What is the management plan for a patient with microcytic anemia, indicated by low Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), and Mean Corpuscular Hemoglobin Concentration (MCHC)?

Management of Microcytic Anemia with Low MCV, MCH, and MCHC

Start oral iron supplementation with ferrous sulfate 200 mg three times daily immediately while simultaneously investigating the underlying cause of iron deficiency. 1, 2

Initial Diagnostic Workup

The most critical first step is confirming iron deficiency as the etiology:

• Check serum ferritin as the single most specific test for iron deficiency, with a cut-off of 45 μg/L providing optimal sensitivity and specificity in practice 1, 3
  • Ferritin <15 μg/L indicates absent iron stores
  • Ferritin <30 μg/L indicates low body iron stores 1
• Evaluate transferrin saturation (TSAT) as it is more sensitive than hemoglobin alone for detecting iron deficiency 1, 3
• Assess the RDW (red cell distribution width) to differentiate causes:
  • Low MCV with RDW >14.0% strongly suggests iron deficiency anemia
  • Low MCV with RDW ≤14.0% suggests thalassemia minor 1, 3

Common pitfall: Ferritin can be falsely elevated by inflammation, so add transferrin saturation if clinical suspicion for iron deficiency remains high despite normal ferritin 1

Investigate the Source of Iron Loss

In adults with confirmed iron deficiency, you must identify the source of blood loss:

• For men and non-menstruating women: Assume gastrointestinal blood loss until proven otherwise 1, 2
  • Order stool guaiac test for occult blood 2
  • Men with Hb <110 g/L or non-menstruating women with Hb <100 g/L warrant fast-track GI referral for endoscopy 1
• For premenopausal women: Obtain detailed menstrual history, as heavy menstrual bleeding is the most common cause 1, 2
• Assess dietary intake for inadequate iron consumption 2
• Screen for celiac disease if malabsorption is suspected 1

Treatment Protocol

First-Line Oral Iron Therapy

• Ferrous sulfate 200 mg (65 mg elemental iron) three times daily taken separately from meals 1, 2, 4
• Continue for at least 3 months after hemoglobin normalizes to replenish iron stores—stopping when hemoglobin normalizes leads to relapse 1, 2
• Alternative formulations if ferrous sulfate not tolerated: ferrous gluconate or ferrous fumarate 1, 3
• Add ascorbic acid (vitamin C) to enhance iron absorption 1, 3, 2

Expected Response and Monitoring

• Recheck CBC at 2 weeks: Hemoglobin should rise ≥10 g/L within 2 weeks, confirming iron deficiency 1, 2
• Monitor hemoglobin and red cell indices every 3 months for 1 year, then annually 1, 3, 2
• Provide additional oral iron if hemoglobin or MCV falls below normal during follow-up 1, 3

When to Consider Alternative Diagnoses or Treatments

Failure to Respond to Oral Iron (After 4 Weeks)

If hemoglobin does not increase by at least 2 g/dL within 4 weeks, consider: 1, 2

• Non-compliance with medication
• Ongoing blood loss exceeding replacement capacity
• Malabsorption (celiac disease, inflammatory bowel disease, gastric bypass)
• Genetic disorders of iron metabolism or heme synthesis

Indications for Intravenous Iron

Switch to IV iron if: 1, 3, 2

• Documented malabsorption is present
• True intolerance to all oral formulations exists
• Blood losses exceed maximal oral replacement capacity
• Expected response: Hemoglobin increase ≥2 g/dL within 4 weeks of IV iron 1, 3

Consider Genetic Disorders If:

• Extreme microcytosis (MCV <70) or family history of microcytic anemia 1
• Microcytosis with normal iron studies (ferritin >45 μg/L, normal TSAT) 1, 3
• MCV disproportionately low relative to degree of anemia 1
• Persistent microcytosis despite iron repletion 2

In these cases, order hemoglobin electrophoresis to evaluate for thalassemia trait 1, and consider genetic testing for disorders like SLC11A2, STEAP3, SLC25A38, ALAS2, or ABCB7 defects 1

Special Genetic Considerations

• X-linked sideroblastic anemia (ALAS2 defects): Trial pyridoxine (vitamin B6) 50-200 mg daily initially, with lifelong supplementation at 10-100 mg daily if responsive 1
• IRIDA (TMPRSS6 defects): Requires intravenous iron (iron sucrose or iron gluconate) as oral iron is typically ineffective 1
• Severe genetic disorders (SLC25A38 defects): May require hematopoietic stem cell transplantation as the only curative option 1

Critical Pitfalls to Avoid

• Do not assume all microcytic anemia is iron deficiency: Anemia of chronic disease, thalassemia, and sideroblastic anemia must be differentiated to avoid unnecessary iron therapy 1
• Do not overlook combined deficiencies: Iron deficiency can coexist with B12 or folate deficiency 1, 3, 2
• Do not stop iron therapy when hemoglobin normalizes: Continue for 3 months to replenish stores 1, 2
• Do not ignore normal or elevated ferritin with microcytic anemia: This suggests anemia of chronic disease or a genetic disorder rather than simple iron deficiency 2