What is the treatment approach for microcytosis?

Treatment Approach for Microcytosis

The treatment of microcytosis depends entirely on identifying the underlying cause—first exclude iron deficiency with serum ferritin (<30 μg/L indicates deficiency), then differentiate between thalassemia trait, anemia of chronic disease, and rare genetic disorders, as each requires fundamentally different management strategies. 1

Initial Diagnostic Algorithm

Step 1: Measure serum ferritin as the first-line test 1

• Ferritin <30 μg/L confirms iron deficiency anemia and warrants immediate treatment 2, 1
• Ferritin 30-100 μg/L in the presence of inflammation may still represent iron deficiency 1
• Normal or elevated ferritin points toward thalassemia trait or other causes 2

Step 2: Evaluate red blood cell count and RDW to narrow the differential 2

• Elevated RBC count (>5.0 million/μL) with microcytosis strongly suggests thalassemia trait, not iron deficiency 2
• Elevated RDW (>14.0%) with low RBC count indicates iron deficiency 2, 1
• Normal RDW (≤14.0%) with microcytosis suggests thalassemia trait 1

Step 3: If ferritin is normal/high, obtain additional iron studies 1, 3

• Low iron with low TIBC and normal/high ferritin indicates anemia of chronic disease 1
• Hemoglobin electrophoresis showing HbA2 >3.5% confirms beta-thalassemia trait 4

Treatment Based on Etiology

Iron Deficiency Anemia (Ferritin <30 μg/L)

Oral iron supplementation is first-line therapy 1, 5

• Ferrous sulfate 200 mg three times daily (or 65 mg elemental iron daily) for at least 3 months after anemia correction 1, 5
• Adding ascorbic acid (vitamin C) enhances iron absorption 4, 1
• Expected hemoglobin response within 2 weeks of starting therapy 5

Investigate the source of iron loss—this is mandatory 1, 5

• In men and post-menopausal women, gastrointestinal blood loss is the primary concern and malignancy must be excluded 1, 5
• Upper endoscopy with small bowel biopsies and colonoscopy are required to screen for celiac disease, gastric cancer, peptic ulcers, colorectal cancer, and inflammatory bowel disease 5
• In pre-menopausal women, consider menstrual blood loss, but still investigate GI tract if losses seem excessive 1

Consider intravenous iron in specific situations 1, 5

• Malabsorption (celiac disease, inflammatory bowel disease, previous gastrectomy) 1
• Intolerance to oral iron 1
• Blood losses exceeding oral replacement capacity 5
• Severe anemia with cardiovascular compromise 5

Monitor response to therapy 1

• Check hemoglobin and red cell indices at 3-month intervals for one year, then annually 1
• Continue iron therapy until ferritin >100 ng/mL to replete stores 5

Thalassemia Trait (Normal/High Ferritin, Elevated RBC Count)

Do NOT give iron supplementation 2

• Iron therapy in thalassemia trait patients can cause iron overload and is contraindicated unless concurrent iron deficiency is documented 2
• This is a critical pitfall—assuming all microcytosis is iron deficiency leads to inappropriate and harmful iron supplementation 2

Provide genetic counseling and family screening 4, 2

• Offer partner testing if reproductive planning is relevant, as homozygous thalassemia in offspring can be severe 2
• Screen first-degree family members 4
• Referral to clinical geneticist is recommended for complex cases 4

No specific treatment is required for trait carriers 4

• Thalassemia trait is generally asymptomatic and does not require intervention 4
• If mild anemia is present, treatment is not recommended 4

Genetic Disorders of Iron Metabolism (IRIDA and Others)

For IRIDA (Iron-Refractory Iron Deficiency Anemia) 4

• Oral iron is typically ineffective due to severe TMPRSS6 defects 4
• Intravenous iron (iron sucrose or iron gluconate) is the treatment of choice, though complete normalization of hemoglobin is seldom achieved 4
• Ascorbic acid (3 mg per day) with oral ferrous sulfate may improve response in some infants 4

For severe genetic disorders with transfusion dependence 4

• Chronic erythrocyte transfusion for symptomatic treatment 4
• Iron chelation according to guidelines for chronic transfusions to prevent iron overload 4
• Allogeneic hematopoietic stem cell transplant (HSCT) should be considered as the only curative treatment for severe cases like congenital erythropoietic porphyria 4

Monitor for iron overload in genetic disorders 1

• Older patients with genetic disorders are more likely to develop iron overload from increased ineffective erythropoiesis, iron supplementation, and transfusions 4
• Monitor transferrin saturation (TSAT) and ferritin regularly 1

Critical Pitfalls to Avoid

Never start empiric iron therapy without confirming iron deficiency 2

• The combination of elevated RBC count with microcytosis should immediately raise suspicion for thalassemia trait, not iron deficiency 2
• Check ferritin first to avoid causing iron overload in thalassemia patients 2

Always investigate the source of iron deficiency in adults 1, 5

• Failure to perform endoscopic evaluation in men and post-menopausal women can miss gastrointestinal malignancy 5
• This is particularly critical as GI blood loss is the most common cause in these populations 1, 5

Do not overlook combined deficiency states 5

• Elevated RDW with microcytosis may indicate concurrent folate or B12 deficiency masking the full picture 5
• Check folate and B12 levels if RDW is disproportionately elevated 5

Provide genetic counseling for confirmed thalassemia trait 2

• Failing to offer family screening and reproductive counseling is a critical oversight with significant implications for future generations 2