What is the interpretation of lab results showing severe iron deficiency anemia in a 63-year-old male with hemoglobin (Hgb) of 12.8, mean corpuscular hemoglobin concentration (MCHC) of 31.3, unsaturated iron-binding capacity (UIBC) of 378, iron level of 19, iron saturation of 5, ferritin of 10, and transferrin of 320, who has been taking iron supplements daily?

Interpretation: Severe Absolute Iron Deficiency Despite Daily Oral Iron Supplementation

This 63-year-old male has severe absolute iron deficiency with inadequate response to oral iron therapy, requiring immediate investigation for ongoing blood loss (particularly gastrointestinal malignancy) and transition to intravenous iron replacement. 1, 2

Laboratory Analysis

The iron panel demonstrates classic absolute iron deficiency:

• Ferritin 10 ng/mL: Severely depleted iron stores (normal >30 ng/mL in men without inflammation) 1, 2
• Transferrin saturation 5%: Critically low (normal >20%), indicating insufficient iron available for erythropoiesis 1
• Serum iron 19 mcg/dL: Markedly reduced 1
• UIBC 378 mcg/dL and transferrin 320 mg/dL: Both elevated, reflecting the body's attempt to capture more iron 1
• Hemoglobin 12.8 g/dL: Mild anemia (normal >13 g/dL in men) 2
• MCHC 31.3 g/dL: Low-normal, suggesting early hypochromia 1

This constellation confirms absolute iron deficiency, not functional iron deficiency or anemia of chronic disease, as ferritin <30 ng/mL is highly specific for depleted iron stores even in inflammatory states. 1

Critical Clinical Concern: Failure of Oral Iron Therapy

The persistence of severe iron deficiency despite daily oral iron supplementation is a red flag requiring urgent investigation. 2, 3 This indicates either:

1. Ongoing Blood Loss (Most Likely)

• Gastrointestinal malignancy must be excluded: In men over 50 with iron deficiency anemia, approximately 9% have gastrointestinal cancer 3
• Immediate endoscopic evaluation is indicated: Begin with colonoscopy given age >50, followed by upper endoscopy if colonoscopy is negative 3
• Other GI sources: peptic ulcer disease, angiodysplasia, inflammatory bowel disease 2

2. Malabsorption of Oral Iron

• Atrophic gastritis, celiac disease, Helicobacter pylori infection 2
• Post-bariatric surgery anatomy 2
• Concurrent use of proton pump inhibitors or H2-blockers (impairs iron absorption) 1
• Inflammatory conditions causing hepcidin upregulation 1

3. Non-compliance or Inadequate Dosing

• Verify actual intake and dosing regimen 1

Immediate Management Algorithm

Step 1: Urgent Gastrointestinal Evaluation

• Colonoscopy first (age >50 with iron deficiency anemia) 3
• Upper endoscopy if colonoscopy negative 3
• Fecal occult blood testing has limited utility when iron deficiency is already confirmed 1

Step 2: Assess for Malabsorption

• Celiac serologies (tissue transglutaminase IgA with total IgA) 2
• Review medication list for PPI/H2-blocker use 1
• Consider Helicobacter pylori testing 2

Step 3: Switch to Intravenous Iron

Intravenous iron is indicated for this patient given failure of oral therapy and need for rapid repletion. 1, 2 Indications include:

• Oral iron intolerance or non-response 2
• Ongoing blood loss 2
• Malabsorption conditions 2
• Need for rapid correction 1

Available IV iron preparations: 1

• Low molecular weight iron dextran (requires test dose due to anaphylaxis risk)
• Iron sucrose
• Ferric carboxymaltose (can give >1000 mg per infusion)
• Ferumoxytol
• Iron isomaltoside

Dosing strategy: Total iron deficit can be calculated, typically requiring 1000-1500 mg total dose for this degree of deficiency. 1

Step 4: Discontinue or Modify Oral Iron

• If switching to IV iron, oral iron can be discontinued 1
• If continuing oral iron while awaiting IV therapy, consider alternate-day dosing (better absorption due to lower hepcidin response) 1

Follow-Up Monitoring

Recheck iron studies and hemoglobin in 4-6 weeks after initiating IV iron: 1, 2

• Expected hemoglobin increase: 1-2 g/dL per month with adequate iron repletion 3
• Target ferritin: >100 ng/mL 1
• Target transferrin saturation: >20% 1

If no response to IV iron: Consider bone marrow biopsy to evaluate for other causes of anemia or inflammatory iron block. 1, 3

Common Pitfalls to Avoid

• Do not assume oral iron failure is due to non-compliance alone in a 63-year-old male—always investigate for GI malignancy 3
• Do not rely on hemoglobin alone: This patient has only mild anemia but severe iron deficiency, which can cause significant symptoms (fatigue, exercise intolerance, restless legs) even before frank anemia develops 4, 2
• Do not continue oral iron indefinitely without response: After 60-90 days of oral iron without improvement, switch to IV iron or investigate further 5
• Do not overlook inflammatory conditions: While ferritin <30 ng/mL indicates absolute deficiency, concurrent inflammation could be contributing; check CRP if clinical suspicion exists 1