What is the recommended diagnostic work‑up and management of iron‑deficiency anemia caused by occult gastrointestinal bleeding or heavy menstrual bleeding (menorrhagia)?

Management of Iron Deficiency Anemia from Occult GI Bleeding or Menorrhagia

All patients with iron deficiency anemia require bidirectional endoscopy (upper endoscopy with small bowel biopsies plus colonoscopy) regardless of whether menorrhagia or other bleeding source seems obvious, because dual pathology occurs in 10-15% of cases and serious GI lesions must be excluded. 1, 2

Diagnostic Work-Up Algorithm

Initial Laboratory Confirmation

• Ferritin <12 μg/L confirms iron deficiency, though levels <45 ng/mL (or <100 ng/mL with inflammation) are diagnostic in most contexts 3, 4
• Transferrin saturation <20% supports the diagnosis when ferritin is borderline 5
• MCV typically <80 fL in established iron deficiency, though normocytic anemia can occur early 5

Mandatory GI Investigation

Upper endoscopy should be performed first and reveals a cause in 30-50% of patients 1, 2:

• Obtain small bowel biopsies during every upper endoscopy even if mucosa appears normal, as 2-3% of iron deficiency anemia patients have celiac disease 1, 3, 2
• Do not accept minor lesions (esophagitis, erosions, aphthous ulcers, peptic ulcer) as the sole cause at this stage 1

Colonoscopy must follow even if upper endoscopy is positive (unless carcinoma or celiac disease is found), because 10-15% have dual pathology 1, 2:

• Colonoscopy is superior to barium enema for detecting angiodysplasia and allows tissue biopsy 1, 2
• Bidirectional endoscopy can be performed in the same session for efficiency 1

Additional Non-Invasive Testing

• Screen for celiac disease serologically (tissue transglutaminase antibody with IgA level) in all patients, as it accounts for 3-5% of cases 2
• Perform urinalysis to exclude urinary tract bleeding as a rare cause 2
• Test for Helicobacter pylori as it is a common treatable cause 4

Special Considerations for Pre-Menopausal Women

Even with documented menorrhagia, full GI investigation is still required if:

• The patient is over age 50 1
• There are any GI symptoms present 2
• Iron deficiency persists despite treating menorrhagia and providing iron supplementation 2

In younger women with clear menorrhagia and no GI symptoms, a reasonable initial approach is to treat the bleeding and provide iron supplementation, but proceed to endoscopy if anemia recurs or fails to correct 4:

• This exception applies only to women of reproductive age with documented heavy menstrual bleeding
• Any red flags (family history of GI cancer, weight loss, GI symptoms) mandate immediate endoscopy

Treatment Protocol

Iron Replacement

All patients should receive oral iron supplementation to correct anemia and replenish stores 1:

• Continue iron for 3 months after hemoglobin normalizes to replenish body stores 1
• Every-other-day dosing improves absorption and reduces side effects 4
• Evaluate response in 2-4 weeks; lack of response warrants intravenous iron or further investigation 4

When to Pursue Small Bowel Investigation

Further small bowel evaluation is indicated only if 1, 2:

• Anemia is transfusion-dependent
• There is inadequate response to iron replacement after treating identified causes
• Iron deficiency recurs despite correction
• Patient is under age 50 (to rule out small bowel neoplasm) 6

Capsule endoscopy is the preferred small bowel test when indicated, as it is highly sensitive for mucosal lesions 2:

• Enteroscopy may detect and treat small bowel angiodysplasia in transfusion-dependent cases 1
• Small bowel radiology is rarely useful unless Crohn's disease is suspected 1

Follow-Up Monitoring

Monitor hemoglobin and MCV at 3-month intervals for one year, then annually 1:

• Give additional oral iron if hemoglobin or MCV falls below normal
• Check ferritin in doubtful cases
• Further investigation is only necessary if hemoglobin and MCV cannot be maintained with iron supplementation 1

Critical Pitfalls to Avoid

• Never assume dietary deficiency or menorrhagia as the sole cause without GI investigation in appropriate patients, as this misses malignancies 5, 2
• Do not stop investigation after finding minor upper GI lesions—complete the lower GI evaluation 1, 2
• Mild anemia is not less significant than severe anemia as an indicator of serious disease 5
• Faecal occult blood testing has no role in diagnosis—it is insensitive and non-specific 1
• Discontinue NSAIDs and aspirin whenever possible, as they are major contributors to occult bleeding 3