Iron Levels in Polycythemia
Iron levels are characteristically LOW, not elevated, in polycythemia vera (PV), with virtually all PV patients being iron deficient at presentation and/or during the course of their disease. 1
Iron Status in Polycythemia Vera
Iron deficiency is a hallmark feature of PV, not iron elevation. The co-existence of iron deficiency and polycythemia represents a physiological disconnect that is central to understanding this disease 1:
- Decreased bone marrow iron stores are a characteristic finding on bone marrow examination in PV patients 2, 3
- Microcytosis from iron deficiency is recognized as a PV-related diagnostic feature that should prompt evaluation for polycythemia vera even when hematocrit is only borderline elevated 2, 3
- Serum ferritin levels are typically low in PV patients, reflecting depleted iron stores 1
Mechanisms of Iron Deficiency in PV
The iron deficiency in PV occurs through multiple mechanisms 1:
- Therapeutic phlebotomy, the most common treatment approach for reducing thrombotic complications, directly exacerbates iron deficiency by removing iron-containing red blood cells 1
- Dysregulated iron metabolism appears to be an intrinsic component of PV pathobiology, with insufficiently suppressed hepcidin levels given the degree of iron deficiency 1
- Increased iron utilization occurs due to the expanded erythroid mass and ongoing erythropoiesis 1
Clinical Implications
Iron deficiency in PV has important therapeutic consequences 1:
- Cytoreductive therapy works more effectively to reverse PV-associated symptoms in iron-deficient relative to iron-replete patients 1
- Iron replacement therapy is generally discouraged in PV because it may increase red cell mass and worsen polycythemia 2
- However, in select cases with severe pruritus and documented iron deficiency, cautious short-term iron supplementation (2-3 weeks after symptom resolution) may provide symptomatic benefit, though this requires close monitoring of hemoglobin levels 4
Contrast with Secondary Polycythemia
In secondary polycythemia due to chronic hypoxia, iron status differs 5:
- Iron supplementation is often required to maintain the physiologically appropriate compensatory polycythemia that improves oxygen-carrying capacity 5
- Microcytic polycythemia in hypoxic patients may benefit from combined phlebotomy with oral iron therapy to maintain stable hematocrit while improving iron stores and tissue oxygen delivery 5
Critical Diagnostic Point
The presence of microcytosis or iron deficiency in a patient with elevated hemoglobin/hematocrit should raise suspicion for PV rather than secondary polycythemia, as this combination is characteristic of the former 2, 3. This finding should prompt JAK2 mutation testing and bone marrow examination rather than assuming a reactive process 3.