How to manage a patient with normal ferritin (iron storage protein) levels but decreased iron levels, indicating iron deficiency without significant store depletion?

Management of Normal Ferritin with Decreased Iron Levels

Patients with normal ferritin but decreased serum iron levels should be treated for functional iron deficiency with oral iron supplementation, as this pattern indicates inadequate iron availability for erythropoiesis despite apparently adequate iron stores.

Understanding the Laboratory Pattern

This pattern represents functional iron deficiency, which occurs when:

• Serum iron is low (decreased iron levels)
• Ferritin is normal (indicating apparently adequate iron stores)
• Transferrin saturation (TSAT) is typically low (<20%)

This laboratory pattern indicates that despite having seemingly adequate iron stores (normal ferritin), there is insufficient iron available for erythropoiesis, which can negatively impact hemoglobin production and potentially lead to anemia if left untreated 1.

Diagnostic Approach

1. Calculate transferrin saturation (TSAT):

   • TSAT = (serum iron ÷ total iron binding capacity) × 100
   • TSAT <20% confirms inadequate iron availability for erythropoiesis 2

2. Consider inflammatory status:

   • Ferritin is an acute phase reactant that increases with inflammation
   • Normal ferritin may actually represent relative iron deficiency in inflammatory states 1
   • In inflammatory conditions, ferritin up to 100 μg/L may still represent iron deficiency 1

3. Additional testing to consider:

   • Complete blood count with red cell indices
   • Reticulocyte hemoglobin content (<30 pg suggests iron-restricted erythropoiesis)
   • Soluble transferrin receptor (elevated in true iron deficiency) 1

Treatment Algorithm

1. First-line therapy: Oral iron supplementation

   • Ferrous sulfate 325 mg daily (providing 65 mg elemental iron) 1
   • Take on an empty stomach if tolerated
   • Take with vitamin C (500 mg) to enhance absorption
   • Avoid taking with tea, coffee, calcium, or antacids 1

2. Consider IV iron if:

   • Oral iron is not tolerated
   • Inadequate response to oral therapy after 4-8 weeks
   • Ferritin remains below target despite oral supplementation
   • Rapid correction is needed due to severe symptoms 1, 3

3. Treatment target:

   • Ferritin level of at least 50-100 μg/L to fully replenish iron stores 1
   • TSAT >20% to ensure adequate iron availability for erythropoiesis 2

Monitoring Response

1. Short-term monitoring:

   • Check ferritin and TSAT after 4-8 weeks of treatment 1
   • If no improvement in iron parameters, consider:
     • Poor compliance
     • Malabsorption
     • Ongoing blood loss
     • Inflammatory iron block

2. Long-term monitoring:

   • Continue monitoring every 6-12 months after successful treatment
   • More frequent monitoring if risk factors persist 1

Special Considerations

1. Chronic inflammatory conditions:

   • Higher ferritin cutoffs (up to 100 μg/L) should be used to diagnose iron deficiency 1
   • Consider IV iron if oral iron is ineffective due to hepcidin-mediated iron sequestration 4

2. Chronic kidney disease:

   • Functional iron deficiency is common with normal/high ferritin but low TSAT
   • Consider IV iron with TSAT <20% even if ferritin is normal 2, 1

3. Heart failure:

   • Low TSAT (<20%) appears to be a more reliable indicator of iron deficiency than ferritin
   • Patients with TSAT <20% show greater benefit from iron supplementation 4

Dietary Recommendations

• Increase consumption of iron-rich foods, particularly heme iron sources (red meat, seafood)
• Include vitamin C-rich foods with meals containing non-heme iron
• Limit tea and coffee consumption around mealtimes 1
• Avoid iron-fortified foods until iron status normalizes 2

Common Pitfalls to Avoid

1. Relying solely on ferritin without measuring TSAT:

   • Ferritin alone can miss functional iron deficiency
   • TSAT <20% is a better indicator of inadequate iron availability 2, 1, 4

2. Ignoring inflammatory status:

   • Inflammation elevates ferritin independent of iron stores
   • "Normal" ferritin may actually represent relative iron deficiency 1

3. Stopping treatment too early:

   • Continue treatment until both ferritin and TSAT reach target levels
   • Early discontinuation may lead to recurrence 1

4. Missing ongoing blood loss:

   • Persistent iron deficiency despite adequate supplementation suggests ongoing blood loss
   • Consider gastrointestinal evaluation, especially in older adults 5