotomy to prevent iron deficiency and increased stroke risk 1, 8

Phlebotomy Protocol for Secondary Erythrocytosis

When criteria are met:

• Remove one unit of blood (400-500 mL) per session 8, 2
• Provide simultaneous equal volume replacement with isotonic saline or dextrose (750-1000 mL) 8, 2
• Frequency should be determined by symptom control rather than arbitrary hematocrit thresholds 3

Critical Pitfalls to Avoid

The Iron Deficiency Trap

Repeated routine phlebotomies are NOT recommended due to serious risks:

• Iron depletion paradoxically worsens symptoms by reducing oxygen-carrying capacity 8, 2
• Decreased red blood cell deformability increases blood viscosity despite lower hematocrit 1, 8
• Increased stroke risk in iron-deficient patients with erythrocytosis 1, 8

Inappropriate Phlebotomy

• Do not perform routine phlebotomy without meeting established criteria (Hgb >20 g/dL, Hct >65% with symptoms) 2
• Avoid phlebotomy in the presence of dehydration, as this represents relative erythrocytosis 8
• Do not overlook hydration status before considering phlebotomy 1

Monitoring Requirements

For All Patients with Erythrocytosis

• Regular complete blood counts to monitor hemoglobin and hematocrit 2
• Periodic iron status assessment (serum ferritin, transferrin saturation, peripheral blood smear) to avoid iron deficiency 8, 2
• Monitor for thrombotic events (both arterial and venous) 1, 2
• Assess for hyperviscosity symptoms before each intervention 8, 2

For Polycythemia Vera Specifically

• Monitor hematocrit regularly with goal <45% 1, 5
• Screen for acquired von Willebrand syndrome if platelet count >1,000 × 10⁹/L before administering aspirin 4
• Monitor for disease progression to myelofibrosis or acute leukemia 4, 5

Alternative Treatments for Special Circumstances

When standard phlebotomy is not feasible:

• Erythrocytapheresis allows removal of red cells while returning plasma and platelets, causing fewer hemodynamic changes 8, 2
• Iron chelation therapy (e.g., deferasirox) can be considered as second-line option after careful risk-benefit assessment 8, 2

Cardiovascular Risk Optimization

Although not supported by controlled trials, the following are commonly advised:

• Cardiovascular risk factor modification (hypertension, diabetes, hyperlipidemia management) 3
• Low-dose aspirin consideration for secondary erythrocytosis with cardiovascular risk factors, though evidence is limited outside of polycythemia vera 3