What is the next step in managing a patient with severe iron deficiency anemia (IDA) and low iron saturation, whose hemoglobin and hematocrit have dropped despite iron supplementation?

Management of Severe Iron Deficiency Anemia with Inadequate Response to Oral Iron

Switch to intravenous iron immediately—this patient has severe absolute iron deficiency (TSAT 4%) with worsening anemia despite oral supplementation, indicating either malabsorption, ongoing blood loss, intolerance, or non-compliance. 1

Immediate Next Steps

1. Transition to Intravenous Iron Therapy

• Discontinue oral iron and initiate IV iron as the patient has demonstrated an inadequate response to oral supplementation 1
• A TSAT <20% has high sensitivity for diagnosing absolute or functional iron deficiency, and this patient's TSAT of 4% indicates severe depletion 1
• Preferred IV formulations include ferric carboxymaltose (up to 1,000 mg per week, 15-minute infusion) or iron isomaltoside (up to 1,000 mg, 15-minute infusion) for rapid repletion 1
• Hemoglobin should increase by 1-2 g/dL within 4-8 weeks of IV iron therapy 1

2. Investigate the Underlying Cause

Failure to respond to oral iron is usually due to poor compliance, misdiagnosis, continued blood loss, or malabsorption 1

Essential Diagnostic Workup:

• Bidirectional endoscopy (upper GI endoscopy with small bowel biopsies AND colonoscopy) is mandatory, as dual pathology occurs in 10-15% of patients 1
• Small bowel biopsies during upper endoscopy are critical—2-3% of IDA patients have celiac disease 1
• Do not accept superficial findings (esophagitis, erosions, peptic ulcer) as the sole cause until lower GI tract is examined 1
• Evaluate for ongoing blood loss sources: menorrhagia in premenopausal women, gastrointestinal bleeding, NSAID use 1

Additional Laboratory Assessment:

• Check ferritin (though less reliable with TSAT this low) 1
• Consider soluble transferrin receptor (sTfR) if inflammatory conditions are present, as it is more sensitive than ferritin in inflammation 1
• Reticulocyte hemoglobin content (CHr) or equivalent (RET-He) provides direct assessment of functional iron availability if available 1

3. Monitor Response and Adjust Treatment

• Hemoglobin should rise by 2 g/dL after 3-4 weeks of appropriate iron therapy 1
• If no response occurs, evaluate for:
  • Ongoing occult blood loss requiring more aggressive investigation 1
  • Alternative diagnoses (functional iron deficiency, anemia of chronic disease) 1
  • Need for transfusion if hemoglobin is critically low 1

IV Iron Dosing Specifics

For severe iron deficiency with TSAT of 4%:

• Ferric carboxymaltose: 15 mg/kg up to 1,000 mg IV, can repeat after 7 days for total cumulative dose of 1,500 mg 2
• Expected increases: ferritin rises by 200-260 ng/mL and TSAT increases by 13-20% within 35 days 2
• Monitor phosphate levels post-infusion as treatment-emergent hypophosphatemia can occur 1

Common Pitfalls to Avoid

• Do not continue oral iron indefinitely without response—this delays diagnosis and treatment of the underlying cause 1
• Do not skip lower GI evaluation even if upper endoscopy reveals a lesion, unless it's carcinoma or celiac disease 1
• Do not assume menstruation alone explains severe IDA with TSAT of 4%—this degree of deficiency warrants full investigation 1
• Most infusion reactions to IV iron are non-IgE-mediated (CARPA), not true allergies, and are self-limited 1

Follow-Up Strategy

• Recheck hemoglobin and iron parameters 4-8 weeks after IV iron initiation 1
• Once anemia corrects, continue iron supplementation for 3 months to replenish stores 1
• Monitor hemoglobin every 3 months for one year, then annually 1
• Patients with recurrent blood loss require more frequent and aggressive monitoring 1