How to manage iron deficiency in polycythemia (excessive red blood cell count)?

Management of Iron Deficiency in Polycythemia

In patients with polycythemia and confirmed iron deficiency, iron supplementation should be provided cautiously with close monitoring of hemoglobin/hematocrit levels, as iron repletion will increase red cell mass and potentially worsen hyperviscosity. 1

Key Diagnostic Considerations

Distinguish Between Polycythemia Types

• Polycythemia vera (PV) is a myeloproliferative neoplasm with >95% of patients having JAK2 mutations, requiring formal diagnosis per WHO criteria (hemoglobin >18.5 g/dL in men, >16.5 g/dL in women, plus JAK2 mutation). 1, 2
• Secondary erythrocytosis from chronic hypoxemia (cyanotic congenital heart disease) represents a physiological compensatory response to improve oxygen transport. 1
• Iron deficiency commonly coexists with both conditions but requires different management approaches. 1, 3

Confirm Iron Deficiency Properly

• Measure serum iron, ferritin, transferrin saturation, and evaluate red blood cell morphology—mean corpuscular volume (MCV) is unreliable in polycythemia. 1
• Transferrin saturation <20% confirms iron deficiency requiring treatment. 1
• Iron deficiency causes microcytic red cells with reduced oxygen-carrying capacity and deformability, increasing stroke risk despite elevated hematocrit. 1

Treatment Approach by Polycythemia Type

For Polycythemia Vera with Iron Deficiency

Iron supplementation in PV is controversial and requires individualized risk-benefit assessment:

• In routine clinical practice, a working diagnosis of PV can be made despite iron deficiency, even if WHO hemoglobin criteria aren't met. 1
• For research or clinical trial purposes, formal PV diagnosis requires demonstrating WHO criteria after iron replacement, though clinical prudence of this approach is left to physician discretion. 1
• Most PV patients are iron deficient at presentation and throughout their disease course, creating a physiological disconnect since both low iron and increased erythroferrone should suppress hepcidin. 3
• Therapeutic phlebotomy (standard PV treatment to maintain hematocrit <45%) exacerbates iron deficiency and contributes to non-hematological symptoms. 1, 2

If iron supplementation is pursued in PV:

• Oral iron administration frequently causes rapid, dramatic increases in red cell mass requiring close hemoglobin monitoring. 1
• Continue oral iron only until serum ferritin and/or transferrin saturation normalize, then discontinue. 1
• For patients intolerant of oral iron, use pulses of intravenous iron supplementation instead. 1
• In severe pruritus with documented iron deficiency, iron treatment for 2-3 weeks may provide symptom relief, though chronic iron treatment risks unacceptably high hemoglobin concentrations. 4
• Cytoreductive therapy (hydroxyurea, interferon, or ruxolitinib) works more effectively to reverse PV symptoms in iron-deficient versus iron-replete patients. 3, 2

For Secondary Erythrocytosis (Cyanotic Heart Disease) with Iron Deficiency

Iron deficiency in chronic hypoxemia is undesirable and should be corrected:

• Iron deficiency reduces oxygen-carrying capacity despite polycythemia and increases stroke risk due to production of poorly deformable microcytes. 1
• Confirm diagnosis with peripheral blood smear and serum ferritin or transferrin saturation. 1

Treatment strategy:

• Oral iron supplementation is the primary approach, but monitor hemoglobin closely as it frequently causes rapid red cell mass increases. 1
• Once serum ferritin and/or transferrin saturation normalize, discontinue iron supplementation. 1
• For patients intolerant of oral iron, use intravenous iron supplementation in pulses. 1
• Combined phlebotomy with oral iron therapy can maintain stable hematocrit while improving iron stores in patients with microcytic polycythemia and hematocrit approaching 70%. 5
• This combination approach improves serum iron levels, hematologic indices, clinical symptoms, and tissue oxygen delivery. 5

Critical Management Principles

Phlebotomy Considerations

• Repeated routine phlebotomies are contraindicated due to risk of iron depletion, decreased oxygen-carrying capacity, and stroke. 1
• Therapeutic phlebotomy is only indicated when hemoglobin >20 g/dL and hematocrit >65% with hyperviscosity symptoms and no dehydration. 1
• Always replace phlebotomy volume with equal dextrose or saline to relieve hyperviscosity symptoms. 1
• In PV, maintain hematocrit <45% with phlebotomy plus low-dose aspirin to reduce thrombosis risk. 1, 2

Hyperviscosity vs. Iron Deficiency Symptoms

• Symptoms of iron deficiency (headache, poor concentration, fatigue) mimic hyperviscosity symptoms. 1
• First-line therapy for suspected hyperviscosity: rehydrate with oral fluids or IV normal saline, then evaluate for iron deficiency. 1
• There is no clear correlation between viscosity, iron deficiency, and clinical symptoms—no "safe" hematocrit cutpoint exists. 1

Monitoring During Iron Therapy

• Monitor hemoglobin/hematocrit closely during iron supplementation as levels can rise rapidly. 1
• In PV patients, if iron treatment causes unacceptably high hemoglobin, discontinue iron (symptoms may recur). 4
• Avoid vitamin C supplements during phlebotomy or iron chelation as they accelerate iron mobilization. 1

Intravenous Iron Specifications (If Used)

• Administer iron sucrose 100-200 mg undiluted over 2-5 minutes or diluted in 100 mL 0.9% NaCl over ≥15 minutes. 6
• Monitor for hypersensitivity reactions for at least 30 minutes post-infusion. 6
• Avoid iron overload: monitor ferritin, transferrin saturation; do not administer with evidence of iron overload. 6