Is it safe to start iron supplementation in patients with polycythemia?

Iron Supplementation in Polycythemia Vera: Generally Contraindicated

Iron supplementation should be avoided in patients with polycythemia vera (PV) as indiscriminate use is explicitly discouraged, though rare exceptions exist for severe iron deficiency-related symptoms that persist despite adequate hematological control. 1

Primary Management Strategy

The standard approach to PV management intentionally creates and maintains iron deficiency through therapeutic phlebotomy:

• All PV patients should undergo phlebotomy to maintain hematocrit below 45%, which is the primary treatment to reduce thrombotic risk 1
• Phlebotomy inherently depletes iron stores, and this iron deficiency is a therapeutic goal rather than a complication to be corrected 1
• The iron-deficient state helps limit erythrocytosis and maintain hematocrit control 2

The Physiological Paradox

PV presents a unique situation where iron deficiency coexists with polycythemia:

• Virtually all PV patients are iron deficient at presentation or during disease course 2
• This represents dysregulated iron metabolism that is integral to PV pathobiology 2
• Iron deficiency in PV actually helps prevent dangerously elevated hematocrit levels that increase thrombotic risk 1

Rare Exceptions for Iron Supplementation

Iron may be considered only in highly specific circumstances:

• Documented severe tissue iron deficiency with detrimental symptoms including pica, mouth paresthesia, esophagitis, or restless legs syndrome 1
• Severe, intractable pruritus that persists despite adequate hematological control and is associated with confirmed iron deficiency 1, 3

Critical Caveats When Iron Is Given

If iron supplementation is initiated for severe symptoms:

• Treatment should continue for only 2-3 weeks after symptoms resolve 3
• Close monitoring of hematocrit is mandatory as iron will increase red cell mass 3
• If hematocrit rises to unacceptable levels, iron must be stopped immediately 3
• Cytoreductive therapy should be initiated if hematocrit cannot be controlled with phlebotomy alone 1

Why Iron Is Contraindicated

The evidence clearly demonstrates multiple risks:

• Iron supplementation directly increases hemoglobin and hematocrit levels, potentially reaching dangerous levels (approaching 70%) that cause hyperviscosity and vascular sludging 4
• Elevated hematocrit above 45% significantly increases thrombotic events (hazard ratio 3.91) 1
• Iron replacement has not been consistently effective for treating PV-associated symptoms like pruritus 1
• Most iron deficiency-related symptoms in PV improve with cytoreductive therapy (hydroxyurea or ruxolitinib) rather than iron supplementation 5

Preferred Alternative Approaches

Instead of iron supplementation, address symptoms through:

• Cytoreductive therapy (hydroxyurea or ruxolitinib) for high-risk patients, which works more effectively in iron-deficient patients 2, 5
• Interferon-alpha for intractable pruritus (up to 81% response rate), which reduces phlebotomy needs and lessens iron deficiency 1
• Paroxetine (selective serotonin reuptake inhibitor) for pruritus (>80% response rate) 1
• Continued phlebotomy with low-dose aspirin as foundational therapy 1

Common Pitfall to Avoid

The most critical error is reflexively treating iron deficiency in PV as you would in other conditions. Iron deficiency in PV is therapeutic, not pathologic 1. Correcting it undermines hematocrit control and increases thrombotic risk, which directly impacts mortality—the primary outcome that matters most 1.