What is the treatment for erythrocytosis (excessive red blood cell production)?

Treatment of Erythrocytosis

Therapeutic phlebotomy should only be performed when hemoglobin exceeds 20 g/dL and hematocrit exceeds 65% with documented hyperviscosity symptoms (headache, fatigue, visual disturbances, poor concentration) in the absence of dehydration or anemia. 1, 2

Initial Management Priorities

Hydration and Underlying Cause Identification

• Ensure adequate hydration as first-line therapy for all patients with erythrocytosis, as dehydration can falsely elevate hematocrit and worsen hyperviscosity 2
• Identify and treat the underlying cause of secondary erythrocytosis (hypoxemia, sleep apnea, cyanotic heart disease, renal artery stenosis, EPO-secreting tumors, androgen therapy, SGLT-2 inhibitors) before considering phlebotomy 1, 2
• Measure arterial oxygen saturation, carboxyhemoglobin levels (especially in smokers), and serum EPO levels to distinguish primary from secondary causes 1

Critical Principle: Avoid Routine Phlebotomy

• Repeated routine phlebotomies are contraindicated due to the risk of iron depletion, decreased oxygen-carrying capacity, and increased stroke risk 1, 2
• Most patients with erythrocytosis have compensated erythrocytosis with stable hemoglobin requiring no intervention 1
• The increased red blood cell mass is often a physiological compensatory response to improve oxygen transport, not a pathological process requiring treatment 1, 2

Therapeutic Phlebotomy Protocol (When Indicated)

Strict Indications

Perform phlebotomy only when all three criteria are met:

• Hemoglobin >20 g/dL AND
• Hematocrit >65% AND
• Documented hyperviscosity symptoms (headache, fatigue, visual changes, poor concentration) with no evidence of dehydration 1, 2, 3

Phlebotomy Technique

• Remove 1 unit (400-500 mL) of blood per session 1, 3
• Simultaneously replace with equal volume (400-500 mL) of isotonic saline or dextrose solution to prevent hemodynamic instability 1, 2
• In elderly patients or those with cardiovascular disease, consider smaller volumes (250-300 mL) to minimize hemodynamic stress 3

Target Hematocrit Levels by Condition

• Cyanotic congenital heart disease: Target hematocrit ~60% with judicious phlebotomy to alleviate hyperviscosity symptoms while maintaining oxygen delivery 1
• Chronic obstructive pulmonary disease (COPD): Target hematocrit 55-60% to improve exercise tolerance and cardiac function 1
• Polycythemia vera: Maintain hematocrit strictly <45% regardless of sex through regular phlebotomy plus aspirin 4, 3

Mandatory Monitoring to Prevent Complications

Iron Status Surveillance

• Monitor iron status with every phlebotomy session using peripheral blood smear and serum ferritin or transferrin saturation 1, 2, 3
• Iron deficiency, even in the presence of erythrocytosis, is dangerous because it reduces oxygen-carrying capacity, decreases red cell deformability (microcytosis), and increases stroke risk 1, 2
• If iron deficiency develops, oral iron supplementation should be given cautiously with close hemoglobin monitoring, as rapid increases in red cell mass can occur 1
• In patients intolerant of oral iron, use pulses of intravenous iron supplementation 1

Hemoglobin Monitoring

• Check hemoglobin before each phlebotomy session 1
• If hemoglobin drops below 12 g/dL, reduce phlebotomy frequency 1
• If hemoglobin drops below 11 g/dL, pause phlebotomy treatment 1

Pharmacological Alternatives

ACE Inhibitors and Angiotensin II Receptor Blockers

• Effective in lowering hematocrit in post-renal transplant erythrocytosis (PRTE), which is distinctly associated with increased thrombosis risk 1
• ACE inhibition may induce apoptosis in erythroid precursor cells and has been shown to reduce hematocrit in COPD-associated erythrocytosis 1
• Theophylline has demonstrated efficacy in lowering hematocrit in both COPD and PRTE 1

Erythrocytapheresis (Preferred Alternative)

• Erythrocytapheresis is superior to traditional phlebotomy when available, particularly during the induction phase, as it requires fewer interventions and is cost-effective 1, 2, 3
• Allows for fewer hemodynamic changes compared to phlebotomy and returns valuable blood components 1
• Mild citrate reactions are common but manageable 1
• Represents the preferred treatment option in selected cases where standard phlebotomy is problematic 1, 2

Iron Chelation Therapy (Second-Line)

• Consider iron chelation (deferasirox) only when phlebotomy is not possible due to inaccessible veins, needle phobia, concomitant anemia, or life-threatening cardiac iron overload 1, 2
• Evidence is weak, and deferasirox should not be used in patients with advanced liver disease 1
• Associated with gastrointestinal side effects and impairment in kidney function 1
• Not approved for treatment of erythrocytosis by the European Medicines Agency 1

Cytoreductive Therapy for Polycythemia Vera

• High-risk polycythemia vera patients (age >60 years or prior thrombosis) require hydroxyurea in addition to phlebotomy and aspirin 4, 3
• Hydroxyurea causes severe myelosuppression and should not be initiated if bone marrow function is markedly depressed 5
• Monitor complete blood counts at baseline and throughout treatment; interrupt and reduce dose as necessary 5
• All polycythemia vera patients should receive low-dose aspirin (81-100 mg daily) to control microvascular disturbances unless contraindications exist 1, 4, 3

Critical Pitfalls to Avoid

Common Errors

• Never perform phlebotomy without meeting all three established criteria (Hgb >20 g/dL, Hct >65%, hyperviscosity symptoms) 1, 2, 3
• Never perform phlebotomy in the presence of dehydration or anemia—correct these conditions first 2, 3
• Never perform repeated phlebotomies without monitoring iron status, as creating iron deficiency paradoxically worsens symptoms and increases stroke risk 1, 2, 3
• Avoid aggressive phlebotomy in cyanotic congenital heart disease due to potential stroke risk 1
• Avoid overzealous phlebotomy in high oxygen-affinity hemoglobinopathy, as it provides no benefit and causes harm 1

Special Populations

• Pregnant women with mild to moderate iron overload: Phlebotomy can be paused for the duration of pregnancy in most patients, but avoid iron deficiency 1, 4
• Patients with advanced liver disease: Do not use iron chelation therapy 1
• Patients on antiretroviral drugs: Monitor for pancreatitis, hepatotoxicity, and peripheral neuropathy if hydroxyurea is used 5

Ongoing Surveillance

• Regularly monitor complete blood counts to track hemoglobin and hematocrit trends 2, 4
• Periodically assess iron status (ferritin, transferrin saturation) to prevent iron deficiency 2, 4
• Monitor for symptoms of hyperviscosity or thrombotic complications at each visit 2, 4
• Evaluate renal function, as chronic erythrocytosis can affect renal glomeruli and reduce glomerular filtration rate 1, 2
• Ensure adequate hydration before procedures involving contrast media to prevent uremia, oliguria, or anuria 1