How do I treat anemia with low ferritin (iron storage) and high serum iron levels?

Management of Anemia with Low Ferritin and High Serum Iron

In patients with anemia presenting with low ferritin and high serum iron levels, iron-refractory iron deficiency anemia (IRIDA) due to TMPRSS6 gene mutations should be considered as the primary diagnosis and treated with intravenous iron supplementation. 1

Diagnostic Approach

When encountering this unusual pattern of laboratory values, consider the following diagnostic steps:

1. Confirm the pattern: Verify the presence of:

   • Microcytic anemia
   • Low ferritin (indicating depleted iron stores)
   • High serum iron
   • Low transferrin saturation (TSAT)

2. Key diagnostic tests:

   • Complete iron studies (serum iron, TIBC, TSAT, ferritin)
   • Serum hepcidin levels (elevated in IRIDA)
   • Calculate hepcidin:TSAT ratio (elevated ratio suggests IRIDA)
   • TMPRSS6 mutation analysis if IRIDA is suspected 1

3. Rule out other causes:

   • Inflammatory conditions (check C-reactive protein)
   • Blood loss (gastrointestinal, menstrual)
   • Malabsorption disorders
   • Hemolysis

Treatment Algorithm

First-line Treatment:

1. Initial oral iron trial:
   • Trial of oral iron combined with ascorbic acid (vitamin C)
   • Monitor hemoglobin response after 8-10 weeks 1, 2

If inadequate response to oral iron:

1. Switch to intravenous iron therapy:
   • Indicated for IRIDA patients with insufficient response to oral iron
   • Calculate total iron deficit based on hemoglobin deficit and iron stores
   • Administer in divided doses every 3-7 days until total dose is reached 1

Choice of IV iron formulation:

• Ferric carboxymaltose (Injectafer): Allows for higher single doses with fewer administrations 3
• Iron sucrose (Venofer): Well-established safety profile, may require more frequent dosing 4

Monitoring during treatment:

• Monitor serum ferritin levels regularly
• Target ferritin should not exceed 500 μg/L to avoid iron overload 1
• Repeat hemoglobin, MCV, ferritin, and TSAT after 8-10 weeks of treatment 2

Special Considerations

IRIDA (Iron-Refractory Iron Deficiency Anemia)

• Rare genetic disorder caused by TMPRSS6 mutations
• Characterized by:
  • Microcytic anemia
  • Low TSAT
  • Normal or reduced serum ferritin
  • Poor response to oral iron
  • Partial response to IV iron 1

Family Screening

• IRIDA has an autosomal recessive inheritance pattern
• Screen relatives (siblings and spouse if consanguinity) for IRIDA phenotype
• Genetic counseling recommended for patients with pathogenic TMPRSS6 mutations 1

Potential Pitfalls

1. Misdiagnosis: The combination of low ferritin and high serum iron is unusual and may lead to diagnostic confusion.

2. Inappropriate iron supplementation: Administering iron when not indicated can lead to iron overload. Long-term daily oral or IV iron supplementation with normal/high ferritin is potentially harmful. 2

3. Inadequate monitoring: Failure to monitor ferritin during treatment may lead to iron overload. Serum ferritin should not exceed 500 μg/L during treatment. 1

4. Overlooking genetic causes: IRIDA is rare but should be considered when this unusual pattern of iron studies is present, especially with poor response to oral iron. 1, 5

5. Excessive phlebotomy: In patients with hemochromatosis, excessive therapeutic phlebotomy can paradoxically cause iron deficiency with low ferritin despite previously high iron levels. 6

By following this approach, you can effectively diagnose and manage patients with the unusual presentation of anemia with low ferritin and high serum iron levels.