Patient with hemoglobin 9.5 g/dL, serum iron 18 µg/dL, transferrin saturation 5.9 %, total iron‑binding capacity 304 µg/dL—what is the diagnosis and recommended management?

Iron Deficiency Anemia: Diagnosis and Management

This patient has absolute iron deficiency anemia requiring immediate oral iron supplementation, with intravenous iron reserved for non-response or intolerance.

Diagnostic Interpretation

Your laboratory values unequivocally confirm absolute iron deficiency anemia:

• Hemoglobin 9.5 g/dL indicates moderate anemia requiring treatment 1
• Transferrin saturation 5.9% is markedly below the diagnostic threshold of <16% for iron deficiency in adults, confirming iron-deficient erythropoiesis 1, 2
• Serum iron 18 µg/dL is severely depleted 1
• TIBC 304 µg/dL is elevated, reflecting the body's compensatory attempt to capture any available circulating iron when stores are empty 1, 2

The combination of low serum iron, elevated TIBC, and TSAT <16% definitively establishes absolute iron deficiency 1. This pattern indicates depleted iron stores with the bone marrow lacking sufficient available iron for hemoglobin synthesis 1.

Essential Additional Laboratory Testing

Before initiating treatment, obtain:

• Serum ferritin to quantify iron stores; expect <30 ng/mL in the absence of inflammation or <100 ng/mL if inflammation is present 1, 2
• C-reactive protein (CRP) to identify concurrent inflammation that may falsely elevate ferritin and guide interpretation 1
• Complete blood count with MCV and reticulocyte count to assess microcytosis and bone marrow response capacity 1
• Renal function (serum creatinine, eGFR) because chronic kidney disease alters iron metabolism and influences treatment choice 1, 2

Mandatory Investigation of Underlying Cause

Iron deficiency rarely occurs without an identifiable source of loss or inadequate intake 2. You must investigate the etiology:

In Men and Postmenopausal Women:

• Gastrointestinal evaluation is mandatory to exclude malignancy as a source of chronic blood loss 1
• Perform upper and lower endoscopy (esophagogastroduodenoscopy and colonoscopy) 2
• Test stool for occult blood 2
• Screen for celiac disease (tissue transglutaminase antibodies), which has 3–5% prevalence among patients with iron-deficiency anemia 2

In Premenopausal Women:

• Assess menstrual blood loss patterns (heavy or prolonged menses) 2
• If menstrual losses do not explain the severity, proceed with gastrointestinal evaluation 1

Additional Considerations:

• Dietary insufficiency (restrictive diets, vegetarian/vegan without supplementation) 2
• Malabsorption disorders (inflammatory bowel disease, post-bariatric surgery) 2
• NSAID use causing occult GI bleeding 2
• Frequent blood donation 2
• High-impact athletic activity causing intravascular hemolysis 2

First-Line Treatment: Oral Iron Supplementation

Initiate oral iron therapy immediately unless contraindications exist 2:

Dosing:

• Ferrous sulfate 325 mg (65 mg elemental iron) once daily 2
• Alternative formulations: ferrous gluconate 325 mg (38 mg elemental iron) or ferrous fumarate 325 mg (106 mg elemental iron) 2
• Administer on an empty stomach (≥1 hour before or ≥2 hours after meals) to maximize absorption 2

Optimizing Absorption:

• Alternate-day dosing (every other day) markedly improves fractional iron absorption by avoiding hepcidin-mediated blockade sustained by daily dosing 2
• Reduce elemental iron dose to 50–100 mg per administration; higher doses do not increase absorption and worsen gastrointestinal side effects 2

Expected Response:

• Hemoglobin should increase by 1–2 g/dL within 4–8 weeks of adequate therapy 2
• Reticulocytosis occurs at 3–5 days after iron administration, indicating bone marrow response 1

Common Side Effects:

• Constipation, diarrhea, nausea, and abdominal discomfort 1
• If intolerable, switch to alternate-day dosing or consider intravenous iron 2

Indications for Intravenous Iron

Switch to intravenous iron if any of the following apply 1, 2:

