What is the appropriate management for a patient with elevated storage iron and normal ferritin levels?

Management of Elevated Storage Iron with Normal Ferritin

No Treatment Required - Monitor Only

With a ferritin level of 33 ng/mL (well below 300 ng/mL for men or 200 ng/mL for women), no iron removal therapy is indicated despite the increased bone marrow storage iron, as treatment thresholds are based on serum ferritin levels and transfusion burden, not bone marrow iron staining alone. 1, 2

Understanding the Discrepancy

The finding of increased bone marrow storage iron (3+) with a normal-to-low ferritin level (33 ng/mL) represents a discordant picture that requires careful interpretation:

• Bone marrow iron staining reflects local iron stores but does not necessarily correlate with total body iron burden or the need for intervention 1
• Serum ferritin remains the primary biomarker for determining treatment thresholds in iron overload conditions 1, 2, 3
• This discrepancy may indicate ineffective erythropoiesis, where iron is trapped in the marrow but not effectively utilized, or may reflect technical/sampling variation 4

Treatment Thresholds Not Met

Based on established guidelines, iron removal therapy should only be initiated when specific criteria are met:

• For hereditary hemochromatosis: Treatment begins at ferritin ≥300 μg/L in men or ≥200 μg/L in women, regardless of symptoms 2, 3
• For transfusional iron overload: Chelation therapy is indicated when ferritin reaches ≥1,000 ng/mL or with transfusion requirements of ≥2 units/month for >1 year 5
• Your patient's ferritin of 33 ng/mL is far below any treatment threshold and actually approaches the lower end of normal 1, 2

Recommended Management Approach

Immediate Actions

• Verify the ferritin result with repeat testing to ensure accuracy, as this low level contradicts the bone marrow findings 1
• Measure transferrin saturation to assess functional iron status and rule out hereditary hemochromatosis (threshold >45% in women, >50% in men) 1, 2
• Review transfusion history to determine if this represents transfusional iron overload (requires ≥100 mL/kg packed RBCs or ~20 units) 6

Diagnostic Evaluation

• Assess for causes of ineffective erythropoiesis such as myelodysplastic syndrome, thalassemia, or sideroblastic anemia, which can cause marrow iron accumulation without elevated ferritin 5
• Evaluate liver function tests (ALT, AST, bilirubin) to assess for occult liver disease that might affect ferritin levels 1, 2
• Consider genetic testing for HFE mutations (C282Y, H63D) if transferrin saturation is elevated, though unlikely with this ferritin level 1, 2

Monitoring Strategy

• Recheck serum ferritin in 3-6 months to establish a trend, as a single low value may not reflect the complete picture 1, 3
• Monitor hemoglobin and complete blood count to assess for anemia or other hematologic abnormalities 7, 4
• If ferritin remains <50 μg/L, consider that iron stores may actually be depleted despite the bone marrow appearance 7, 4

Critical Pitfalls to Avoid

• Do not initiate phlebotomy or chelation therapy based solely on bone marrow iron staining when ferritin is normal or low, as this could induce iron deficiency anemia 1, 7, 4
• Avoid iron supplementation until the discrepancy is explained, as this could worsen occult iron overload if present 1, 3
• Do not overlook the possibility of laboratory error or specimen mislabeling given the contradictory findings 4
• Recognize that ferritin can be falsely low in the setting of severe malnutrition, hypothyroidism, or vitamin C deficiency, though these are uncommon 3

When to Reconsider Treatment

Treatment would only become appropriate if:

• Ferritin rises to ≥300 μg/L (men) or ≥200 μg/L (women) with confirmed iron overload 2, 3
• Patient develops transfusion dependence requiring ≥2 units/month for >1 year with ferritin ≥1,000 ng/mL 5, 6
• Evidence of end-organ damage from iron deposition appears (cardiac, hepatic, endocrine dysfunction) requiring organ preservation 5