Given iron studies showing total iron‑binding capacity 409 µg/dL, unsaturated iron‑binding capacity 355 µg/dL, serum iron 54 µg/dL, and iron saturation 13 %, what is the most likely diagnosis and what are the appropriate next steps in management?

Iron Deficiency with Depleted Iron Stores

Your patient has absolute iron deficiency with depleted iron stores, confirmed by a transferrin saturation of 13% (below the diagnostic threshold of 16%) and an elevated TIBC of 409 µg/dL. 1

Diagnostic Interpretation

Your iron panel demonstrates the classic pattern of iron deficiency:

• Transferrin saturation 13% is below the diagnostic cutoff of 16% for iron deficiency in adults, confirming true deficiency 1
• Elevated TIBC (409 µg/dL) reflects the body's compensatory attempt to maximize iron-binding capacity when iron stores are depleted 1
• Elevated UIBC (355 µg/dL) indicates a high proportion of vacant iron-binding sites on transferrin, which is a more accurate marker for empty iron stores than serum iron alone (diagnostic accuracy 0.80-0.97) 1
• Low serum iron (54 µg/dL) combined with these findings confirms absolute iron deficiency 1

The mathematical relationship confirms internal consistency: TIBC = serum iron + UIBC (409 = 54 + 355) 1

Mandatory Next Steps

1. Complete the Iron Panel

Obtain serum ferritin immediately to quantify iron stores and guide treatment targets 1:

• In the absence of inflammation (verify with C-reactive protein), ferritin <30 µg/L definitively establishes iron deficiency 1
• Ferritin <100 ng/mL confirms absolute iron deficiency requiring treatment 1
• Critical caveat: Ferritin is an acute-phase reactant and can be falsely elevated during illness, inflammation, or stress, potentially masking iron deficiency 1

Obtain complete blood count with hemoglobin, hematocrit, MCV, and reticulocyte count to assess the severity of anemia and bone marrow response 1

Measure C-reactive protein to assess for inflammation, which affects interpretation of ferritin levels 2, 1

2. Identify the Underlying Cause

Iron deficiency mandates a search for the underlying source, as it rarely occurs without identifiable loss or inadequate intake 1:

• Screen for gastrointestinal bleeding with fecal occult blood testing; if positive, endoscopic evaluation (colonoscopy first if age >50) is required 1, 3
• Assess menstrual blood loss in premenopausal women as a primary cause 1
• Evaluate for malabsorption disorders including celiac disease and inflammatory bowel disease 1
• Review medications for NSAID use, which commonly causes occult GI bleeding 1
• Consider dietary insufficiency, restrictive diets, blood donation, or high-impact athletic activity causing hemolysis 1

Calculate estimated glomerular filtration rate using age, gender, race, and serum creatinine to assess for chronic kidney disease (CKD stages 2-3), as CKD alters iron metabolism and treatment approach 1

3. Treatment Strategy

Initiate oral iron supplementation as first-line therapy unless contraindications exist 1:

• Therapeutic targets: Achieve ferritin ≥100 ng/mL and transferrin saturation ≥20% 1
• Reassess hemoglobin at 4 weeks: Expect a 1-2 g/dL increase if treatment is effective 3
• If no response after 4-8 weeks, consider malabsorption, continued bleeding, or switch to intravenous iron 1

Consider intravenous iron in specific circumstances 1:

• Gastrointestinal intolerance to oral iron
• CKD with eGFR <30 mL/min/1.73 m²
• Lack of hematologic response after adequate oral iron trial

Common Pitfalls to Avoid

• Do not dismiss iron deficiency based on "normal" serum iron alone, as serum iron exhibits high day-to-day variability and is influenced by recent meals, diurnal changes, and inflammation 1
• Do not assume normal ferritin excludes iron deficiency if inflammation is present; use the higher threshold of 100 µg/L in inflammatory states 2, 1
• Do not overlook gastrointestinal malignancy: 9% of patients older than 65 years with iron deficiency anemia have GI cancer when evaluated 3
• Do not stop at treating the anemia—failure to identify the underlying cause (especially occult bleeding) can lead to serious missed diagnoses 1, 3