1. Gastrointestinal intolerance to oral iron despite alternate-day dosing 1, 2
2. Lack of hematologic response after 4–8 weeks of adequate oral therapy (persistent TSAT <20% or hemoglobin increase <1 g/dL) 1, 2
3. Chronic kidney disease with eGFR <30 mL/min/1.73 m² 1, 2
4. Documented malabsorption (celiac disease, inflammatory bowel disease, post-bariatric surgery) 2
5. Ongoing blood loss that exceeds the replacement capacity of oral iron 2
6. Chronic inflammatory conditions (heart failure, active IBD, cancer) where hepcidin blocks intestinal iron absorption 1, 2

Intravenous Iron Formulations:

Formulation	Maximum Single Dose	Special Considerations
Ferric carboxymaltose	1,000 mg	Rapid administration; low hypersensitivity risk; FDA-approved for IDA [3]
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]
Ferric derisomaltose	1,000 mg or 20 mg/kg (max 1,500 mg)	Only FDA-approved for total-dose infusion [2]

Ferric carboxymaltose is preferred for its convenience (up to 1,000 mg in a single 15-minute infusion) and proven efficacy in clinical trials 3. In the CONFIRM-HF trial, ferric carboxymaltose improved 6-minute walk distance by 25 meters versus placebo in heart failure patients with iron deficiency 3.

Treatment Targets After Iron Repletion

Aim for the following goals 1, 2:

• Transferrin saturation ≥20% to ensure adequate iron availability for erythropoiesis 1, 2
• Ferritin ≥50–100 ng/mL (in the absence of inflammation) to confirm sufficient iron stores 1, 2
• Hemoglobin normalization (≥12 g/dL in women, ≥13 g/dL in men) 4

Monitoring Schedule

• Do not repeat iron studies within 4 weeks of an IV iron infusion because circulating iron interferes with assay accuracy and ferritin may be falsely elevated 1, 2
• Optimal timing for reassessment is 4–8 weeks after the last IV iron dose or after completing an oral iron course 1, 2
• If no hematologic response occurs after 4–8 weeks of oral iron, switch to intravenous iron 2

Common Diagnostic and Treatment Pitfalls

1. Do not rely on "normal" serum iron to exclude iron deficiency. Serum iron exhibits high day-to-day variability, diurnal fluctuations, and post-prandial changes; ferritin and TSAT are far more reliable 1, 2

2. Do not dismiss iron deficiency based on ferritin alone in inflammatory states. Ferritin is an acute-phase reactant; in chronic inflammation, ferritin up to 100–300 ng/mL may still indicate true iron deficiency 1

3. Do not continue oral iron indefinitely without reassessment. Lack of response after 4–8 weeks warrants evaluation for malabsorption, ongoing blood loss, or transition to IV iron 2

4. Do not measure iron parameters too early after IV iron (within 4 weeks), as this yields falsely elevated results 1, 2

5. Oral iron is ineffective in functional iron deficiency with active inflammation because hepcidin blocks intestinal absorption; IV iron is required 1, 2

6. Do not delay gastrointestinal evaluation in men and postmenopausal women. Iron deficiency in these populations mandates exclusion of malignancy 1, 2

Special Considerations

If Chronic Kidney Disease Is Present:

• Absolute iron deficiency in CKD is defined as TSAT ≤20% with ferritin ≤100 µg/L (predialysis/peritoneal dialysis) or ≤200 µg/L (hemodialysis) 1
• IV iron is preferred over oral iron in CKD patients with eGFR <30 mL/min/1.73 m² 1, 2
• Coordinate with nephrology for management decisions and potential erythropoiesis-stimulating agent (ESA) therapy 1

If Chronic Inflammatory Conditions Are Present:

• In heart failure (NYHA class II–III), IV iron is indicated when ferritin <100 ng/mL or ferritin 100–300 ng/mL with TSAT <20% 1
• IV iron improves functional status and quality of life in heart failure patients with iron deficiency 1, 3
• In inflammatory bowel disease with active inflammation, IV iron bypasses hepcidin-mediated blockade of intestinal absorption 1