What is the recommended treatment for iron deficiency anemia, including oral and intravenous iron regimens and management of underlying causes?

Treatment of Iron Deficiency Anemia

Start with oral ferrous sulfate 200 mg twice daily for most patients, continuing for 3 months after correction to replenish stores, but switch to intravenous iron for malabsorption conditions, intolerance to oral therapy, or chronic inflammatory diseases where oral iron is ineffective. 1

First-Line Oral Iron Therapy

Standard Regimen

• Ferrous sulfate 200 mg twice daily is the simplest and most cost-effective initial treatment 1
• Lower doses may be equally effective and better tolerated—consider dose reduction if patients experience side effects 1
• Alternative formulations include ferrous fumarate, ferrous gluconate, or iron suspensions if ferrous sulfate is not tolerated 1
• Continue oral iron for 3 months after anemia correction to fully replenish iron stores 1

Optimizing Oral Absorption

• Take iron on an empty stomach for maximum absorption, though some patients tolerate it better with meals 2
• Add vitamin C 500 mg with each dose to enhance absorption, particularly when calcium or fiber is present 2
• Taking iron with meat protein improves absorption 2
• Avoid tea and coffee within one hour of iron administration as they powerfully inhibit absorption 2
• Dose once daily only—hepcidin levels remain elevated for 48 hours after oral iron, blocking further absorption and increasing side effects without benefit 2

Expected Response

• Hemoglobin should rise by 2 g/dL after 3-4 weeks of treatment 1
• Hemoglobin should increase by 1 g/dL within 2 weeks of appropriate supplementation 2
• Ferritin should increase within one month in adherent patients 2
• Failure to achieve these targets indicates poor compliance, misdiagnosis, continued blood loss, malabsorption, or need to switch to intravenous iron 1, 2

Intravenous Iron Therapy

Clear Indications for IV Iron

• Intolerance to at least two oral iron preparations 1
• Malabsorption conditions: celiac disease (after failed gluten-free diet adherence), inflammatory bowel disease with active inflammation, post-bariatric surgery (especially procedures bypassing duodenum/proximal jejunum) 1, 2
• H. pylori infection interfering with iron absorption (treat infection concurrently) 2
• Chronic inflammatory conditions: chronic kidney disease, chronic heart failure (ferritin <100 μg/L or transferrin saturation <20%), inflammatory bowel disease 1, 2
• Ongoing blood loss 3
• Pregnancy during second and third trimesters 4
• Failure of oral iron therapy: no hemoglobin increase by 1 g/dL within 2 weeks or ferritin failure to increase within one month in adherent patients 2

IV Iron Preparations (2011 British Society of Gastroenterology Data)

• Iron dextran (Cosmofer): 20 mg/kg maximum single dose, 6-hour infusion, can replenish iron in single infusion but carries 0.6-0.7% serious reaction risk with reported fatalities 1
• Iron sucrose (Venofer): 200 mg maximum single dose, 10-minute bolus infusion (more convenient than 2-hour infusion) 1
• Ferric carboxymaltose (Ferinject): 1000 mg maximum single dose, 15-minute infusion, similar side effect rates (22-29%) but no anaphylaxis reported at time of guideline publication 1
• Formulations allowing 1-2 infusions to replace total iron deficit are preferred due to similar efficacy and safety profiles 2

Managing IV Iron Reactions

• Mild infusion reactions: stop infusion, restart 15 minutes later at slower rate 2
• Major reactions are rare and represent complement activation-related pseudo-allergy rather than true allergy 2
• Avoid diphenhydramine—its side effects can be mistaken for worsening reactions; use corticosteroids for severe reactions instead 2
• Resuscitation facilities must be available during infusion 1

Disease-Specific Management

Inflammatory Bowel Disease

• Oral iron should contain no more than 100 mg elemental iron daily 1
• Intravenous iron is indicated for moderate to severe anemia (Hb <100 g/L) or intolerance to oral iron 1
• Ferritin up to 100 μg/L may still reflect iron deficiency in presence of inflammation—check transferrin saturation 1
• Optimize disease control to bring IBD into remission, which improves iron absorption and response to therapy 1
• Monitor for recurrent iron deficiency every 3 months for at least one year after correction 1

Chronic Heart Failure

• Screen with ferritin and transferrin saturation 1
• Iron deficiency defined as ferritin <100 μg/L and/or transferrin saturation <20% 1
• Use intravenous iron—it has demonstrated prognostic benefit in meta-analyses 1
• Avoid oral iron in CHF—poorly absorbed due to gut edema, frequently causes side effects, and shows no prognostic benefit 1
• Consider endoscopic evaluation if absolute iron deficiency present, in consultation with cardiology team 1

Post-Bariatric Surgery

• Use intravenous iron initially rather than attempting oral supplementation, particularly for procedures bypassing duodenum and proximal jejunum 1, 2
• History of GI or bariatric surgery should not preclude searching for other causes of new IDA 1

Chronic Kidney Disease

• Intravenous iron required if oral iron not tolerated, ineffective, or if dialysis commenced 1
• Erythropoietin may also be needed—manage in conjunction with nephrology team 1

H. pylori Infection

• Test for H. pylori by non-invasive testing if IDA persists or recurs after normal endoscopy, and eradicate if present 1
• H. pylori urease (CLO) testing of gastroscopy biopsy specimens is an alternative approach 1
• Eradication appears to reverse anemia based on small studies and case reports 1

Critical Management Principles

Identify and Treat Underlying Cause

• Treatment of underlying cause prevents further iron loss, but all patients still require iron supplementation to correct anemia and replenish stores 1
• Treating iron deficiency alone without addressing root cause results in continued therapeutic failure 2
• All men and postmenopausal women with IDA require bidirectional GI endoscopy to exclude malignancy 3
• Premenopausal women over age 45 should be investigated according to full guidelines; those under 45 with upper GI symptoms need endoscopy and small bowel biopsy 1

Monitoring and Follow-Up

• Once normal, monitor hemoglobin and red cell indices every 3 months for one year, then after another year 1
• Give additional oral iron if hemoglobin or MCV falls below normal (check ferritin in doubtful cases) 1
• Further investigation only necessary if hemoglobin and MCV cannot be maintained with supplementation 1
• If treatment goals not achieved, consider further evaluation for missed diagnosis or ongoing blood loss 1

Common Pitfalls to Avoid

• Do not use faecal occult blood testing in IDA investigation—it is insensitive and non-specific 1
• Do not continue oral iron indefinitely without monitoring response 1
• Do not assume menstrual bleeding is the sole cause in premenopausal women over 45 without appropriate investigation 1
• Do not use intramuscular iron dextran as first choice—it is painful and requires multiple injections 1
• Ascorbic acid 250-500 mg twice daily may enhance absorption, but no data confirm effectiveness specifically for IDA treatment 1