What are the clinical treatment guidelines for iron deficiency anemia?

Clinical Treatment Guidelines for Iron Deficiency Anemia

First-Line Treatment: Oral Iron Supplementation

Start with ferrous sulfate 200 mg once daily, which is the preferred first-line treatment due to its effectiveness, low cost, and superior tolerability compared to multiple daily dosing. 1, 2

Optimal Oral Iron Regimen

• Ferrous sulfate 200 mg once daily is the standard formulation, taken as a single morning dose rather than divided throughout the day 1, 2
• Alternate-day dosing (120 mg every other day) may optimize absorption and reduce side effects in women with mild iron deficiency anemia, as daily doses ≥60 mg stimulate hepcidin elevation that persists 24 hours and blocks subsequent iron absorption 3
• Add vitamin C (ascorbic acid) 500 mg with each iron dose to enhance absorption, particularly when response is suboptimal 1, 2
• Alternative ferrous salts (ferrous gluconate, ferrous fumarate) are equally effective if ferrous sulfate is not tolerated 1, 2
• Take on an empty stomach for optimal absorption, though taking with food is acceptable if gastrointestinal side effects occur 2

Expected Response and Duration

• Hemoglobin should rise by approximately 2 g/dL after 3-4 weeks of treatment 1, 2
• Continue oral iron therapy for 3 months after anemia correction to fully replenish iron stores 1, 2
• If no hemoglobin rise occurs within 4 weeks, assess for non-adherence, ongoing blood loss, or malabsorption 1, 2

Monitoring Schedule

• Check hemoglobin and red cell indices at 3-month intervals for the first year, then again after another year 2
• Provide additional iron supplementation if hemoglobin or MCV falls below normal 2

When to Switch to Intravenous Iron

Intravenous iron should be used as first-line treatment in specific clinical scenarios where oral iron is inadequate or contraindicated. 1

Absolute Indications for IV Iron

• Inflammatory bowel disease with active inflammation and hemoglobin <10 g/dL (100 g/L) 1
• Intolerance to at least two different oral iron preparations 1, 2
• Post-bariatric surgery patients with disrupted duodenal iron absorption 1, 2
• Inadequate response to oral iron after 4 weeks of appropriate therapy 1, 2
• Ongoing gastrointestinal blood loss exceeding oral replacement capacity 2, 4

Relative Indications for IV Iron

• Celiac disease with inadequate response to oral iron despite strict gluten-free diet adherence 1, 2
• Portal hypertensive gastropathy with ongoing bleeding not responding to oral therapy 1, 2
• Patients requiring erythropoiesis-stimulating agents 1

IV Iron Formulation Selection

• Prefer IV iron formulations that can replace iron deficits with 1-2 infusions rather than those requiring multiple infusions 1, 2
• All IV iron formulations have similar safety profiles; true anaphylaxis is very rare 1
• Most reactions are complement activation-related pseudo-allergy (infusion reactions) rather than true anaphylaxis 1

Special Population Considerations

Inflammatory Bowel Disease

• Treat active inflammation first to enhance iron absorption and reduce iron depletion 1, 2
• Use IV iron as first-line in patients with clinically active IBD, hemoglobin <10 g/dL, or previous oral iron intolerance 1
• Oral iron may be used in patients with mild anemia whose disease is clinically inactive 1
• Re-treat with IV iron when serum ferritin drops below 100 μg/L or hemoglobin falls below 12 g/dL (women) or 13 g/dL (men) 1

Celiac Disease

• Ensure strict adherence to gluten-free diet to improve iron absorption 1, 2
• Start with oral iron supplementation based on severity of deficiency and patient tolerance 1
• Progress to IV iron if oral supplementation fails despite dietary compliance 1, 2
• Screen for celiac disease with antiendomysial antibody and IgA measurement in patients with unexplained iron deficiency 2, 5

Portal Hypertensive Gastropathy

• Start with oral iron supplements initially to replenish iron stores 1, 2
• Switch to IV iron in patients with ongoing bleeding who do not respond to oral therapy 1, 2
• Consider nonselective β-blockers to treat portal hypertension when no other source of chronic blood loss is identified 1

Gastric Antral Vascular Ectasia (GAVE)

• Consider endoscopic therapy with endoscopic band ligation or argon plasma coagulation in patients with inadequate response to iron replacement 1

Post-Bariatric Surgery

• IV iron is preferred due to disrupted duodenal absorption mechanisms 1, 2

Diagnostic Workup for Unexplained Iron Deficiency Anemia

Investigation Strategy

• Perform bidirectional endoscopy (gastroscopy and colonoscopy) in men and postmenopausal women with unexplained iron deficiency anemia 5
• Conduct celiac disease screening with transglutaminase antibody (IgA type) and IgA measurement 2, 5
• Bidirectional endoscopy is not required in premenopausal women <40-45 years without upper gastrointestinal symptoms 1, 5
• Small intestine investigation (capsule endoscopy, CT/MRI enterography) should be conducted if red flags are present after negative bidirectional endoscopy, such as involuntary weight loss, abdominal pain, or elevated CRP 5

Age-Based Approach

• Patients >45 years should be investigated with bidirectional endoscopy due to increasing incidence of significant pathology with age 1
• Patients <45 years should have endoscopy only if upper GI symptoms are present, otherwise perform antiendomysial antibody testing to exclude celiac disease 1

Common Pitfalls to Avoid

• Do not prescribe multiple daily doses of oral iron – once-daily or alternate-day dosing improves tolerability with similar or better efficacy 2, 3
• Do not stop iron therapy when hemoglobin normalizes – continue for 3 months to replenish stores 1, 2
• Do not continue oral iron indefinitely without response – reassess after 4 weeks and switch to IV iron if hemoglobin fails to rise 2
• Do not overlook vitamin C supplementation when oral iron response is suboptimal 1, 2
• Do not fail to identify and treat the underlying cause of iron deficiency while supplementing 2
• Do not give afternoon or evening iron doses after a morning dose – circadian hepcidin increase is augmented by morning iron, blocking subsequent absorption 3

Failure to Respond to Treatment

Reassessment at 6 Months

• If anemia does not resolve within 6 months despite appropriate iron therapy, reassess for:

  • Ongoing blood loss 2, 5
  • Malabsorption syndromes 1, 2
  • Non-adherence to therapy 1, 2
  • Misdiagnosis 1

• Consider further gastrointestinal investigation with small bowel evaluation 2, 5

• Consider hematology consultation for complex cases 2

Audit Targets

• 90% of patients (excluding menstruating women) should have both upper GI endoscopy with small bowel biopsy and colonoscopy unless a firm cause is found with the first investigation 1
• Resolution of anemia should be achieved by 6 months in 80% of patients 1
• 90% of non-responders should be considered for further investigation 1