What are the causes of microcytic anemia (small red blood cell anemia)?

From the Guidelines

Microcytic anemia is primarily caused by genetic disorders of iron metabolism or heme synthesis, excluding common causes like iron deficiency, thalassemias, and hemoglobinopathies. The diagnosis of microcytic anemia due to genetic disorders of iron metabolism or heme synthesis involves a thorough clinical and laboratory assessment, including measuring serum iron, ferritin, total iron-binding capacity, and hemoglobin electrophoresis 1. According to the practice guidelines for the diagnosis and management of microcytic anemias due to genetic disorders of iron metabolism or heme synthesis, published in the journal Blood in 2014, the diagnostic approach should classify anemia as microcytic, normocytic, or macrocytic, and microcytic anemias are primarily caused by nutritional iron deficiency, iron loss, or genetic disorders 1.

Some key points to consider in the diagnosis of microcytic anemia due to genetic disorders of iron metabolism or heme synthesis include:

• Photosensitivity, neurological disease, and isolated ataxia may be present in some cases
• Ferritin levels may be low or normal, and TSAT may be low or high
• Hemolysis may be present, and uroporphyrin and coproporphyrin accumulation in RBC, plasma, urine, and feces may be detected
• The severity of anemia may vary, and hepcidin/TSAT high ratio may be associated with mild to severe anemia
• FPP and ZnPP accumulation in RBC may be detected, and ceruloplasmin levels may be very low or undetectable

The guidelines also provide a diagnostic flowchart for microcytic anemias caused by inherited defects in iron metabolism or heme synthesis, which includes bone marrow smears or gene analysis 1. A definitive diagnosis can be made by identifying pathogenic mutations in the relevant genes, such as TMPRSS6, and by interpreting iron parameters in the context of the age of the patient and the given treatment 1.

From the Research

Causes of Microcytic Anemia

• Iron deficiency anemia is the most common cause of microcytic anemia, as stated in studies 2, 3, 4
• Other causes of microcytic anemia include:
  • Anemia of chronic disease 2, 4
  • Thalassemia 2, 3, 4
  • Sideroblastic anemia 2, 3
  • Sickle cell anemia 3

Diagnosis and Differentiation

• The absence of iron stores in the bone marrow is the most definitive test for differentiating iron deficiency from other microcytic states 2
• Measurement of serum ferritin, iron concentration, transferrin saturation, and iron-binding capacity can help diagnose iron deficiency anemia 2
• Serum transferrin receptors may also be used to diagnose iron deficiency anemia 2
• Low serum ferritin is the best single laboratory parameter for the diagnosis of iron deficiency 4

Underlying Causes of Iron Deficiency Anemia

• Disruptions in iron homeostasis, such as during menstruation, pregnancy, and gastrointestinal bleeding 2
• Malabsorption, losses exceeding maximal oral replacement, or true intolerance to oral iron preparations 2