What is the recommended diagnostic workup and management for iron deficiency anemia in adults?

Iron Deficiency in Adults: Diagnostic Workup and Management

Diagnostic Confirmation

Serum ferritin is the single most useful test for diagnosing iron deficiency, with ferritin <15 μg/L being diagnostic of absent iron stores and <30 μg/L indicating low body iron stores. 1, 2

Laboratory Evaluation

• Ferritin interpretation:

  • <15 μg/L: Highly specific for iron deficiency (specificity 0.99) 1
  • <30 μg/L: Generally indicates low iron stores 1, 2
  • <45 μg/L: Optimal cutoff balancing sensitivity and specificity (0.92), particularly useful when inflammation is present 1
  • <100 μg/L: May still indicate iron deficiency in inflammatory states 2

  • 150 μg/L: Unlikely to represent absolute iron deficiency even with inflammation 1

• Additional iron studies when ferritin is equivocal:

  • Transferrin saturation <20-30% supports iron deficiency diagnosis 2, 3
  • Mean corpuscular hemoglobin (MCH) may be more reliable than MCV as it's less affected by storage conditions and detects both absolute and functional iron deficiency 1
  • Mean corpuscular volume (MCV) <100 fL with low ferritin confirms iron deficiency anemia 3

• Functional diagnostic test:

  • A hemoglobin rise ≥10 g/L within 2 weeks of iron therapy is highly suggestive of absolute iron deficiency, even when iron studies are equivocal 1, 2

Anemia Definition

• Hemoglobin <130 g/L in men, <120 g/L in non-pregnant women, <110 g/L in pregnant women (2nd/3rd trimester) 2
• Investigation should be considered at any level of anemia when iron deficiency is present, though more severe anemia warrants more urgent evaluation 1

Initial Workup to Identify Underlying Cause

All adults with newly diagnosed iron deficiency anemia require investigation to identify the underlying cause, as approximately one-third of men and postmenopausal women have underlying pathological abnormalities, most commonly gastrointestinal. 1

Mandatory Initial Investigations

• Detailed history focusing on:

  • Menstrual blood loss patterns 4
  • Gastrointestinal symptoms or bleeding 4
  • Dietary intake and absorption issues 4
  • NSAID use 4
  • Prior gastric or bariatric surgery 4

• Urinalysis or urine microscopy to exclude renal tract blood loss 1, 2

• Coeliac disease screening (serological testing or small bowel biopsy at gastroscopy), as it accounts for 3-5% of iron deficiency anemia cases 1, 2

Endoscopic Evaluation

In men and postmenopausal women with newly diagnosed iron deficiency anemia, bidirectional endoscopy (gastroscopy and colonoscopy) should be the first-line gastrointestinal investigation. 1, 2

• CT colonography is a reasonable alternative for patients unsuitable for colonoscopy 1
• Hemoglobin electrophoresis should be performed in patients with microcytosis and normal iron studies, particularly in appropriate ethnic backgrounds, to exclude thalassemia before proceeding with gastrointestinal investigation 1

When to Investigate Premenopausal Women

• Gastrointestinal investigation generally not warranted in premenopausal women with non-anemic iron deficiency without other concerning features 1
• However, investigation should be considered if there are gastrointestinal symptoms, inadequate response to iron therapy, or recurrent iron deficiency anemia 1

Management of Iron Deficiency Anemia

Timing of Iron Replacement

Iron replacement therapy should not be deferred while awaiting investigations unless colonoscopy is imminent. 1

First-Line Oral Iron Therapy

Initial treatment should be one tablet daily of ferrous sulfate, fumarate, or gluconate (typically 325 mg ferrous sulfate daily or on alternate days). 1, 4

• If not tolerated, reduce to one tablet every other day 1
• Alternative oral preparations or parenteral iron should be considered if oral iron is not tolerated 1
• Monitor hemoglobin response within the first 4 weeks 1

Indications for Intravenous Iron

Intravenous iron is indicated for:

• Oral iron intolerance 4
• Poor absorption (celiac disease, post-bariatric surgery, atrophic gastritis) 4, 5
• Chronic inflammatory conditions (chronic kidney disease, heart failure, inflammatory bowel disease, cancer) 4, 5
• Ongoing blood loss 4
• Second and third trimesters of pregnancy 4

Further Investigation for Persistent or Recurrent Iron Deficiency Anemia

In patients with negative bidirectional endoscopy of acceptable quality who have either inadequate response to iron replacement therapy or recurrent iron deficiency anemia, further investigation of the small bowel and renal tract is recommended. 1

Small Bowel Evaluation

Capsule endoscopy is the preferred test for examining the small bowel because it is highly sensitive for mucosal lesions. 1, 2

• CT/MR enterography are complementary investigations for inflammatory and neoplastic small bowel disease 1, 2
• After negative capsule endoscopy of acceptable quality, further gastrointestinal investigation is only needed if ongoing iron deficiency anemia persists after iron replacement therapy 1

Long-Term Management

• Long-term iron replacement therapy is appropriate when the cause of recurrent iron deficiency anemia is unknown or irreversible 1
• Hemoglobin levels normalize with iron replacement in most cases, but iron deficiency anemia recurs in a minority on long-term follow-up 1

Common Pitfalls

• Ferritin is an acute phase protein: Apparently normal ferritin levels may occur with iron deficiency in inflammatory conditions; use the 45 μg/L cutoff in these contexts 1
• Don't miss thalassemia: MCV typically reduced out of proportion to anemia level; check hemoglobin electrophoresis before extensive gastrointestinal workup 1
• Limited transfusion role: Packed red cell transfusion may occasionally be required for symptomatic iron deficiency anemia, but iron replacement therapy is still necessary post-transfusion 1