Acquired Refractory Iron Deficiency Anemia

Margherita Migone De Amicis, Alessandro Rimondi, Luca Elli, Irene Motta

Research output: Contribution to journalReview articlepeer-review


Anemia is a global health problem affecting one-third of the world population, and half of the cases are due to iron deficiency (ID). Iron deficiency anemia (IDA) is the leading cause of disability in several countries. Although multiple mechanisms may coexist, ID and IDA causes can be classified as i) insufficient iron intake for the body requirement, ii) reduced absorption, and iii) blood losses. Oral iron represents the mainstay of IDA treatment. IDA is defined as "refractory" when the hematologic response after 4 to 6 weeks of treatment with oral iron (an increase of >=1 g/dL of Hb) is absent. The cause of iron-refractory anemia is usually acquired and frequently related to gastrointestinal pathologies, although a rare genetic form called iron-refractory iron deficiency anemia (IRIDA) exists. In some pathological circumstances, either genetic or acquired, hepcidin increases, limiting the absorption in the gut, remobilization, and recycling of iron, thereby reducing iron plasma levels. Indeed, conditions with high hepcidin levels are often under-recognized as iron refractory, leading to inappropriate and unsuccessful treatments. This review provides an overview of the iron refractory anemia underlying conditions, from gastrointestinal pathologies to hepcidin dysregulation and iatrogenic or provoked conditions, and the specific diagnostic and treatment approach.

Original languageEnglish
Article numbere2021028
JournalMediterranean Journal of Hematology and Infectious Diseases
Issue number1
Publication statusPublished - Apr 29 2021


  • Bleeding
  • Hepcidin
  • Intravenous iron
  • Iron deficiency
  • Iron refractory anemia
  • Malabsorption

ASJC Scopus subject areas

  • Hematology
  • Infectious Diseases


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