What is the best approach to investigate microcytic anemia in a 42-year-old female with no reported rectal bleeding?

Investigation and Management of Microcytic Anemia in a 42-Year-Old Female

This patient requires immediate confirmation of iron deficiency with serum ferritin testing, followed by comprehensive gastrointestinal investigation regardless of symptoms, as iron deficiency anemia in adults is presumed to be from GI blood loss until proven otherwise. 1

Initial Diagnostic Workup

Confirm iron deficiency immediately:

• Order serum ferritin as the single most useful diagnostic test - ferritin <15 μg/L confirms absent iron stores, <30 μg/L indicates low body iron stores, and <45 μg/L provides optimal sensitivity and specificity for iron deficiency 2, 3
• Add transferrin saturation (TSAT <30% supports iron deficiency) and evaluate RDW (>14.0% with low MCV suggests iron deficiency rather than thalassemia) 2, 3
• The combination of MCV 64 fL with elevated RDW strongly indicates iron deficiency anemia rather than thalassemia trait 2

Critical point: Even though she denies rectal bleeding, the absence of visible bleeding does NOT exclude GI pathology - occult bleeding is common and faecal occult blood testing is insensitive and non-specific, so do not rely on it 1

Gastrointestinal Investigation Protocol

All patients with confirmed iron deficiency anemia require full GI evaluation unless there is documented significant non-GI blood loss: 1

Upper GI endoscopy first (expected to reveal cause in 30-50% of cases):

• Obtain small bowel biopsies during endoscopy to screen for celiac disease, as 2-3% of patients with iron deficiency anemia have celiac disease 1
• Do NOT accept findings of esophagitis, erosions, or peptic ulcer as the sole cause at this stage 1

Lower GI tract examination is mandatory even if upper endoscopy reveals pathology:

• Proceed with colonoscopy or double contrast barium enema, as dual pathology (lesions in both upper and lower GI tracts) occurs in 10-15% of patients 1
• Bidirectional endoscopy (same-session upper and lower) is an efficient approach 1

Rationale: At age 42, this patient is at risk for GI malignancy, and the severity of anemia (Hgb 74 g/L, MCV 64 fL) indicates significant chronic blood loss that must be explained 1, 4

Additional History to Obtain

• Menstrual history: Heavy menstrual bleeding is the most common cause in premenopausal women, but does NOT exclude concurrent GI pathology 2
• Medication use: Document aspirin, NSAIDs, and anticoagulants - stop NSAIDs if possible, but their use should not deter investigation 1
• Dietary assessment: Borderline deficient diets are common but should NOT be presumed as the sole cause - full GI investigation is still required 1
• Family history: Screen for thalassemia, sideroblastic anemia, telangiectasia, and bleeding disorders 1

Immediate Treatment While Investigating

Start oral iron supplementation immediately:

• Ferrous sulfate 200 mg three times daily - this is first-line therapy 1, 2
• Continue for at least three months after correction of anemia to replenish iron stores 1
• Expect hemoglobin rise ≥10 g/L within 2 weeks if iron deficiency is the cause - this confirms the diagnosis 2, 3

If no response to oral iron within 2-4 weeks, consider:

• Non-compliance, ongoing blood loss, malabsorption, or rare genetic disorders 2
• Intravenous iron if malabsorption is present (expect Hgb increase ≥2 g/dL within 4 weeks) 2, 5

Follow-Up Monitoring

Once hemoglobin normalizes:

• Monitor hemoglobin concentration and red cell indices at three-monthly intervals for one year, then after a further year 1, 2
• Provide additional oral iron if hemoglobin or MCV falls below normal 1, 2
• Further investigation is only necessary if hemoglobin and MCV cannot be maintained with iron supplementation 1

Critical Pitfalls to Avoid

• Do NOT assume dietary insufficiency or menstrual bleeding explains the anemia without completing GI investigation - iron deficiency in adults requires explanation of blood loss source 1, 2
• Do NOT accept upper GI findings alone as the cause - always complete lower GI evaluation due to 10-15% dual pathology rate 1
• Do NOT rely on faecal occult blood testing - it is insensitive and non-specific 1
• Do NOT stop investigation if patient denies symptoms - GI malignancy can present with iron deficiency anemia alone 1, 4

When to Consider Alternative Diagnoses

If ferritin is normal or elevated despite microcytosis:

• Consider anemia of chronic disease (low iron with decreased total iron-binding capacity) 6, 7
• Order hemoglobin electrophoresis if MCV is disproportionately low relative to degree of anemia or if patient has appropriate ethnic background 2, 6
• Consider rare genetic disorders if extreme microcytosis (MCV <70), family history, or failure to respond to iron therapy 2, 5