Should I treat a patient with low ferritin (iron storage) but normal Transferrin Saturation (TSAT)?

Treatment of Low Ferritin with Normal TSAT

Patients with low ferritin but normal transferrin saturation (TSAT) should receive iron supplementation, particularly if they have symptoms of iron deficiency or are at risk for developing iron deficiency anemia.

Understanding Iron Parameters and Discordant Results

• Ferritin reflects iron storage, while TSAT reflects iron that is readily available for erythropoiesis 1
• Discordant results (low ferritin with normal TSAT) can occur and represent a diagnostic challenge 1
• This pattern may indicate early or developing iron deficiency where stores are depleted but circulating iron remains adequate for immediate needs 1

Diagnostic Considerations

• Traditional definition of absolute iron deficiency includes:
  • Serum ferritin <100 ng/mL in chronic kidney disease (CKD) patients 1, 2
  • Serum ferritin <50 ng/mL in otherwise healthy individuals 3
  • TSAT <20% is generally considered indicative of iron deficiency 1
• When TSAT and ferritin values diverge, they become less reliable in guiding iron therapy 4
• In non-CKD patients, a ferritin cut-off of 30 µg/L is appropriate for healthy adults >15 years 3

Treatment Approach

For CKD Patients:

• Iron supplementation is recommended when ferritin is <100 ng/mL regardless of TSAT 1
• The goal is to maintain ferritin ≥100 ng/mL and TSAT ≥20% 1
• Intravenous (IV) iron is preferred for patients on dialysis, while either IV or oral iron is recommended for non-dialysis CKD patients 2

For Non-CKD Patients:

• Oral iron therapy is the first-line treatment when ferritin is low, even with normal TSAT 3
• Use preparations with reasonable elemental iron content (28-50 mg) to minimize gastrointestinal side effects 3
• Consider enhancers of iron absorption (vitamin C, heme iron sources) and avoid inhibitors (tea, coffee, calcium) 3

Monitoring Response

• Repeat basic blood tests (hemoglobin, ferritin, TSAT) after 8-10 weeks of treatment 1
• If no response occurs after adequate iron supplementation, consider other causes of low ferritin 1
• Patients with repeatedly low ferritin will benefit from intermittent oral supplementation to preserve iron stores 3

Special Considerations

• Low TSAT with low ferritin is associated with worse physical health-related quality of life in CKD patients, even after accounting for hemoglobin levels 5
• In heart failure patients, TSAT <20% appears to be a more reliable indicator of iron deficiency than ferritin alone 6
• Avoid iron supplementation when ferritin is normal or high unless TSAT is low, as unnecessary iron can be harmful 3

Common Pitfalls

• Relying solely on ferritin or TSAT can lead to misdiagnosis 4
• Measuring iron parameters within 4 weeks of IV iron administration can give misleading results 1
• Inflammation can elevate ferritin as an acute phase reactant, potentially masking iron deficiency 1
• Long-term daily oral or IV iron supplementation in the presence of normal or high ferritin is not recommended and potentially harmful 3