Microcytic Hypochromic Anemia Causes and Considerations

Primary Causes

Microcytic hypochromic anemia is primarily caused by nutritional iron deficiency, iron loss from gastrointestinal disease, iron malabsorption, hemoglobinopathies, and severe anemia of chronic disease 1
Anemia of chronic disease causes functional iron deficiency through iron sequestration rather than true depletion, characterized by elevated ferritin with low serum iron, particularly significant in hospitalized patients and elderly populations 2

When ferritin is elevated and/or transferrin saturation is abnormal, or when anemia is refractory to iron supplementation, consider genetic disorders of iron metabolism or heme synthesis, such as iron refractory iron-deficiency anemia, hypotransferrinemia, and DMT1 deficiency 1
DMT1 deficiency causes anemia with paradoxical systemic iron loading, presenting at birth with microcytic anemia and increased transferrin saturation, and liver iron loading develops despite normal or mildly increased ferritin 3
SLC25A38 deficiency causes severe congenital sideroblastic anemia, presenting with transfusion-dependent microcytic hypochromic anemia in childhood, and bone marrow shows ring sideroblasts with elevated ferritin and transferrin saturation 1, 3

Do not start empiric oral iron therapy when ferritin is elevated, as this could worsen iron overload in sideroblastic anemia or genetic disorders 2
Family history of anemia refractory to iron supplementation, neurologic disease, or skin photosensitivity should raise suspicion for genetic disorders 1
Serum ferritin may be elevated in inflammatory conditions despite concurrent iron deficiency, potentially masking true iron depletion 2