With serum iron 51 µg/dL, total iron‑binding capacity 333 µg/dL, transferrin saturation 15 % and ferritin 33 ng/mL, what is the likely diagnosis and what is the appropriate initial treatment and work‑up?

Iron Deficiency Anemia: Diagnosis and Management

Your laboratory values confirm absolute iron deficiency anemia requiring immediate oral iron supplementation and mandatory investigation for the underlying cause of iron loss. 1

Diagnosis

Your iron panel demonstrates classic iron deficiency:

• Transferrin saturation of 15% falls below the diagnostic threshold of 16% for iron deficiency in adults 2
• Ferritin of 33 ng/mL confirms depleted iron stores, as values <100 ng/mL indicate absolute iron deficiency requiring treatment 1
• Elevated TIBC of 333 µg/dL reflects your body's compensatory attempt to maximize iron-binding capacity when stores are low 1
• Low serum iron of 51 µg/dL indicates insufficient circulating iron 2

The combination of low ferritin (<100 ng/mL) and low transferrin saturation (<16%) unequivocally confirms absolute iron deficiency with empty iron stores. 1

Immediate Treatment

Start oral iron supplementation immediately:

• Ferrous sulfate 325 mg tablets contain 65 mg elemental iron 1
• Ferrous gluconate 325 mg contains 38 mg elemental iron 1
• Ferrous fumarate 325 mg contains 106 mg elemental iron 1

Dosing strategy for optimal absorption:

• Administer on an empty stomach (≥1 hour before or ≥2 hours after meals) 1
• Use alternate-day dosing (every other day) rather than daily, as this markedly improves fractional absorption by avoiding hepcidin-mediated blockade 1
• Reduce elemental iron dose to 50–100 mg per administration; higher doses do not increase absorption and worsen gastrointestinal side effects 1

Expected response: Hemoglobin should increase by 1–2 g/dL within 4–8 weeks of adequate therapy 1, 3

Mandatory Work-Up for Underlying Cause

Iron deficiency rarely occurs without an identifiable source of loss or inadequate intake. 1

Essential investigations:

1. Gastrointestinal evaluation:

• Fecal occult blood testing to screen for GI bleeding 1
• In men and postmenopausal women, confirmed iron deficiency mandates upper and lower endoscopy to exclude malignancy 1
• Nine percent of patients older than 65 years with iron deficiency anemia have gastrointestinal cancer 3

2. Celiac disease screening:

• Serologic testing is essential, given 3–5% prevalence among patients with iron deficiency anemia 1

3. Complete blood count with differential:

• Evaluate for microcytosis, hypochromia, and abnormal white blood cell counts that may indicate myeloproliferative disorders 1

4. Renal function assessment:

• Urinalysis to detect hematuria or proteinuria as sources of chronic iron loss 1
• Estimated GFR to assess for chronic kidney disease, which contributes to both iron deficiency and anemia 1

5. Inflammatory markers:

• C-reactive protein to identify concurrent inflammation, as inflammation can falsely elevate ferritin and mask true iron deficiency 1

6. Additional considerations based on demographics:

• In premenopausal women: assess menstrual blood loss 1
• Evaluate for dietary insufficiency (restrictive diets, vegetarian/vegan) 1
• Screen for NSAID use, blood donation, or high-impact athletic activity causing hemolysis 1

Monitoring and Follow-Up

Reassess at 4 weeks:

• If hemoglobin has not increased by 1–2 g/dL, consider 1, 3:
  • Malabsorption of oral iron
  • Continued bleeding
  • Unidentified lesion
  • Need for intravenous iron

Repeat iron studies 4–8 weeks after completing oral iron course 2, 1

Treatment targets:

• Ferritin ≥50 ng/mL (in absence of inflammation) or ≥100 ng/mL to ensure sufficient stores 2, 1
• Transferrin saturation ≥20% to confirm adequate iron for erythropoiesis 2, 1

When to Switch to Intravenous Iron

Consider IV iron if 2, 1:

• Gastrointestinal intolerance to oral iron (nausea, constipation, diarrhea)
• Lack of hematologic response after 4–8 weeks of adequate oral therapy
• Chronic kidney disease with eGFR <30 mL/min/1.73 m²
• Documented malabsorption (celiac disease, inflammatory bowel disease, post-bariatric surgery)
• Ongoing blood loss exceeding oral replacement capacity

Among early non-responders to oral iron, only 21% achieve improvement with continued oral therapy, whereas 65% respond when switched to intravenous iron. 1

Available IV formulations:

• Ferric carboxymaltose: up to 1,000 mg per infusion 2, 1
• Ferric derisomaltose: up to 1,500 mg (only FDA-approved total-dose infusion; shown to reduce cardiovascular mortality in heart failure) 2, 1
• Iron sucrose: up to 200 mg per infusion 2, 1

Critical Pitfalls to Avoid

• Do not rely on "normal" serum iron to exclude deficiency; serum iron shows high day-to-day variability and is affected by meals, diurnal changes, and inflammation 2, 1
• Do not delay GI evaluation in men and postmenopausal women when iron deficiency is identified 1, 3
• Do not continue oral iron indefinitely without reassessment; lack of response after 4–8 weeks warrants evaluation for malabsorption or transition to IV iron 1
• Do not measure iron parameters within 4 weeks of IV iron infusion, as circulating iron falsely elevates results 2, 1
• Do not use proton-pump inhibitors or H₂-blockers during oral iron therapy, as they significantly impair absorption 1