Should iron supplements be given to patients with polycythemia?

Iron Supplementation in Polycythemia

Iron supplementation should generally be avoided in patients with polycythemia unless there is documented severe tissue iron deficiency associated with detrimental symptoms. 1

Understanding Iron Status in Polycythemia

Polycythemia is characterized by increased red blood cell production, and treatment often includes phlebotomy to control hematocrit levels. This therapeutic approach frequently leads to iron deficiency as a consequence of treatment.

• Patients with polycythemia vera (PV) commonly develop iron deficiency due to repeated phlebotomies used to control hematocrit levels 1
• Iron deficiency may manifest with symptoms such as pruritus (itching), pica, mouth paresthesia, esophagitis, and restless legs syndrome 1
• A correlation has been observed between active pruritus and low mean corpuscular volume, suggesting a potential pathogenetic role for iron deficiency in PV-associated symptoms 1

Iron Supplementation Recommendations

The decision to provide iron supplementation in polycythemia requires careful consideration of risks versus benefits:

• Iron supplementation should generally be avoided in patients with polycythemia as it can worsen the underlying condition by promoting further red cell production 1
• Iron supplementation should only be considered in cases of documented severe tissue iron deficiency with detrimental symptoms such as pica, mouth paresthesia, esophagitis, or restless legs syndrome 1
• If iron supplementation is deemed necessary, it should be accompanied by appropriate cytoreductive therapy to prevent undesired hematocrit elevation 1

Effects of Iron Status on Blood Viscosity

The relationship between iron deficiency and blood viscosity in polycythemia has been studied with mixed results:

• Some research suggests that iron deficiency in treated PV does not increase whole blood viscosity 2
• Other studies indicate that iron deficiency can lead to a significant increase in whole blood viscosity in polycythemic patients, which can be corrected by simultaneous treatment with iron and venesection 3
• In hypoxic polycythemia specifically, treating coexisting iron deficiency may increase hemoglobin concentration without altering whole blood viscosity, potentially improving oxygen availability to tissues 3

Management Approach

For patients with polycythemia requiring iron management:

• Phlebotomy remains the mainstay of therapy for polycythemia vera, with a target hematocrit below 45% 1
• Monitor serum ferritin levels during phlebotomy treatment; during the induction phase, measure ferritin monthly or after every 4th phlebotomy 1
• When ferritin decreases below 200 μg/L, more frequent monitoring (every 1-2 sessions) is recommended 1
• It is advisable to periodically check plasma folate and cobalamin levels, especially in patients requiring numerous venesections, and provide vitamin supplementation if necessary 1

Special Considerations

For Symptomatic Iron Deficiency:

• If iron supplementation is deemed necessary due to severe symptomatic iron deficiency, concurrent cytoreductive therapy should be considered to prevent hematocrit elevation 1
• In patients with PV who have intractable pruritus associated with iron deficiency, interferon-alpha (IFN-α) may be considered as a treatment option rather than iron supplementation 1

For Patients on JAK Inhibitors:

• In patients receiving ruxolitinib (a JAK1/JAK2 inhibitor), improvements in iron deficiency markers have been observed, which may reduce the need for iron supplementation 4
• Ruxolitinib treatment has been associated with improvements in concentration problems, cognitive function, dizziness, fatigue, headaches, and inactivity in PV patients with baseline iron deficiency 4

Monitoring Recommendations

When managing iron status in polycythemia:

• Regular monitoring of complete blood count, serum ferritin, and transferrin saturation is essential 1
• Avoid indiscriminate use of iron replacement therapy, as it has not been consistently effective in treating PV-associated symptoms and may worsen the underlying condition 1
• If iron supplementation is provided, closely monitor hematocrit levels for undesired elevation that would indicate the need for cytoreductive therapy 1