What are the causes and diagnostic approaches for microcytic anemia (low Red Blood Cell (RBC) size)?

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From the Guidelines

Microcytic anemia is primarily caused by iron deficiency, though it can also result from thalassemia, anemia of chronic disease, sideroblastic anemia, or lead poisoning, and diagnosis begins with a complete blood count showing low hemoglobin levels and small red blood cells (MCV <80 fL) 1.

Causes of Microcytic Anemia

  • Iron deficiency: the most common cause worldwide, typically resulting from blood loss (menstruation, gastrointestinal bleeding), inadequate dietary intake, or poor absorption
  • Thalassemia: a genetic disorder affecting hemoglobin production
  • Anemia of chronic disease: resulting from chronic inflammation or disease
  • Sideroblastic anemia: a disorder affecting the production of hemoglobin
  • Lead poisoning: exposure to lead can cause microcytic anemia

Diagnosis of Microcytic Anemia

  • Complete blood count (CBC) showing low hemoglobin levels and small red blood cells (MCV <80 fL)
  • Serum ferritin: decreased in iron deficiency
  • Serum iron: low in iron deficiency
  • Total iron-binding capacity (TIBC): elevated in iron deficiency
  • Transferrin saturation: reduced in iron deficiency
  • Peripheral blood smear: may show hypochromic, microcytic red cells
  • Hemoglobin electrophoresis: to diagnose thalassemia
  • Blood lead levels: to diagnose lead poisoning
  • Inflammatory markers (CRP or ESR): to diagnose anemia of chronic disease

Treatment of Microcytic Anemia

  • Iron supplementation (typically ferrous sulfate 325mg orally three times daily for 3-6 months) for iron deficiency anemia, continuing even after hemoglobin normalizes to replenish iron stores 1.
  • Addressing the underlying cause of the anemia, such as treating gastrointestinal bleeding or inflammatory disease
  • Monitoring iron status to detect toxic iron loading in patients with genetic disorders of iron metabolism or heme synthesis 1
  • Considering MRI of the liver to detect liver iron loading in patients with SLC11A2 defects 1

From the Research

Causes of Microcytic Anaemia

  • Iron deficiency is the most common cause of microcytic anaemia 2, 3, 4, 5
  • Other causes include thalassemia, anemia of chronic disease, and sideroblastic anemia 2, 3, 4, 5
  • Disorders of iron metabolism, protoporphyrin and heme synthesis, as well as impaired globin synthesis, can also lead to microcytic anaemia 5
  • Microcytic anaemia can be acquired or congenital, and the cause should be considered separately according to the age of the patient, risk factors, and coexisting signs and symptoms 3

Diagnosis of Microcytic Anaemia

  • The diagnosis of microcytic anaemia is based on the presence of small, often hypochromic, red blood cells in a peripheral blood smear and a low mean corpuscular volume (MCV) 2, 3
  • 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 also help diagnose iron deficiency anaemia 2, 4, 5
  • Low serum ferritin is the best single laboratory parameter for the diagnosis of iron deficiency 4
  • New discriminative indices, such as low hemoglobin density (LHD) and microcytic anemia factor (MAF), can be used to differentiate between thalassemia trait and iron deficiency anaemia 6

Laboratory Tests for Microcytic Anaemia

  • Serum iron, total iron binding capacity, transferrin saturation, serum ferritin, and serum transferrin receptor can be used to assess iron deficiency 5
  • Hemoglobin electrophoresis is required for the diagnosis of hemoglobinopathy E 5
  • Examination of iron on aspirated bone marrow or marrow biopsy is the most precise method for evaluating body iron stores 5
  • Automated hematology analyzers can be used to determine peripheral blood parameters, such as LHD and MAF, to differentiate between thalassemia trait and iron deficiency anaemia 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Anemia: Microcytic Anemia.

FP essentials, 2023

Research

Microcytic anemia.

American family physician, 1997

Research

[Microcytic and hypochromic anemias].

Vnitrni lekarstvi, 2001

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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