What are the next steps in managing a patient with microcytic anemia?

Follow-Up Management of Microcytic Anemia

After identifying microcytic anemia, immediately measure serum ferritin, transferrin saturation (TSAT), complete blood count with RDW, and examine the peripheral smear to differentiate iron deficiency from thalassemia trait and genetic disorders of iron metabolism. 1

Initial Diagnostic Algorithm

Step 1: Assess Iron Parameters and RBC Indices

• Serum ferritin is the single most useful marker: A level <15 μg/L confirms absent iron stores with 99% specificity, while <30 μg/L indicates low body iron stores 1, 2, 3
• Use a ferritin cutoff of 45 μg/L for optimal sensitivity/specificity, particularly when inflammatory conditions may be present 1, 2
• RDW is critical for differentiation: RDW >14.0% with low MCV strongly suggests iron deficiency anemia, while RDW ≤14.0% points toward thalassemia trait 1, 2
• TSAT is more sensitive than hemoglobin alone for detecting iron deficiency 1

Step 2: Interpret Results and Proceed Based on Pattern

If ferritin is low (<45 μg/L) with elevated RDW:

• Diagnose iron deficiency anemia and immediately investigate the source of iron loss (gastrointestinal bleeding, menstrual losses, malabsorption) 1, 3
• Start ferrous sulfate 200 mg (65 mg elemental iron) three times daily for at least 3 months after anemia correction to replenish iron stores 1, 4, 2
• Expect hemoglobin increase of at least 2 g/dL within 4 weeks of starting oral iron 1
• Consider adding ascorbic acid to enhance iron absorption 2

If ferritin is normal/elevated (>20 μg/L) with normal RDW:

• Order hemoglobin electrophoresis immediately to evaluate for thalassemia trait, particularly in patients with Mediterranean, African, Middle Eastern, or Southeast Asian ancestry 1
• An MCV disproportionately reduced relative to the degree of anemia strongly suggests thalassemia 5, 1
• For thalassemia trait: no iron supplementation is indicated unless concurrent iron deficiency is documented; provide genetic counseling 1, 4

If ferritin is low-to-normal (>20 μg/L) with low TSAT:

• Consider genetic disorders of iron metabolism or heme synthesis, particularly if there is family history, refractoriness to oral iron, or associated features like neurologic disease or photosensitivity 5
• Refer for genetic testing and specialized hematology evaluation 5, 4

Management of Specific Genetic Disorders

Iron-Refractory Iron Deficiency Anemia (IRIDA)

• Most patients present in childhood with microcytic anemia, remarkably low TSAT, and low-to-normal ferritin 5
• Initial treatment: oral iron or oral iron combined with ascorbic acid 2
• Monitor serum ferritin levels to avoid toxicity of iron overload (should not exceed 500 μg/L) 2
• Exclude autoimmune atrophic gastritis, H. pylori infection, or celiac disease, which can mimic IRIDA 5

X-Linked Sideroblastic Anemia (ALAS2 defects)

• Initial treatment with pyridoxine 50-200 mg per day is recommended 4
• For pyridoxine-responsive cases, lifelong supplementation at 10-100 mg daily with regular monitoring for iron overload 4
• Check iron parameters (ferritin, TSAT) and liver enzymes regularly 5, 4

Sideroblastic Anemia Due to SLC25A38 Defects

• Hematopoietic stem cell transplantation (HSCT) is the only curative option 5, 4
• Symptomatic treatment consists of erythrocyte transfusions and chelation therapy 5, 4

Other Genetic Disorders

• STEAP3 defects: Treat with erythrocyte transfusions combined with EPO; manage systemic iron loading with chelation therapy 5, 4
• SLC11A2 defects: Treat with oral iron supplementation and/or EPO and/or erythrocyte transfusions according to individual needs; monitor iron status to detect toxic iron loading early 5, 4
• GLRX5 defects: Monitor iron status and treat iron loading with chelation therapy; severe anemia requires blood transfusions 5, 4

Management of Iron Overload

• Phlebotomy is the preferred method for managing iron overload when tolerated 4, 2
• Iron chelation therapy is recommended when phlebotomies are not tolerated due to decreasing hemoglobin 5, 4, 2
• Consider MRI of the liver to assess iron loading, especially in patients with SLC11A2 defects, as normal serum ferritin doesn't exclude liver iron loading 4, 2

Monitoring and Follow-Up

• Monitor hemoglobin and red cell indices at 3-month intervals for one year, then annually 1
• For genetic forms, monitor for complications specific to the disorder with regular assessment of iron status 4, 2
• In cases of iron supplementation or transfusions, monitor for iron overload 4, 2

Critical Pitfalls to Avoid

• Do not assume all microcytic anemia is iron deficiency—consider thalassemia and genetic disorders, especially with extremely low MCV 1, 6
• Do not give iron supplementation empirically without confirming iron deficiency, as this can cause harm in thalassemia and genetic iron metabolism disorders 1
• Do not overlook combined deficiencies, such as iron deficiency coexisting with B12 or folate deficiency 2
• In genetic anemias, particularly sideroblastic anemias, iron overload is often of greater consequence than the anemia itself; unrecognized tissue iron loading can lead to severe morbidity and mortality 5

Family Screening and Genetic Counseling

• Family screening and genetic counseling are important for hereditary forms of microcytic anemia 4, 2
• For autosomal recessive disorders, screen first-degree family members and offer genetic counseling 5
• For X-linked disorders, inform about inheritance patterns and screen appropriate family members based on the specific genetic defect 5