How should an adult patient with polycythemia and elevated ferritin be managed?

Management of Adult Polycythemia with Elevated Ferritin

In an adult patient with polycythemia and elevated ferritin, phlebotomy should only be performed if hemoglobin exceeds 20 g/dL AND hematocrit exceeds 65% with documented hyperviscosity symptoms (headache, fatigue, poor concentration) in the absence of dehydration—otherwise, avoid routine phlebotomy as it risks iron depletion and paradoxically worsens oxygen-carrying capacity. 1, 2

Initial Diagnostic Approach

Distinguish primary from secondary polycythemia first:

• Measure serum erythropoietin (EPO) level, though recognize that EPO can be elevated even in polycythemia vera (PV), so this alone is insufficient for diagnosis 3, 4
• Test for JAK2 V617F mutation to confirm PV, as this is the definitive diagnostic marker 3, 5, 6
• Assess hydration status immediately, as dehydration causes relative erythrocytosis and must be corrected before any intervention 1, 2
• Evaluate for secondary causes: smoking history, chronic lung disease, cardiac disorders, renal pathology, or malignancy-associated EPO production 2, 4

Interpreting the Elevated Ferritin

The elevated ferritin in this context requires careful interpretation:

• In polycythemia vera, ferritin may be elevated as an acute-phase reactant despite functional iron deficiency 1
• Check transferrin saturation and serum iron levels—if transferrin saturation is <20%, this suggests functional iron deficiency despite elevated ferritin 1
• Consider hemochromatosis screening (HFE gene mutation) if ferritin remains persistently elevated with high transferrin saturation, as PV and hereditary hemochromatosis can coexist 6
• Iron overload itself (from hemochromatosis or hyperferritinaemia) can cause pruritus, which may be confused with PV-related symptoms 1

Management Strategy Based on Hemoglobin/Hematocrit Levels

For hemoglobin ≤20 g/dL or hematocrit ≤65%:

• Do NOT perform phlebotomy, as repeated phlebotomies cause iron depletion, decreased oxygen-carrying capacity, and increased stroke risk 1, 2
• Ensure adequate hydration, particularly before any procedures or long-distance travel 1, 2
• Monitor with regular complete blood counts 2

For hemoglobin >20 g/dL AND hematocrit >65% WITH hyperviscosity symptoms:

• Perform therapeutic phlebotomy (500 mL weekly or biweekly as tolerated) 1
• Check hemoglobin/hematocrit before each phlebotomy and allow no more than 20% decrease from prior level 1
• Target hematocrit <45% in confirmed PV patients 3
• Monitor ferritin every 10-12 phlebotomies; stop frequent phlebotomy when ferritin reaches 50-100 μg/L 1, 2

Specific Management for Polycythemia Vera (if JAK2 positive)

Once PV is confirmed:

• Initiate low-dose aspirin (unless contraindications exist) to reduce thrombotic risk, which is significantly elevated with JAK2 mutation 2, 4, 5
• Be vigilant for thrombotic complications, including unusual sites like cerebral venous thrombosis, which can present with headache, visual changes, or neurological symptoms 5
• Consider anticoagulation if thrombotic event occurs 3, 5
• Phlebotomy remains first-line treatment for low-risk PV patients 3, 4

If Hemochromatosis is Confirmed (HFE mutation positive)

For true iron overload with ferritin >1000 μg/L:

• Weekly phlebotomy is indicated regardless of hemoglobin level, targeting ferritin 50-100 μg/L 1
• Avoid vitamin C supplements (limit to <500 mg/day if needed) as this can worsen iron-related organ damage 1
• Avoid iron-containing vitamin preparations and iron-fortified foods 1
• No specific dietary iron restriction is necessary beyond avoiding supplements 1
• Screen for cirrhosis if ferritin >1000 μg/L with liver biopsy or transient elastography 1

Critical Pitfalls to Avoid

• Never perform routine phlebotomies without meeting strict criteria (Hgb >20 g/dL, Hct >65%, symptoms present, no dehydration), as this is the most common error leading to iatrogenic iron deficiency 1, 2
• Do not assume low EPO is required for PV diagnosis—EPO can be elevated in confirmed JAK2-positive PV 3
• Recognize that ferritin >1000 μg/L may represent acute inflammation rather than true iron overload—check transferrin saturation to clarify 1
• Iron deficiency from excessive phlebotomy paradoxically worsens symptoms by reducing red cell deformability and oxygen delivery despite lower hematocrit 1, 2

Monitoring Protocol

• Complete blood count every 2-4 weeks during active phlebotomy, then every 3-6 months once stable 2
• Ferritin and iron studies every 10-12 phlebotomies or every 3-6 months 1, 2
• Assess for hyperviscosity symptoms (headache, fatigue, visual changes, erythromelalgia, pruritus) at each visit 2, 7
• Monitor for thrombotic complications, particularly in JAK2-positive patients 2, 5