What is the management approach for a patient with a complete blood count (CBC) showing microcytosis?

Management of Microcytic Anemia

The diagnostic workup for microcytic anemia should begin with serum ferritin measurement as it is the most powerful test for iron deficiency, followed by appropriate treatment of the underlying cause. 1, 2, 3

Initial Diagnostic Evaluation

• Serum ferritin is the most specific test for iron deficiency in the absence of inflammation, with levels <30 μg/L indicating iron deficiency 1, 2
• In the presence of inflammation, serum ferritin up to 100 μg/L may still be consistent with iron deficiency 1
• Additional iron studies should include:
  • Serum iron 3
  • Total iron binding capacity (TIBC) 3
  • Transferrin saturation (TSAT) - values <16% suggest iron deficiency 2
• A low MCV with elevated red cell distribution width (RDW >14.0%) suggests iron deficiency anemia 3
• A low MCV with normal RDW (≤14.0%) suggests thalassemia trait 3

Differential Diagnosis

• Iron deficiency anemia - most common cause of microcytic anemia 4, 5
• Thalassemia trait - consider if iron studies are normal 2, 4
• Anemia of chronic disease - characterized by low iron, low TIBC, and normal/high ferritin 2, 3
• Genetic disorders of iron metabolism or heme synthesis:
  • SLC11A2 defects - consider in patients with unexplained microcytic anemia with increased TSAT 1
  • STEAP3 defects - consider in patients with unexplained hypochromic sideroblastic anemia 1
  • SLC25A38 defects - consider in children with severe unexplained microcytic sideroblastic anemia 1
  • ABCB7 defects - consider in male patients with mild microcytic anemia and ataxia 1
  • ALAS2 defects - consider in patients with pyridoxine-responsive or unresponsive microcytic sideroblastic anemia 1

Investigation of Underlying Causes

• In men and post-menopausal women, investigate for gastrointestinal blood loss as it is the most common cause of iron deficiency anemia 1
• Other causes to consider include:
  • Menstrual blood loss in pre-menopausal women 1
  • Malabsorption (most frequently from celiac disease) 1
  • Poor dietary intake 1
  • Previous gastrectomy 1
  • NSAID use 1

Treatment Approach

For Iron Deficiency Anemia:

• First-line treatment: oral iron supplementation for at least three months after correction of anemia 3
  • Ferrous sulfate 200 mg three times daily is standard dosing 3
  • Alternative formulations include ferrous gluconate and ferrous fumarate if ferrous sulfate is not tolerated 3
  • Adding ascorbic acid can enhance iron absorption 2, 3
• A good response to iron therapy is defined as a hemoglobin rise ≥10 g/L within a 2-week timeframe 3
• For patients who fail to respond to oral iron therapy, consider intravenous (IV) iron if there is malabsorption 3

For Genetic Disorders:

• Patients with SLC11A2 defects should be treated with oral iron supplementation and/or erythropoietin (EPO) and/or erythrocyte transfusions, according to individual needs 1
• For SLC25A38 defects, hematopoietic stem cell transplantation (HSCT) is the only curative option; symptomatic treatment consists of erythrocyte transfusions and chelation therapy 1
• For ABCB7 defects, treatment of mild anemia is generally not indicated 1
• For ALAS2 defects, management should involve treatment of anemia and prevention/treatment of iron overload 1

Monitoring and Follow-up

• Monitor hemoglobin concentration and red cell indices at three-month intervals for one year and then after a further year 3
• In patients receiving iron therapy for genetic disorders, monitor iron status to detect toxic iron loading early 1
• For SLC11A2 defects, consider MRI of the liver as normal serum ferritin does not exclude liver iron loading 1

Special Considerations

• Genetic testing should be considered in patients with refractory microcytic anemia despite adequate iron supplementation 3
• Family screening may be recommended for patients diagnosed with genetic disorders affecting iron metabolism 1, 3
• Avoid overlooking combined deficiencies, such as iron deficiency coexisting with B12 or folate deficiency, which may result in a normal MCV 1, 3