What is the workup for microcytic anemia (small red blood cell anemia)?

From the Guidelines

The workup for microcytic anemia should begin with a complete blood count (CBC) with peripheral smear, serum iron studies (including ferritin, iron, total iron binding capacity, and transferrin saturation), and hemoglobin electrophoresis, as recommended by the practice guidelines for the diagnosis and management of microcytic anemias due to genetic disorders of iron metabolism or heme synthesis 1.

Key Steps in the Workup

• Measuring ferritin is essential, with levels below 30 ng/mL strongly suggesting iron deficiency, which is the most common cause of microcytic anemia.
• Additional tests should include reticulocyte count to assess bone marrow response and a stool occult blood test to screen for gastrointestinal bleeding, a common source of iron loss.
• If thalassemia is suspected based on family history or ethnicity, hemoglobin electrophoresis is crucial.
• For anemia of chronic disease with iron sequestration, addressing the underlying condition is paramount.
• In cases of lead poisoning, which can also cause microcytic anemia, blood lead levels should be checked in at-risk populations.

Consideration of Genetic Disorders

• In patients with unexplained microcytic anemia, consideration should be given to genetic disorders of iron metabolism or heme synthesis, such as IRIDA due to a TMPRSS6 defect, which can be diagnosed with certainty only when the patient is homozygous or compound heterozygous for a pathogenic mutation 1.
• Determination of serum hepcidin and TMPRSS6 mutation analysis may be recommended in such cases.

Treatment Approach

• In cases where iron deficiency is confirmed, oral iron supplementation with ferrous sulfate 325 mg three times daily or ferrous gluconate 300 mg twice daily should be initiated, ideally taken on an empty stomach with vitamin C to enhance absorption, and treatment typically continues for 3-6 months after hemoglobin normalizes to replenish iron stores 1.
• For patients with microcytic anemia due to pathogenic SLC11A2 defects, treatment with oral iron supplementation and/or EPO and/or erythrocyte transfusions may be necessary, according to the needs of the individual patient.

From the Research

Workup for Microcytic Anemia

The workup for microcytic anemia involves several steps to determine the underlying cause of the condition.

• The first step is to measure the mean corpuscular volume (MCV) to confirm the presence of microcytic anemia, which is typically defined as an MCV of less than 80 µm3 (80 fL) in adults 2, 3.
• The next step is to measure serum ferritin levels, which is the best single laboratory parameter for the diagnosis of iron deficiency anemia 4, 5, 6.
• If serum ferritin levels are low, it suggests iron deficiency anemia, and further evaluation should focus on determining the underlying source of the deficiency, such as gastrointestinal bleeding or menstrual bleeding in women 4, 2.
• If serum ferritin levels are not low, further evaluation should include total iron-binding capacity, transferrin saturation level, serum iron level, and possibly hemoglobin electrophoresis to differentiate between other causes of microcytic anemia, such as thalassemia or anemia of chronic disease 2, 6.
• Other tests that may be used to assess iron deficiency include serum transferrin receptor, transferrin receptor-ferritin index, and zinc-protoporphyrin concentration in erythrocytes 6.
• In some cases, a bone marrow biopsy may be necessary to evaluate body iron stores and confirm the diagnosis of iron deficiency anemia 4, 6.
• Hemoglobin electrophoresis is required for the diagnosis of hemoglobinopathy, such as beta-thalassemia or hemoglobinopathy E 3, 6.

Common Causes of Microcytic Anemia

The most common causes of microcytic anemia include:

• Iron deficiency anemia, which is the most common type of microcytic anemia and can be caused by inadequate iron intake, increased iron requirements, or chronic blood loss 4, 2, 5, 3, 6.
• Thalassemia, which is a genetic disorder that affects the production of hemoglobin and can cause microcytic anemia 2, 3, 6.
• Anemia of chronic disease, which can cause microcytic anemia due to inflammation and impaired iron utilization 2, 6.
• Sideroblastic anemia, which is a rare disorder that affects the production of hemoglobin and can cause microcytic anemia 3, 6.
• Lead toxicity, which can cause microcytic anemia due to impaired heme synthesis 2.