How is iron deficiency managed in gastrointestinal (GI) disorders?

Iron Metabolism and Management in Gastrointestinal Disorders

Start with oral ferrous sulfate 200 mg once daily (not three times daily) as first-line therapy while simultaneously investigating the underlying GI cause, and switch to intravenous iron if oral therapy fails after trial of two different formulations or in patients with severe malabsorption. 1

Diagnostic Workup

All adults with iron deficiency anemia require bidirectional GI endoscopy to identify underlying pathology, as approximately one-third of men and postmenopausal women have pathological abnormalities, most commonly GI malignancies. 2 The investigation should proceed urgently and not be delayed while treating with iron. 2

Key Diagnostic Steps:

• Use ferritin <45 mg/dL as the diagnostic threshold for iron deficiency in non-inflammatory conditions. 1
• In inflammatory GI conditions (IBD, celiac disease), iron deficiency may exist with ferritin 45-100 mg/dL—confirm with transferrin saturation, soluble transferrin receptor, or reticulocyte hemoglobin. 1
• Screen for celiac disease via serology or small bowel biopsy, as it accounts for 3-5% of IDA cases. 2
• Evaluate for H. pylori infection, which impairs iron absorption. 1
• Exclude urinary blood loss with urinalysis. 2
• Avoid fecal occult blood testing—it is insensitive and non-specific with no clinical utility. 1, 2

Oral Iron Therapy

Optimal Dosing Strategy:

Take iron once daily, not multiple times per day. Hepcidin levels rise within hours of iron ingestion and remain elevated for 48 hours, blocking further absorption and increasing side effects without improving efficacy. 1

• Ferrous sulfate is the gold standard: Start with ferrous sulfate, ferrous fumarate, or ferrous gluconate—all equally effective and least expensive. 1, 3, 4
• Take on an empty stomach when possible for optimal absorption; if not tolerated, take with meals (preferably with meat protein). 1
• Add 500 mg vitamin C to enhance absorption, especially if taking with food containing calcium or fiber. 1
• Avoid tea and coffee within one hour of iron intake—they are powerful inhibitors of absorption. 1

Expected Response:

• Hemoglobin should rise by 2 g/dL after 3-4 weeks. 1, 2
• Continue therapy for 3 months after anemia correction to replenish iron stores. 1, 2
• Failure to respond indicates: poor compliance, continued blood loss, malabsorption, or misdiagnosis. 1, 2

Common Side Effects:

Constipation (12%), diarrhea (8%), and nausea (11%) are common with oral iron. 1 These side effects are dose-dependent and can be reduced with once-daily dosing. 1

Intravenous Iron Therapy

Use IV iron as first-line therapy in patients with severe malabsorption (IBD, celiac disease, post-gastrectomy) or as second-line after failure of two different oral iron formulations. 1, 5

Indications for IV Iron:

• Intolerance to at least two oral iron preparations 1, 2
• Inflammatory bowel disease: IV iron is preferred because oral iron may worsen disease activity and is insufficient to overcome chronic blood loss. 5
• Severe iron deficiency requiring rapid repletion (e.g., pre-operative patients) 4
• Conditions with impaired absorption: celiac disease, post-gastrectomy, chronic kidney disease 6, 5

IV Iron Formulations:

• Ferric carboxymaltose (Injectafer): 750 mg per dose, up to 1,500 mg total (two doses separated by ≥7 days). 6
• Ferric derisomaltose: 500-1,000 mg in single infusion. 4
• Serious hypersensitivity reactions are rare (approximately 1:200,000), but IV iron must be administered in medical facilities by trained providers. 1, 4
• Monitor phosphate levels: ferric carboxymaltose carries increased risk of hypophosphatemia. 4

Management in Specific GI Conditions

Inflammatory Bowel Disease:

• Prefer IV iron over oral iron due to better tolerance, faster repletion, and avoidance of potential disease exacerbation. 5
• Oral iron side effects may mimic IBD flares, complicating disease management. 5

Celiac Disease:

• Screen all IDA patients as celiac disease is found in 3-5% of cases. 2
• IV iron may be necessary until gluten-free diet restores intestinal absorption. 5

Angioectasias/Vascular Malformations:

• Endoscopic treatment should be accompanied by iron replacement. 1
• Medical therapy is reserved for refractory cases when iron replacement and endoscopic therapy fail. 1

Monitoring and Follow-Up

• Check hemoglobin and MCV every 3 months for the first year, then annually. 1, 2
• Restart iron if hemoglobin or MCV falls below normal; check ferritin in doubtful cases. 1, 2
• Further investigation is only necessary if hemoglobin cannot be maintained with iron supplementation. 1, 2

Critical Pitfalls to Avoid

• Never assume the cause without investigation—even obvious sources (menorrhagia) may coexist with occult GI malignancy. 2
• Do not prescribe iron three times daily—once daily dosing is equally effective with fewer side effects due to hepcidin regulation. 1
• Do not delay endoscopy while treating empirically—investigation must proceed urgently in at-risk populations. 2
• Do not use parenteral iron as first-line unless specific indications exist—it is expensive and carries rare but serious risks. 1
• Multidisciplinary involvement with gastroenterology, hematology, and nutrition is often needed in complex cases. 1