At what percent transferrin saturation should iron therapy be started?

When to Start Iron Therapy Based on Transferrin Saturation

Iron therapy should be initiated when transferrin saturation (TSAT) is less than 20%, particularly when accompanied by ferritin levels below 100 ng/mL. 1

Understanding Iron Status Assessment

Iron status evaluation relies on two primary markers:

• Transferrin Saturation (TSAT): Reflects iron readily available for erythropoiesis

  • Normal range: 20-50%
  • TSAT < 20% indicates iron deficiency for erythropoiesis
  • TSAT > 50% may indicate iron overload

• Serum Ferritin: Reflects iron storage

  • < 100 ng/mL in CKD patients indicates absolute iron deficiency
  • Can be elevated in inflammatory conditions despite iron deficiency

Iron Deficiency Classifications

1. Absolute Iron Deficiency:

   • TSAT < 20% AND ferritin < 100 ng/mL in CKD patients
   • TSAT < 20% AND ferritin < 30 ng/mL in cancer patients 1
   • Indicates depleted iron stores

2. Functional Iron Deficiency:

   • TSAT < 20% WITH normal or elevated ferritin (100-800 ng/mL)
   • Indicates adequate iron stores but impaired mobilization
   • Common during erythropoiesis-stimulating agent (ESA) therapy

Evidence-Based Recommendations

For CKD Patients:

• Start iron therapy when TSAT < 20% AND ferritin < 100 ng/mL 1
• Target maintenance of TSAT ≥ 20% and ferritin ≥ 100 ng/mL 1
• Consider iron therapy even with ferritin 100-800 ng/mL if TSAT remains < 20% 1

For Cancer Patients:

• Start iron therapy when TSAT < 20% regardless of ferritin level 1
• Higher threshold for absolute iron deficiency (ferritin < 100 ng/mL) due to inflammatory effects 1

For General Population:

• Start iron therapy when TSAT < 20% AND ferritin < 30 ng/mL 2

Clinical Considerations

• Inflammatory Conditions: Ferritin is an acute phase reactant and may be elevated despite iron deficiency
• ESA Therapy: Patients receiving ESAs have increased iron requirements and may need iron supplementation at higher ferritin levels
• Diurnal Variation: TSAT values fluctuate throughout the day; consistent timing of measurements is important 3

Route of Administration

• Oral Iron: First-line for most patients with absolute iron deficiency
• IV Iron: Consider for:
  • Patients with functional iron deficiency
  • Those with poor oral absorption
  • Hemodialysis patients
  • Patients with inflammatory conditions
  • Those with ongoing blood loss

Clinical Pitfalls to Avoid

1. Relying solely on ferritin: Inflammatory states can elevate ferritin despite iron deficiency
2. Ignoring TSAT when ferritin is normal/high: Functional iron deficiency requires treatment despite normal/high ferritin
3. Overtreatment: Excessive iron can cause oxidative stress; stop IV iron if ferritin > 800 ng/mL and TSAT > 50% 1
4. Undertreatment: Inadequate iron leads to ESA resistance and persistent anemia

Monitoring Response

• Measure hemoglobin, TSAT, and ferritin regularly
• Expect hemoglobin increase of 4-10 g/L following iron supplementation in deficient patients 1
• Consider alternative markers (reticulocyte hemoglobin content, percentage of hypochromic red cells) when standard markers are inconclusive 4

Recent research suggests that maintaining TSAT ≥ 20% with ferritin < 90 ng/mL may be optimal for hemoglobin response in hemodialysis patients 5, indicating that lower iron stores than previously recommended may be beneficial when iron availability is adequate.