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Disorders of iron metabolism. Part II: iron deficiency and iron overload
  1. Manuel Muñoz1,
  2. José Antonio García-Erce2,
  3. Ángel Francisco Remacha3
  1. 1Transfusion Medicine, School of Medicine, University of Malaga, Malaga, Spain
  2. 2Hematology and Hemotherapy, University Hospital Miguel Servet, Zaragoza, Spain
  3. 3Hematology and Hemotherapy, Complejo Hospitalario de Toledo, Toledo, Spain
  1. Correspondence to Professor Manuel Muñoz, Medicina Transfusional, Facultad de Medicina, Campus de Teatinos, s/n, 29071-Málaga, Spain; mmunoz{at}uma.es

Abstract

Main disorders of iron metabolism Increased iron requirements, limited external supply, and increased blood loss may lead to iron deficiency (ID) and iron deficiency anaemia. In chronic inflammation, the excess of hepcidin decreases iron absorption and prevents iron recycling, resulting in hypoferraemia and iron restricted erythropoiesis, despite normal iron stores (functional iron deficiency), and finally anaemia of chronic disease (ACD), which can evolve to ACD plus true ID (ACD+ID). In contrast, low hepcidin expression may lead to hereditary haemochromatosis (HH type I, mutations of the HFE gene) and type II (mutations of the hemojuvelin and hepcidin genes). Mutations of transferrin receptor 2 lead to HH type III, whereas those of the ferroportin gene lead to HH type IV. All these syndromes are characterised by iron overload. As transferrin becomes saturated in iron overload states, non-transferrin bound iron appears. Part of this iron is highly reactive (labile plasma iron), inducing free radical formation. Free radicals are responsible for the parenchymal cell injury associated with iron overload syndromes.

Role of laboratory testing in diagnosis In iron deficiency status, laboratory tests may provide evidence of iron depletion in the body or reflect iron deficient red cell production. Increased transferrin saturation and/or ferritin levels are the main cues for further investigation of iron overload. The appropriate combination of different laboratory tests with an integrated algorithm will help to establish a correct diagnosis of iron overload, iron deficiency and anaemia.

Review of treatment options Indications, advantages and side effects of the different options for treating iron overload (phlebotomy and iron chelators) and iron deficiency (oral or intravenous iron formulations) will be discussed.

  • Diagnosis
  • haemochromatosis
  • haematopoiesis
  • inflammation
  • iron metabolism

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Footnotes

  • Competing interests None to declare.

  • Provenance and peer review Commissioned; externally peer reviewed.

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