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

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From the Guidelines

The main causes of microcytic anemia, excluding common causes like iron deficiency, thalassemia, anemia of chronic disease, and some hemoglobinopathies, are genetic disorders of iron metabolism or heme synthesis, such as sideroblastic anemia, which can be inherited or acquired. These conditions result in smaller-than-normal red blood cells (microcytosis) with reduced hemoglobin content, leading to decreased oxygen-carrying capacity and symptoms like fatigue, weakness, and pallor. Proper diagnosis requires laboratory tests including complete blood count, iron studies, and sometimes genetic testing to determine the specific cause and guide appropriate treatment, 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. Some key features that may indicate these disorders include elevation of ferritin and/or transferrin saturation (TSAT) or low TSAT in combination with low-normal ferritin levels, family history, anemia that is refractory or incompletely responsive to iron supplementation, and features such as neurologic disease and skin photosensitivity 1. It is essential to integrate clinical and molecular insights into daily practice to avoid unnecessary delay in diagnosis, invasive or costly diagnostic tests, and harmful treatments, and to recognize that in some genetic anemias, such as the sideroblastic anemias, iron overload is of greater consequence than the anemia itself 1. The treatment of patients with microcytic anemia due to pathogenic SLC11A2 defects should include oral iron supplementation and/or EPO and/or erythrocyte transfusions, according to the needs of the individual patient, with monitoring of iron status to detect toxic iron loading at an early stage 1. Key considerations in the diagnosis and management of these conditions include:

  • Genetic testing to identify specific defects in genes involved in iron metabolism or heme synthesis
  • Laboratory tests, such as complete blood count, iron studies, and sometimes genetic testing
  • Monitoring of iron status to detect toxic iron loading at an early stage
  • Consideration of MRI of the liver to detect liver iron loading in patients with SLC11A2 defects.

From the Research

Main Causes of Microcytic Anemia

The main causes of microcytic anemia include:

  • Iron deficiency anemia, which is the most common cause of microcytic anemia 2, 3, 4
  • Thalassemia, a genetic disorder that affects the production of hemoglobin 3
  • Anemia of chronic disease, which can be caused by chronic inflammation or infection 5
  • Sideroblastic anemia, a rare disorder that affects the production of hemoglobin 3
  • Other causes, such as bleeding, impaired iron absorption, and inadequate dietary iron intake 4

Risk Factors for Iron Deficiency Anemia

Risk factors for iron deficiency anemia include:

  • Menstrual bleeding 2, 4
  • Pregnancy 2, 4
  • Gastrointestinal bleeding 2, 4
  • Inflammatory bowel disease (IBD) 4
  • Chronic kidney disease (CKD) 4
  • Heart failure (HF) 4
  • Cancer 4

Diagnosis of Microcytic Anemia

Diagnosis of microcytic anemia is based on:

  • Mean corpuscular volume (MCV) less than 80 mcm3 in adults 3
  • Serum ferritin levels less than 30 ng/mL 4
  • Transferrin saturation less than 20% 4
  • Reticulocyte hemoglobin content (Ret Hb) less than 27 pg/mL 5
  • Bone marrow examination to rule out other causes of microcytic anemia 2, 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Anemia: Microcytic Anemia.

FP essentials, 2023

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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