How do you treat a patient with serum ferritin levels less than 50 μg/L?

Treatment for Serum Ferritin <50 μg/L

For patients with serum ferritin <50 μg/L, oral iron supplementation is the first-line treatment, with intravenous iron reserved for those with poor response, intolerance, or specific clinical conditions.

Diagnosis Confirmation

• Serum ferritin <50 μg/L is diagnostic of iron deficiency, with a positive predictive value of 100% 1
• Low ferritin is the most specific marker of iron deficiency, even in the absence of anemia
• Consider additional testing if diagnosis is uncertain:
  • Transferrin saturation <20% supports iron deficiency diagnosis
  • Complete blood count to assess for anemia

Treatment Algorithm

First-Line Treatment: Oral Iron

1. Dosing options:

   • Ferrous sulfate 325 mg (65 mg elemental iron) daily or on alternate days 2
   • Alternate-day dosing may improve absorption by reducing hepcidin elevation 3
   • Single morning dose is preferable to divided doses (improves absorption) 3

2. Duration:

   • Continue until ferritin reaches 50-100 μg/L target range 4
   • Typically requires 3-6 months of therapy

3. Monitoring:

   • Check ferritin and hemoglobin after 4-8 weeks of therapy
   • Continue monitoring every 3 months until target ferritin is reached 4

Second-Line Treatment: Intravenous Iron

Indications for IV iron (when oral iron is insufficient):

• Intolerance to oral iron
• Poor absorption (celiac disease, post-bariatric surgery)
• Ongoing blood loss
• Chronic inflammatory conditions (CKD, heart failure, IBD, cancer)
• Second/third trimester pregnancy with severe deficiency 2

Dosing for IV iron (ferric carboxymaltose):

• For patients ≥50 kg: 750 mg IV in two doses separated by at least 7 days (total 1,500 mg) 5
• For patients <50 kg: 15 mg/kg IV in two doses separated by at least 7 days 5

Special Considerations

Factors Affecting Treatment Response

• Proton pump inhibitors: May reduce oral iron absorption; consider higher doses, longer duration, or IV iron in patients on PPIs 6
• Inflammation: May reduce iron absorption and raise ferritin (falsely suggesting adequate stores)
• Diet: Advise patients to avoid:
  • Iron supplements and iron-fortified foods
  • Supplemental vitamin C near meals (increases iron absorption)
  • Alcohol (especially during iron depletion phase) 4

Common Pitfalls

1. Misinterpreting ferritin levels:

   • Ferritin is an acute phase reactant; inflammation can falsely elevate levels
   • In inflammatory states, iron deficiency may exist even with ferritin >50 μg/L 1

2. Inadequate investigation of cause:

   • Always investigate underlying cause of iron deficiency
   • Common causes: menstrual bleeding, gastrointestinal blood loss, malabsorption, pregnancy

3. Suboptimal dosing strategies:

   • Divided daily doses increase hepcidin and reduce absorption
   • Once-daily or alternate-day dosing is more effective 3

4. Premature discontinuation:

   • Continue treatment until ferritin reaches target range (50-100 μg/L) 4
   • Replenishing iron stores takes longer than correcting hemoglobin

Lifestyle Modifications

• Increase dietary iron intake (red meat, leafy greens, legumes)
• Consume vitamin C-rich foods with meals to enhance non-heme iron absorption
• Avoid tea, coffee, calcium supplements, and dairy products within 2 hours of iron supplements
• Limit alcohol intake, especially during iron depletion phase 4

By following this treatment algorithm and addressing common pitfalls, most patients with ferritin <50 μg/L can successfully replenish their iron stores and resolve associated symptoms.