What is the appropriate workup and management for a patient with iron deficiency anemia?

Iron Deficiency Anemia Workup

All patients with confirmed iron deficiency anemia require bidirectional endoscopy (upper endoscopy with duodenal biopsies and colonoscopy) except menstruating women, and should start oral iron supplementation immediately while the workup proceeds. 1

Diagnostic Confirmation

Establish the diagnosis using:

• Hemoglobin <13 g/dL in men or <12 g/dL in non-pregnant women 1
• Ferritin <45 ng/mL confirms iron deficiency in patients without inflammation 1
• In chronic inflammatory conditions (IBD, CKD, heart failure), use ferritin <100 ng/mL or transferrin saturation <20% 1, 2

Serum ferritin is the most powerful diagnostic test for iron deficiency, with <12 μg/dL being diagnostic, though it may be falsely elevated by inflammation, malignancy, or hepatic disease. 3

Initial History and Testing

Obtain specific details about:

• NSAID/aspirin use (stop if possible) 3, 1
• Menstrual blood loss patterns in premenopausal women 3
• Dietary iron intake adequacy 3
• Family history of GI malignancy or bleeding disorders 1

Perform these screening tests in all patients:

• Celiac disease serology (anti-endomysial or anti-tissue transglutaminase antibodies with IgA level to exclude IgA deficiency) 3, 1
• Helicobacter pylori testing (urea breath test or stool antigen) 1

Small bowel biopsies during endoscopy are mandatory as 2-3% of patients with iron deficiency anemia have celiac disease, even with normal-appearing mucosa. 3, 1

Gastrointestinal Evaluation Strategy

For patients >45 years old (men and postmenopausal women):

• Perform bidirectional endoscopy: upper endoscopy with duodenal biopsies AND colonoscopy 3, 1
• Upper endoscopy reveals a cause in 30-50% of patients 3
• Colonoscopy is mandatory even if upper endoscopy finds a lesion, as dual pathology occurs in 10-15% of patients 3
• Do not accept oesophagitis, erosions, or peptic ulcer as the sole cause without completing lower GI evaluation 3

For patients <45 years old:

• Only perform upper endoscopy with small bowel biopsy if upper GI symptoms are present 3
• All others should have celiac serology (with IgA level) 3
• Perform colonoscopy only if specific indications exist 3

For menstruating women:

• Investigation may be deferred if menorrhagia is documented and responds to iron therapy 3
• However, the 2024 AGA guideline supports bidirectional endoscopy in all men and postmenopausal women 1

Iron Replacement Therapy

Start oral iron immediately while workup proceeds:

• Ferrous sulfate 325 mg daily (65 mg elemental iron) or alternate-day dosing for better absorption 1, 4
• Alternative formulations: ferrous gluconate or ferrous fumarate are equally effective 3
• Ascorbic acid enhances absorption and should be added if response is poor 3
• Expect hemoglobin to rise by 2 g/dL after 3-4 weeks 3

Use intravenous iron for:

• Intolerance to at least two oral preparations 3
• Malabsorption (celiac disease, post-bariatric surgery) 3, 2
• Active inflammatory bowel disease with compromised absorption 3
• Ongoing blood loss unresponsive to oral iron 3
• Pregnancy (second/third trimester) 2
• Portal hypertensive gastropathy with ongoing bleeding 3

The rise in hemoglobin with IV iron is no quicker than oral preparations, but IV iron is indicated when oral therapy fails or is contraindicated. 3

Follow-Up and Monitoring

Reassess in 2-4 weeks to confirm response to oral iron. 1

Failure to respond (hemoglobin not rising by 2 g/dL in 3-4 weeks) indicates:

• Poor compliance 3
• Misdiagnosis 3
• Continued blood loss 3
• Malabsorption 3

Monitor hemoglobin and MCV every 3 months for 1 year, then annually. 1

Resolution of anemia should be achieved by 6 months in 80% of patients. 3

Special Populations

Inflammatory bowel disease:

• Determine if anemia is from inadequate intake/absorption or GI bleeding 3
• Treat active inflammation to enhance iron absorption 3
• Use IV iron if active inflammation with compromised absorption 3

Post-bariatric surgery:

• Use IV iron for iron deficiency anemia with no identifiable chronic GI blood loss, as duodenal absorption is disrupted 3

Portal hypertensive gastropathy:

• Start with oral iron initially 3
• Use IV iron if ongoing bleeding unresponsive to oral therapy 3
• Consider nonselective β-blockers to treat portal hypertension 3

Gastric antral vascular ectasia (GAVE):

• If inadequate response to iron replacement, perform endoscopic therapy with band ligation or argon plasma coagulation 3

Small-bowel angioectasias:

• Perform deep enteroscopy with distal attachment 3
• Treat with argon plasma coagulation or hemostatic clips 3
• Always accompany endoscopic treatment with iron replacement 3