Can secondary polycythemia cause ferritin depletion?

Secondary Polycythemia and Ferritin Depletion

Yes, secondary polycythemia can cause ferritin depletion, particularly in conditions of chronic hypoxia where increased erythropoiesis depletes iron stores over time. 1, 2

Pathophysiological Mechanism

Secondary polycythemia represents a non-clonal increase in red blood cell mass (RCM) that is often, but not always, mediated by erythropoietin (EPO) 1. This condition leads to iron depletion through several mechanisms:

1. Increased Erythropoiesis: The physiological response to hypoxia in secondary polycythemia drives increased red blood cell production, which requires substantial iron resources

2. Iron Utilization: The accelerated erythropoiesis in secondary polycythemia consumes available iron stores more rapidly than they can be replenished

3. Hepcidin Dysregulation: Despite iron deficiency that should suppress hepcidin (the master regulator of iron metabolism), inflammation that may accompany secondary polycythemia can counteract this suppression 2

Clinical Evidence

Several studies have documented the relationship between secondary polycythemia and ferritin depletion:

• Research has shown elevated serum transferrin receptor (sTfR) levels in both polycythemia vera and secondary polycythemia, with these elevations directly related to iron deficiency 3

• In patients with polycythemia vera, red cell ferritin content is significantly reduced and shows a positive correlation with hemoglobin level and percent transferrin saturation 4

• Iron deficiency is frequently encountered in cyanotic individuals with secondary erythrocytosis 1

Clinical Implications

The iron deficiency that develops in secondary polycythemia has important clinical consequences:

• Compromised Oxygen Transport: Iron deficiency causes a reduction of hemoglobin without a proportional change in hematocrit, compromising systemic oxygen transport without lowering viscosity 1

• Symptom Overlap: The symptoms of iron deficiency can mimic those of hyperviscosity, leading to diagnostic confusion 1

• Increased Risks: Consequences of iron deficiency in secondary polycythemia may include stroke and myocardial ischemia 1

Diagnostic Considerations

When evaluating patients with secondary polycythemia:

• Iron deficiency requires assessment of serum iron, ferritin, and transferrin levels, as mean corpuscular volume (MCV) is not a reliable screening test 1

• Limited data suggest that treatment of transferrin saturation <20% with iron supplementation until iron stores are replete can be done safely 1

• Reticulocyte maturity index (RMI) and the proportion of medium and high fluorescence reticulocytes (MFR+HFR) may be elevated in polycythemia with associated iron deficiency 5

Management Implications

Understanding the relationship between secondary polycythemia and ferritin depletion has important treatment implications:

• Iron supplementation may be necessary in patients with secondary polycythemia who develop iron deficiency

• Phlebotomy, which is sometimes used to manage secondary polycythemia, can exacerbate iron deficiency and should be used judiciously

• Monitoring iron status is important in the long-term management of patients with secondary polycythemia

The recognition of ferritin depletion in secondary polycythemia is essential for optimal patient management and prevention of complications related to both the underlying condition and the resultant iron deficiency.