What is the best treatment plan for a patient with severe iron deficiency anemia (hypoferritinemia, elevated TIBC, low transferrin saturation)?

Severe Iron Deficiency Anemia Treatment

Start oral ferrous sulfate 324 mg (65 mg elemental iron) three times daily immediately, and simultaneously investigate for gastrointestinal blood loss with upper endoscopy (including small bowel biopsies for celiac disease) and colonoscopy. 1

Interpretation of Your Labs

Your results confirm severe absolute iron deficiency anemia:

• Iron 23 μg/dL (normal 50-175): markedly low 1
• TIBC 268 μg/dL (normal 250-370): low-normal, but should be elevated in pure iron deficiency 1
• Transferrin saturation 9% (normal 20-50%): severely low, diagnostic of iron deficiency 1

The slightly low TIBC (rather than elevated as expected) suggests possible coexisting inflammation or chronic disease, but the severely low saturation confirms true iron deficiency requiring treatment. 1, 2

Immediate Treatment Protocol

Oral Iron Supplementation (First-Line)

• Ferrous sulfate 324 mg (65 mg elemental iron) three times daily 3
• Alternative formulations (ferrous gluconate, ferrous fumarate) are equally effective if tolerability is an issue 2
• Typical dosing range: 100-200 mg elemental iron daily in divided doses 1
• Recent evidence suggests alternate-day dosing may improve absorption with fewer side effects, though this is not yet standard practice 1

Expected Response

• Hemoglobin should rise by 2 g/dL after 3-4 weeks of adequate therapy 2
• Recheck hemoglobin at 4-8 weeks, not earlier 1, 2
• Do not recheck iron studies until 8-10 weeks after starting treatment, as ferritin levels are falsely elevated immediately after iron therapy 1

Mandatory Gastrointestinal Investigation

All patients with confirmed iron deficiency anemia require GI evaluation unless there is documented significant non-GI blood loss. 1

Upper Endoscopy (Do First)

• Reveals a cause in 30-50% of patients 1
• Obtain small bowel biopsies during endoscopy as 2-3% of iron deficiency anemia patients have celiac disease 1
• Look for: gastric cancer, NSAID-related ulcers, angiodysplasia, esophagitis 1

Lower Endoscopy (Colonoscopy)

• Required even if upper endoscopy reveals pathology (except carcinoma or celiac disease), as dual pathology occurs in ~10% of cases 1
• Look for: colon cancer, polyps, inflammatory bowel disease, angiodysplasia 1

Additional Considerations

• Stop NSAIDs and aspirin if possible before and during investigation 1
• Document dietary history, but do not assume dietary deficiency as the sole cause—full GI workup is still required 1
• Consider celiac serology (anti-endomysial antibody) if endoscopy cannot be performed 1

When to Use Intravenous Iron

Switch to IV iron if: 1

• Oral iron not tolerated (constipation, diarrhea, nausea are common) 1
• No therapeutic response after 4-8 weeks of oral therapy 1, 2
• Ongoing GI blood loss exceeds absorption capacity (e.g., angiodysplasia) 4
• Rapid replacement needed (e.g., before elective surgery) 1
• Malabsorption present (celiac disease, IBD, prior gastric/small bowel surgery) 1

IV Iron Formulations

• Ferric carboxymaltose is best studied: 1 gram infused over 15 minutes 1
• Iron sucrose and ferric gluconate require multiple administrations 1
• Avoid high molecular weight iron dextran (highest risk of serious reactions) 1
• Serious reactions are rare (<1:250,000) with modern formulations 1

Critical Pitfalls to Avoid

• Do not skip GI investigation even with obvious dietary deficiency—serious pathology may coexist 1
• Do not recheck ferritin early after starting iron therapy—it will be falsely elevated 1
• Do not give iron supplementation if ferritin >100 μg/L without clear indication—potentially harmful 1
• Do not assume prior GI surgery explains new iron deficiency—investigate for new pathology 1
• Do not use oral iron in heart failure patients—poorly absorbed and associated with side effects; use IV iron instead 1

Special Populations Requiring Modified Approach

Chronic Kidney Disease

• Different diagnostic thresholds: absolute iron deficiency defined as transferrin saturation ≤20% with ferritin ≤100 μg/L (predialysis) or ≤200 μg/L (hemodialysis) 1
• Coordinate with nephrology for management 1

Inflammatory Bowel Disease

• Ferritin up to 100 μg/L may still reflect iron deficiency in presence of inflammation 1
• Oral iron should contain ≤100 mg elemental iron daily in IBD 1
• IV iron indicated if Hb <100 g/L with moderate-to-severe anemia 1

Chronic Heart Failure

• IV iron has prognostic benefit even with functional iron deficiency (ferritin <100 μg/L or transferrin saturation <20%) 1
• Avoid oral iron—no prognostic benefit demonstrated 1