What is the management of erythrocytosis (excessive red blood cell production)?

Management of Erythrocytosis

Ensure adequate hydration first, identify and treat the underlying cause, and reserve therapeutic phlebotomy only for patients with hemoglobin >20 g/dL, hematocrit >65%, and symptomatic hyperviscosity—avoiding routine phlebotomies that risk iron depletion and paradoxically worsen outcomes. 1, 2

Initial Assessment and Diagnostic Approach

Determine if erythrocytosis is primary or secondary to guide management, as this fundamentally changes the treatment approach 1:

• Evaluate for hyperviscosity symptoms: headache, visual disturbances, fatigue, and poor concentration 1, 3
• Assess hydration status immediately, as dehydration causes relative erythrocytosis and must be corrected before any intervention 1, 3
• Check iron status through serum ferritin and transferrin saturation 3
• Identify secondary causes: hypoxemia, sleep apnea, cyanotic heart disease, smoking, SGLT-2 inhibitors, testosterone therapy, or other medications 1, 4

First-Line Management

Adequate hydration is the cornerstone of initial therapy for all patients with erythrocytosis 1:

• Hydration should be optimized before considering any invasive interventions 1
• Treat the underlying cause when secondary erythrocytosis is identified—this is the definitive management 1, 5
• For drug-induced erythrocytosis (testosterone, SGLT-2 inhibitors), discontinuation or dose adjustment often leads to improvement or resolution 4

Therapeutic Phlebotomy: Strict Criteria Required

Phlebotomy should NOT be performed routinely—it is reserved for specific high-risk situations 1, 2, 3:

Indications (ALL criteria must be met):

• Hemoglobin >20 g/dL AND hematocrit >65% 1, 2, 3
• Symptomatic hyperviscosity (headache, fatigue, poor concentration) 1, 2
• No evidence of dehydration or anemia 2

Phlebotomy Protocol:

• Remove 1 unit (400-500 mL) of blood per session 1, 2
• Replace with equal volume (750-1000 mL) of isotonic saline or dextrose simultaneously to maintain intravascular volume 1, 2
• For polycythemia vera specifically, target hematocrit <45% in men 2
• In cyanotic congenital heart disease, judicious phlebotomy to hematocrit ~60% may alleviate symptoms 2

Critical Pitfalls to Avoid

Routine or repeated phlebotomies are dangerous and contraindicated 1, 2, 3:

• Iron depletion from excessive phlebotomy paradoxically worsens outcomes by decreasing oxygen-carrying capacity, reducing red cell deformability, and increasing stroke risk 1, 2, 3
• Even in the presence of erythrocytosis, iron deficiency is undesirable and harmful 2
• Do not perform phlebotomy without meeting ALL established criteria (Hgb >20 g/dL, Hct >65%, symptoms, no dehydration) 1, 3

Alternative Treatments When Phlebotomy Not Feasible

• Erythrocytapheresis can be considered in selected cases, offering fewer hemodynamic changes and returning valuable blood components 1, 2
• Iron chelation therapy (e.g., deferasirox) is a second-line option after careful risk-benefit assessment 1, 2

Monitoring Strategy

Regular surveillance is essential to prevent complications 1, 3:

• Complete blood counts to track hemoglobin and hematocrit 1, 3
• Iron status monitoring (ferritin, transferrin saturation) to avoid iron deficiency, especially if any phlebotomy performed 1, 2, 3
• Assess for hyperviscosity symptoms at each visit 1, 3
• Monitor for thrombotic complications, as up to 20% of patients with cyanotic heart disease develop hemostatic abnormalities 1, 3
• Evaluate renal function, as chronic erythrocytosis can affect renal glomeruli 1

Special Populations

• Cyanotic congenital heart disease: Recognize that erythrocytosis is a physiological response to chronic hypoxemia to improve oxygen transport 1
• Pregnant women with mild-moderate iron overload: Phlebotomy can be paused during pregnancy in most cases 2
• Pre-operative patients: Occasional phlebotomy may be indicated to improve coagulation before elective surgery 2
• Elderly patients: Consider low-dose aspirin if secondary to myeloproliferative disorders and no contraindications exist 3