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

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From the Guidelines

Chronic microcytosis is most commonly caused by genetic disorders of iron metabolism or heme synthesis, such as sideroblastic anemia, which involves defective heme synthesis resulting in iron accumulation in red blood cell precursors 1.

Causes of Chronic Microcytosis

The causes of chronic microcytosis can be complex and varied, but they often involve defects in iron metabolism or heme synthesis. Some of the key causes include:

  • Sideroblastic anemia, which is characterized by the accumulation of iron in red blood cell precursors 1
  • Genetic disorders of iron metabolism, such as mutations in the TMPRSS6 gene, which can lead to a mild IRIDA phenotype 1
  • Defects in heme synthesis, such as those caused by mutations in the ALAS2 gene, which can lead to X-linked sideroblastic anemia 1

Diagnosis and Treatment

Diagnosis of chronic microcytosis typically requires a complete blood count, peripheral blood smear, iron studies, and sometimes hemoglobin electrophoresis or genetic testing 1. Treatment depends on identifying and addressing the underlying cause, such as iron supplementation for deficiency or specific management for genetic disorders 1.

Key Considerations

It is essential to exclude common causes of microcytic anemia, such as iron deficiency, anemia of chronic disease, and thalassemia, before considering genetic disorders of iron metabolism or heme synthesis 1. Additionally, patients with microcytic anemia due to pathogenic SLC11A2 defects should be treated with oral iron supplementation and/or EPO and/or erythrocyte transfusions, according to the needs of the individual patient, and iron status should be monitored to detect toxic iron loading at an early stage 1.

From the Research

Causes of Chronic Microcytosis

  • Iron deficiency anemia is the most common cause of microcytosis, as stated in 2 and 3
  • Thalassemia trait is another common cause of microcytosis, as mentioned in 2
  • Anemia of chronic disease is also a possible cause, characterized by low iron levels and decreased total iron-binding capacity, as discussed in 2 and 4
  • Lead toxicity and sideroblastic anemia are other potential causes of microcytosis, as noted in 2

Diagnosis and Evaluation

  • Serum ferritin measurement is the first laboratory test recommended in the evaluation of microcytosis, as stated in 2
  • Low ferritin levels suggest iron deficiency, while elevated levels of hemoglobin A2 are indicative of beta-thalassemia trait, as mentioned in 2
  • Further evaluation may include total iron-binding capacity, transferrin saturation level, and serum iron level, as discussed in 2 and 3

Management and Treatment

  • Iron therapy is a common treatment for iron deficiency anemia, with oral iron supplements being the first line of treatment, as discussed in 3 and 5
  • Intravenous iron may be necessary for patients with malabsorption, ongoing blood loss, or certain chronic inflammatory conditions, as mentioned in 3, 6, and 5
  • Erythropoiesis stimulating agents (ESAs) may also be used in the management of anemia of chronic disease, as discussed in 4 and 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Evaluation of microcytosis.

American family physician, 2010

Related Questions

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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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