What is the recommended diagnostic workup and treatment approach for a patient suspected of having iron deficiency anemia?

Iron Deficiency Anemia: Diagnostic Workup and Treatment

Diagnostic Criteria

Diagnose iron deficiency anemia when hemoglobin is <13 g/dL in men or <12 g/dL in non-pregnant women AND ferritin is <45 ng/mL. 1

• Use a ferritin cut-off of <45 ng/mL rather than the older threshold of <15 ng/mL, as this provides superior sensitivity and specificity for detecting iron deficiency 2, 1
• For pregnant women, the hemoglobin threshold is <11 g/dL 1
• In patients with chronic inflammation or chronic kidney disease, additional laboratory tests including transferrin saturation (<20%) may be needed since ferritin can be falsely elevated as an acute phase reactant 2, 3

Identifying the Underlying Cause

Initial Non-Invasive Testing

Screen all patients for celiac disease with serology (transglutaminase antibody IgA and total IgA) before proceeding to endoscopy. 2, 1

• Test for H. pylori non-invasively in patients with suspected infection, followed by treatment if positive 2, 1
• Small bowel biopsy is only indicated if celiac serology is positive 2
• Do NOT perform fecal occult blood testing—it provides no diagnostic benefit in iron deficiency anemia workup 1

Endoscopic Evaluation

For postmenopausal women and men: Perform bidirectional endoscopy (both upper endoscopy and colonoscopy) immediately. 2, 1

• This is a strong recommendation with moderate quality evidence 2
• The risk of gastrointestinal malignancy justifies the small procedural risk 2

For premenopausal women: Perform bidirectional endoscopy, though this is a conditional recommendation. 2, 1

• Premenopausal women <40 years with obvious menstrual blood loss as the cause may reasonably defer endoscopy initially 1, 4
• However, if symptoms persist despite iron replacement or if there are red flags (weight loss, abdominal pain, elevated CRP), proceed with endoscopy 4

After Negative Bidirectional Endoscopy

Do NOT routinely perform video capsule endoscopy or small bowel imaging after negative bidirectional endoscopy. 2

• Reserve small bowel investigation (capsule endoscopy, CT/MRI enterography) for patients with red flags suggesting small bowel pathology: involuntary weight loss, persistent abdominal pain, elevated inflammatory markers, or failure to respond to iron therapy 4
• Exercise caution in patients on anticoagulation or antiplatelet therapy where identifying small bowel lesions would alter management 2

Treatment Approach

First-Line: Oral Iron Therapy

Initiate oral iron supplementation immediately upon diagnosis with a target of 100-200 mg elemental iron daily, regardless of pending investigations. 1, 3

• Ferrous sulfate 325 mg daily (containing 65 mg elemental iron) or alternate-day dosing reduces side effects while maintaining efficacy 3
• Treatment duration typically requires 3-6 months to normalize hemoglobin and replenish iron stores 4
• Monitor response to therapy; failure to improve warrants further investigation 1

Indications for Intravenous Iron

Use intravenous iron for patients with:

• Oral iron intolerance or gastrointestinal side effects 1, 3
• Malabsorption conditions (celiac disease, atrophic gastritis, post-bariatric surgery) 1, 3
• Active inflammatory bowel disease with compromised absorption 1, 3
• Chronic kidney disease or heart failure 3
• Ongoing blood loss exceeding intestinal absorption capacity 5
• Second and third trimesters of pregnancy 3

Blood Transfusions

Reserve blood transfusions exclusively for patients with cardiovascular instability or at imminent risk due to severe anemia. 1

• Transfusions do not address the underlying iron deficiency and should not be used for routine management 1

Disease-Specific Considerations

Celiac Disease

• Ensure strict adherence to a gluten-free diet to improve iron absorption 1
• Use oral iron based on severity and tolerance; switch to intravenous iron if stores fail to improve 1

Inflammatory Bowel Disease

• Treat active inflammation to enhance iron absorption 1
• Prefer intravenous iron when active inflammation compromises absorption 1

Gastric Antral Vascular Ectasia

• Consider endoscopic therapy if inadequate response to iron replacement 1

Common Pitfalls to Avoid

• Do not use routine gastric biopsies to diagnose atrophic body gastritis—this is not recommended 2
• Do not delay iron replacement while awaiting diagnostic workup; start treatment immediately 1
• Do not assume menstrual bleeding is the sole cause in premenopausal women without evaluating for other pathology if symptoms persist 2
• Do not continue oral iron indefinitely without monitoring response; failure to respond indicates need for further evaluation or switch to intravenous therapy 1, 4