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.