What serum ferritin, transferrin saturation, and hemoglobin thresholds indicate that oral iron therapy should be continued?

Thresholds for Continuing Oral Iron Therapy

Continue oral iron supplementation when ferritin remains <100 ng/mL, transferrin saturation <20%, or hemoglobin has not yet normalized, provided the patient tolerates therapy and shows evidence of response. 1

Iron Status Targets During Treatment

Ferritin Thresholds

• Maintain ferritin >100 ng/mL during erythropoietin therapy or active treatment of iron deficiency anemia 1
• Post-treatment ferritin levels >400 μg/L prevent recurrence of iron deficiency for 1-5 years better than lower levels 1
• In chronic kidney disease patients, target ferritin >200 ng/mL to minimize erythropoiesis-stimulating agent requirements 2

Transferrin Saturation Targets

• Continue oral iron until transferrin saturation exceeds 20% 1
• Values below 20% indicate inadequate iron availability for erythropoiesis even when ferritin is normal 1, 3
• In inflammatory states, transferrin saturation may be more reliable than ferritin for assessing true iron status 3

Hemoglobin Response

• Expect hemoglobin to rise by 1-2 g/dL within 4 weeks if oral iron is working 2, 4
• If no hemoglobin increase occurs after 4 weeks, oral iron is likely failing due to malabsorption, ongoing blood loss, or functional iron deficiency requiring intravenous iron 2, 4
• Only 21% of patients who fail to respond in the first 2 weeks will eventually respond to continued oral therapy 2

When to Stop Oral Iron

Discontinuation Criteria

• Stop oral iron when hemoglobin normalizes AND ferritin exceeds 100 ng/mL AND transferrin saturation exceeds 20% 1
• Continue oral iron for 3 months after hemoglobin correction to fully replenish iron stores 2
• In IBD patients specifically, no more than 100 mg elemental iron per day should be used 1

Failure of Oral Iron

• Switch to intravenous iron if hemoglobin fails to increase after 8-12 weeks of appropriate oral therapy 2, 4
• Approximately 65% of oral iron non-responders will respond to intravenous iron 2
• Oral iron absorption becomes limited when ferritin exceeds ~200 ng/mL or transferrin saturation exceeds 20% in non-erythropoietin-treated patients 1

Special Populations Requiring Different Thresholds

Inflammatory Bowel Disease

• Use oral iron only in patients with mild anemia (hemoglobin 11.0-12.9 g/dL in men, 11.0-11.9 g/dL in women), clinically inactive disease, and no prior intolerance 1
• Prefer intravenous iron when hemoglobin <10 g/dL, disease is clinically active, or prior oral iron intolerance exists 1

Chronic Kidney Disease on Hemodialysis

• Oral iron is inadequate for most hemodialysis patients receiving erythropoietin 1
• Blood losses from hemodialysis exceed oral iron absorption capacity even at 200 mg elemental iron daily 1
• Maintain ferritin >100 ng/mL and transferrin saturation >20% with intravenous iron 1, 3

Cancer Patients

• Absolute iron deficiency (ferritin <30 ng/mL and transferrin saturation <15%) warrants oral or intravenous iron 1
• Functional iron deficiency (ferritin <800 ng/mL and transferrin saturation <20%) may benefit from intravenous iron supplementation during erythropoiesis-stimulating agent therapy 1

Monitoring Schedule

During Active Treatment

• Recheck hemoglobin, ferritin, and transferrin saturation after 8-10 weeks of oral iron therapy 2, 5
• If hemoglobin has not increased by 1-2 g/dL at 4 weeks, reassess for malabsorption, ongoing blood loss, or need for intravenous iron 2, 4

Maintenance Phase

• For patients with recurrent iron deficiency, repeat iron studies every 6-12 months 5
• In hemodialysis patients on maintenance intravenous iron, reassess iron status every 3 months 2

Common Pitfalls to Avoid

• Do not continue oral iron indefinitely without monitoring response—failure to increase hemoglobin by 4 weeks indicates treatment failure 2, 4
• Do not rely solely on ferritin in inflammatory conditions—ferritin is an acute-phase reactant and may be falsely elevated while true iron deficiency persists 1, 3
• Do not use oral iron in hemodialysis patients expecting adequate response—blood losses exceed absorption capacity in most cases 1
• Avoid iron supplementation when ferritin >800 ng/mL and transferrin saturation >50% to prevent iron overload 1