At what serum ferritin level should iron supplements be started?

Iron Supplementation Guidelines Based on Serum Ferritin Levels

Iron supplements should be started when serum ferritin levels fall below 30 ng/mL in non-inflammatory conditions, or below 100 ng/mL in patients with inflammation or cancer. 1

Assessment of Iron Status

• Serum ferritin reflects storage iron, while transferrin saturation (TSAT) reflects iron that is readily available for erythropoiesis 1
• In non-inflammatory conditions, serum ferritin <30 ng/mL indicates absolute iron deficiency 1
• In patients with inflammation, cancer, or inflammatory bowel disease, the ferritin cutoff should be raised to 100 ng/mL due to ferritin's role as an acute phase reactant 1
• Iron deficiency is reflected by low transferrin saturation (TSAT <20%) and can be further characterized as:
  • Absolute iron deficiency: depleted iron stores with serum ferritin <30 ng/mL 1
  • Functional iron deficiency: adequate iron stores with normal or increased serum ferritin but impaired iron utilization 1

Specific Recommendations by Patient Population

Patients with Inflammatory Conditions (IBD, Cancer, CKD)

• Start iron supplementation when ferritin is <100 ng/mL in patients with active inflammation 1
• For patients with inflammatory bowel disease with serum ferritin between 30-100 ng/mL, a combination of true iron deficiency and anemia of chronic disease is likely 1
• In chronic kidney disease patients, maintain serum ferritin at >100 ng/mL and TSAT >20% 1
• After successful treatment of iron deficiency anemia with intravenous iron in IBD patients, re-treatment should be initiated when serum ferritin drops below 100 μg/L 1

Patients without Inflammatory Conditions

• Start iron supplementation when ferritin is <30 ng/mL in patients without inflammation 1
• In healthy individuals, ferritin levels <12 μg/L indicate depleted iron stores 1
• Regular blood donors may benefit from iron supplementation when ferritin levels fall below 15 μg/L 2

Route of Administration

• Oral iron should be considered as first-line treatment in:

  • Patients with mild anemia 1
  • Clinically inactive disease 1
  • No previous intolerance to oral iron 1

• Intravenous iron should be considered as first-line treatment in:

  • Patients with clinically active inflammatory disease 1
  • Previous intolerance to oral iron 1
  • Hemoglobin below 100 g/L 1
  • Patients requiring erythropoiesis-stimulating agents 1
  • Hemodialysis patients (as oral iron is often inadequate) 1

Monitoring Response

• Monitor ferritin levels every 3 months in patients with active disease 1
• Monitor ferritin levels every 6-12 months in patients in remission or with mild disease 1
• Consider other markers of iron status such as TSAT, hemoglobin content in reticulocytes, and percentage of hypochromic RBCs when evaluating response 1

Common Pitfalls and Caveats

• Serum ferritin is an acute phase reactant and can be elevated in inflammatory conditions, masking iron deficiency 1
• A ferritin level >50 μg/L does not automatically exclude iron deficiency in patients with inflammation 3
• In dialysis patients, a significant increase in hemoglobin was observed with iron supplementation when serum ferritin was <160 ng/mL, suggesting this might be a practical upper threshold for supplementation in this population 4
• Avoid iron overload by not chronically maintaining TSAT >50% or serum ferritin >800 ng/mL 1
• The goal of iron therapy is to improve erythropoiesis, not just to attain specific levels of TSAT and/or serum ferritin 1