How to manage a patient newly diagnosed with microcytic anemia?

Management of Newly Diagnosed Microcytic Anemia

Start with oral ferrous sulfate 200 mg three times daily (providing 65 mg elemental iron per dose) for at least three months after hemoglobin correction, as this treats the most common cause—iron deficiency anemia—and serves as both diagnostic and therapeutic intervention. 1, 2

Initial Diagnostic Workup

Measure serum ferritin as the single most specific test:

• Ferritin <15 μg/L confirms absent iron stores 1
• Ferritin <30 μg/L indicates low body iron stores 1
• Use 45 μg/L as the optimal cut-off for sensitivity and specificity in practice 1, 2
• Ferritin >45 μg/L with microcytosis suggests alternative diagnoses 1

Assess transferrin saturation (TSAT) and red cell distribution width (RDW):

• Low TSAT with low ferritin confirms iron deficiency 1
• RDW >14.0% with low MCV suggests iron deficiency anemia 1, 2
• RDW ≤14.0% with low MCV suggests thalassemia minor 1, 2
• Elevated ferritin and/or TSAT with microcytosis indicates genetic disorders of iron metabolism or heme synthesis 3

First-Line Treatment Algorithm

For presumed iron deficiency (ferritin <45 μg/L):

• Prescribe ferrous sulfate 324 mg tablets (65 mg elemental iron) three times daily 1, 2, 4
• Add ascorbic acid to enhance absorption 1, 2
• Alternative formulations if intolerance: ferrous gluconate or ferrous fumarate 1

Confirm diagnosis by therapeutic response:

• Expect hemoglobin rise ≥10 g/L (≥1 g/dL) within 2 weeks 1, 2
• Hemoglobin increase ≥2 g/dL within 4 weeks confirms iron deficiency 1
• Continue treatment for minimum 3 months after anemia correction to replenish stores 1, 2

Management of Non-Responsive Cases

If no response to oral iron after 2-4 weeks, investigate:

• Malabsorption requiring intravenous iron 1, 2
• Thalassemia (especially if RDW normal/near-normal) 1, 2
• Genetic disorders of iron metabolism or heme synthesis 1, 2
• Combined deficiencies (coexisting B12 or folate deficiency) 2, 5

For confirmed genetic disorders:

• ALAS2 defects (X-linked sideroblastic anemia): Start pyridoxine 50-200 mg daily, then maintain lifelong at 10-100 mg daily 1, 5
• TMPRSS6 defects (IRIDA): Use intravenous iron (iron sucrose or ferric gluconate) repeatedly; oral iron usually fails 1, 2
• SLC25A38 defects: Hematopoietic stem cell transplantation is the only curative option; symptomatic treatment includes transfusions and chelation 1, 5
• STEAP3 defects: Erythrocyte transfusions combined with erythropoietin, plus chelation for iron overload 1, 5

Monitoring Protocol

During treatment phase:

• Recheck hemoglobin at 2 weeks to confirm response 1, 2
• Monitor hemoglobin and MCV at 3-month intervals for one year, then annually 1
• Measure serum ferritin and TSAT to assess iron store repletion 1

Critical pitfall to avoid:

• In genetic sideroblastic anemias, iron overload causes greater morbidity and mortality than the anemia itself 3
• Monitor ferritin levels; do not exceed 500 μg/L to prevent toxic iron loading 1, 2
• Consider liver MRI to detect early iron loading, as normal ferritin doesn't exclude hepatic iron accumulation 1, 5

Iron Overload Management

For patients requiring chronic transfusions or developing iron overload:

• Phlebotomy is preferred when tolerated 2, 5
• Iron chelation therapy when phlebotomy not tolerated 2, 5
• Regular monitoring of ferritin, TSAT, and liver enzymes 2, 5

Family Screening Considerations

Pursue genetic testing and counseling when:

• Family history of refractory anemia 3
• Anemia incompletely responsive to iron supplementation 3
• Associated neurologic disease or skin photosensitivity 3
• Low TSAT with low-normal ferritin (>20 mg/L) 3
• Screen family members for hereditary forms 2, 5