1 General Medicine Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy.
2 Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
3 Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
4 Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
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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.
|Table 1. Definitions related to iron deficiency.
|Figure 1. Causes of iron
refractory iron deficiency anemia. IRIDA: Iron refractory iron
deficiency anemia; IBD: Inflammatory bowel diseases.
Autoimmune Atrophic Gastritis
Occult Blood Losses
Drug-Related Iron Refractory Anemia
Iron Refractory Anemia and Hepcidin Dysregulation
|Figure 2. Characteristics, indications, and side effects of oral and IV iron formulation.
|Table 2. Characteristics, indications, and side effects of oral and IV iron formulation.|
|Table 3. Diagnostic work-up and treatment of specific conditions causing iron refractory anemia.|