A patient with serum iron 187 µg/dL, total iron‑binding capacity 389 µg/dL, transferrin saturation 48 %, ferritin 29 ng/mL and a normal complete blood count—what is the most likely diagnosis and how should it be managed?

Diagnosis: Iron Deficiency Without Anemia

This patient has absolute iron deficiency without anemia, confirmed by a ferritin of 29 ng/mL (below the 30 ng/mL threshold) and transferrin saturation of 48% that appears paradoxically elevated but requires further investigation for underlying causes. 1

Understanding the Laboratory Pattern

Iron Deficiency Confirmation

• Ferritin 29 ng/mL definitively establishes iron deficiency in the absence of inflammation, as values <30 ng/mL confirm depleted iron stores when C-reactive protein is normal 2, 1
• The normal CBC indicates this is iron deficiency without anemia—a common early stage affecting up to 45% of at-risk populations before hemoglobin drops 2

The Paradoxical Transferrin Saturation

• A transferrin saturation of 48% is abnormally high and inconsistent with typical iron deficiency, where TSAT should be <16–20% 2, 1
• This discordant pattern (low ferritin + high TSAT) suggests either:
  • Recent iron ingestion or supplementation that transiently elevated serum iron 1
  • Hemolysis releasing iron from red cells 2
  • Laboratory error or timing issue, as serum iron shows marked day-to-day and diurnal variation 1
  • Early hereditary hemochromatosis (though ferritin would typically be elevated) 2

Mandatory Diagnostic Workup

Confirm Iron Status and Rule Out Confounders

• Measure C-reactive protein immediately to exclude inflammation that could falsely lower ferritin or affect iron parameters 1
• Repeat fasting morning iron studies (serum iron, TIBC, ferritin) after withholding any iron supplements for at least 48 hours to eliminate transient elevation 1
• Obtain reticulocyte count to assess for hemolysis, which would explain high serum iron with low ferritin 2

Identify the Source of Iron Loss

• In men and postmenopausal women, gastrointestinal evaluation is mandatory—upper and lower endoscopy to exclude malignancy or bleeding lesions 1
• In premenopausal women, assess menstrual blood loss: soaking through protection every 1–2 hours or periods >7 days indicate heavy bleeding 1
• Dietary history: quantify heme iron intake, as vegetarian/vegan diets provide poorly absorbed non-heme iron 1
• Medication review: NSAIDs, aspirin, and anticoagulants cause occult GI blood loss 1
• Screen for celiac disease with anti-endomysial or tissue transglutaminase antibodies, as 2–3% of iron deficiency cases are due to malabsorption 1
• Urinalysis to detect hematuria as a renal source of chronic blood loss 1

Management Strategy

First-Line Oral Iron Therapy

• Prescribe ferrous sulfate 325 mg (65 mg elemental iron) every other day on an empty stomach, as alternate-day dosing markedly improves absorption by avoiding hepcidin-mediated blockade 1
• Target ferritin ≥50 ng/mL and transferrin saturation ≥20% to ensure adequate repletion 1
• Reassess iron studies and CBC at 4–8 weeks; expect hemoglobin increase of 1–2 g/dL if anemia develops 1

Indications to Switch to Intravenous Iron

• Gastrointestinal intolerance (nausea, constipation, diarrhea) to oral iron 1
• No hematologic response after 4–8 weeks of adequate oral therapy 1
• Chronic kidney disease with eGFR <30 mL/min/1.73 m² 1
• Documented malabsorption (celiac disease, inflammatory bowel disease, post-bariatric surgery) 1
• Ongoing blood loss exceeding oral replacement capacity 1

Intravenous Iron Options

Formulation	Maximum Single Dose	Key Features
Ferric carboxymaltose	1,000 mg	Rapid infusion; low hypersensitivity risk [1]
Ferric derisomaltose	1,000 mg or 20 mg/kg (max 1,500 mg)	FDA-approved for total-dose infusion; reduces cardiovascular mortality in heart failure [1]
Iron sucrose	200 mg	No test dose required [1]
Low-molecular-weight iron dextran	High-dose infusion	Requires test dose due to anaphylaxis risk [1]

Critical Pitfalls to Avoid

• Do not dismiss iron deficiency based on the elevated TSAT alone—ferritin <30 ng/mL is definitive for depleted stores regardless of other parameters 1
• Do not attribute iron deficiency to diet or menstruation without comprehensive GI evaluation in adults, as occult malignancy must be excluded 1
• Do not measure iron studies within 4 weeks of IV iron infusion, as circulating iron falsely elevates results 1
• Do not continue oral iron indefinitely without reassessment—lack of response at 4–8 weeks mandates investigation for malabsorption or switch to IV iron 1
• Do not rely on MCV to exclude iron deficiency—more than 50% of iron-deficient patients have normal MCV 1