What is the management and treatment approach for a patient with erythrocytosis, characterized by an increased red blood cell mass?

Management of Erythrocytosis

Ensure adequate hydration first, assess iron status immediately, and avoid routine phlebotomy—reserving therapeutic phlebotomy only for patients with hemoglobin >20 g/dL, hematocrit >65%, persistent hyperviscosity symptoms after rehydration, and confirmed iron sufficiency. 1, 2

Initial Assessment and Diagnostic Approach

Distinguish Primary from Secondary Erythrocytosis

• Order JAK2 mutation testing and serum erythropoietin level as your first diagnostic step to differentiate polycythemia vera from secondary causes 3
• If JAK2 is positive with low EPO, the diagnosis is polycythemia vera requiring hematology referral 3
• If JAK2 is negative with elevated EPO, pursue secondary causes including hypoxemia, cyanotic heart disease, sleep apnea, renal tumors, or congenital oxygen-sensing pathway defects 2, 3

Evaluate Iron Status Immediately

• Check serum ferritin, transferrin saturation, and obtain a peripheral blood smear to assess for microcytic hypochromic cells 1, 3
• Iron deficiency is the strongest independent predictor of cerebrovascular events—not the hematocrit level itself 4
• Transferrin saturation <20% requires iron supplementation until stores are replete 1
• Mean corpuscular volume is unreliable for screening iron deficiency in this population 1

First-Line Management Strategy

Hydration as Primary Therapy

• Rehydrate all patients with suspected hyperviscosity using oral fluids or intravenous normal saline before considering any other intervention 1, 2
• Many symptoms attributed to hyperviscosity (headache, dizziness, fatigue, visual disturbances, paresthesias) resolve with adequate hydration alone 1, 4, 2

Address Underlying Causes

• Treat the root cause of secondary erythrocytosis: optimize oxygenation in cyanotic heart disease, manage sleep apnea with CPAP, address chronic lung disease, or discontinue erythropoietin-stimulating agents if overused 2, 5
• In cyanotic congenital heart disease, recognize that erythrocytosis is a physiological adaptive response to chronic hypoxemia attempting to improve tissue oxygen delivery 1

When to Consider Therapeutic Phlebotomy

Strict Criteria Must Be Met

Perform phlebotomy ONLY when ALL of the following are present: 1, 2

• Hemoglobin exceeds 20 g/dL AND hematocrit exceeds 65%
• Persistent symptoms of hyperviscosity (headache, visual changes, fatigue, poor concentration) after adequate rehydration
• No evidence of dehydration
• No iron deficiency (confirmed by iron studies)
• Evidence of end-organ damage attributable to hyperviscosity (myocardial ischemia, transient ischemic attack, stroke)

Phlebotomy Protocol

• Remove 1 unit of blood (400-500 mL) with simultaneous equal volume replacement using isotonic saline or dextrose solution 2
• Administer replacement fluids concurrently with blood removal to maintain intravascular volume 2
• Monitor iron status after phlebotomy to prevent iatrogenic iron deficiency 2

Critical Pitfalls to Avoid

Do Not Perform Routine Phlebotomy

• Routine or repeated phlebotomies without meeting strict criteria cause iron deficiency, which paradoxically worsens symptoms and increases stroke risk 1, 4, 2
• Iron-deficient red cells become rigid, less deformable, and have reduced oxygen-carrying capacity despite lower hematocrit 1, 4
• There is no "safe" hematocrit cutoff that justifies prophylactic phlebotomy 1
• The severity of symptoms does not correlate with measured hematocrit levels 1

Understand the Bleeding-Thrombosis Paradox

• Patients with erythrocytosis face simultaneous bleeding and thrombotic risks due to platelet dysfunction, coagulation abnormalities, and depleted von Willebrand multimers 1, 4
• Hemostatic abnormalities occur in up to 20% of cyanotic congenital heart disease patients 1, 2
• Currently available data do not support routine anticoagulation or aspirin due to increased bleeding risk 4

Special Populations

Cyanotic Congenital Heart Disease

• Recognize compensated versus decompensated erythrocytosis: stable hemoglobin in an iron-replete state indicates equilibrium, while rising hematocrit suggests failure of homeostasis 1
• Aortic oxygen saturations <75% may trigger decompensated erythrocytosis 1
• Monitor for complications including cerebrovascular accidents, coronary events, hemoptysis (reported in up to 100% of Eisenmenger patients), and hyperuricemia with calcium bilirubinate gallstones 1, 4

Polycythemia Vera

• Refer to hematology for cytoreductive therapy with hydroxyurea or other agents 3
• Consider low-dose aspirin for thrombosis prevention in polycythemia vera, but not in secondary erythrocytosis 6

Monitoring Recommendations

• Follow complete blood counts regularly to track hemoglobin and hematocrit trends 2
• Assess iron status periodically to prevent deficiency, especially after any phlebotomy 2, 3
• Monitor for hyperviscosity symptoms and thrombotic complications at each visit 2
• Evaluate renal function as chronic erythrocytosis can affect renal glomeruli 2