What is the appropriate workup and management for iron‑deficiency anemia presenting with low serum iron and low hemoglobin?

Workup and Management of Iron Deficiency Anemia

Begin oral iron replacement therapy immediately with one tablet daily of ferrous sulfate, fumarate, or gluconate while simultaneously pursuing diagnostic workup—do not delay treatment while awaiting investigations unless colonoscopy is imminent. 1

Diagnostic Confirmation

Serum ferritin is the single most useful marker for diagnosing iron deficiency anemia. 1 A ferritin <30 μg/L in the absence of inflammation confirms iron deficiency, though values <12 μg/L are diagnostic in all contexts. 1

Key diagnostic considerations:

• Ferritin can be falsely elevated in chronic inflammation, malignancy, or hepatic disease—if ferritin is 12-100 μg/L with suspected iron deficiency, measure transferrin saturation (TSAT). 1
• TSAT <20% supports iron deficiency even when ferritin is equivocal. 1, 2
• A hemoglobin rise ≥10 g/L within 2 weeks of iron therapy is highly suggestive of absolute iron deficiency, even if iron studies were equivocal. 1

Initial Workup

The minimum laboratory assessment includes: 1

• Complete blood count with red cell indices (MCV, MCH, RDW)
• Reticulocyte count
• Serum ferritin
• Transferrin saturation
• C-reactive protein (to identify inflammation that may elevate ferritin)

Take a detailed history focusing on: 1

• Dietary iron intake (vegetarian/vegan diets have lower bioavailable iron) 1
• Menstrual blood loss in premenopausal women 2
• NSAID or aspirin use 1
• Gastrointestinal symptoms (though often absent even with GI malignancy) 1

Mandatory Investigations

In men and postmenopausal women with newly diagnosed iron deficiency anemia, gastroscopy and colonoscopy should be first-line investigations to exclude gastrointestinal malignancy. 1 CT colonography is reasonable if colonoscopy is not suitable. 1

Screen for celiac disease in all patients with iron deficiency anemia—it is found in 3-5% of cases and can be diagnosed serologically or via small bowel biopsy at gastroscopy. 1

Perform urinalysis or urine microscopy to exclude renal tract bleeding. 1

Common Pitfall

Do not assume dietary insufficiency or menstruation as the sole cause without investigation—gastrointestinal pathology including cancer frequently coexists and must be excluded. 1

Treatment Approach

First-Line: Oral Iron

Start with ferrous sulfate, fumarate, or gluconate 325 mg once daily. 1 If not tolerated, reduce to one tablet every other day, which maintains efficacy while reducing gastrointestinal side effects. 1

• Take on an empty stomach for optimal absorption, though taking with food improves tolerance in some patients. 1
• Co-administer with 500 mg vitamin C to enhance absorption. 1
• Avoid tea and coffee around dosing times as they impair iron absorption. 1
• Monitor hemoglobin response within 4 weeks—expect rise of ≥10 g/L within 2 weeks if truly iron deficient. 1

Indications for Intravenous Iron

Consider intravenous iron for: 1, 2

• Oral iron intolerance or gastrointestinal side effects
• Malabsorption conditions (celiac disease, post-bariatric surgery, inflammatory bowel disease)
• Ongoing blood loss exceeding intestinal absorption capacity
• Chronic inflammatory conditions (chronic kidney disease, heart failure, inflammatory bowel disease, cancer)
• Second and third trimesters of pregnancy
• Inadequate response to oral iron after 4 weeks

Parenteral iron is not routinely indicated except in these specific circumstances—intravenous administration in athletes, for example, is only justified with pathologically impaired gut absorption. 1

Further Investigation for Refractory or Recurrent Cases

If bidirectional endoscopy is negative and iron deficiency anemia recurs or responds inadequately to iron replacement: 1

• Capsule endoscopy is the preferred test for small bowel examination—it is highly sensitive for mucosal lesions including angiodysplasia. 1
• CT/MR enterography is complementary for inflammatory and neoplastic small bowel disease. 1
• Investigate the renal tract if not already done. 1

After negative capsule endoscopy of acceptable quality, further GI investigation is only needed if iron deficiency anemia persists despite iron replacement. 1

Long-Term Management

Long-term iron replacement therapy is appropriate when the cause of recurrent iron deficiency anemia is unknown or irreversible (e.g., angiodysplasia, hereditary hemorrhagic telangiectasia). 1

Hemoglobin normalizes with iron replacement in most cases, but iron deficiency anemia recurs in a minority on long-term follow-up—these patients require ongoing monitoring and may need intermittent or continuous iron supplementation. 1, 3

Transfusion Considerations

Limited packed red cell transfusion may occasionally be required for symptomatic anemia with hemodynamic compromise, but iron replacement therapy is still necessary post-transfusion to replete stores. 1