Iron and anemia in human biology: a review of mechanisms

Heart Fail Rev. 2008 Dec;13(4):393-404. doi: 10.1007/s10741-008-9086-x. Epub 2008 Mar 25.


The biology of iron in relation to anemia is best understood by a review of the iron cycle, since the majority of iron for erythropoiesis is provided by iron recovered from senescent erythrocytes. In iron-deficiency anemia, storage iron declines until iron delivery to the bone marrow is insufficient for erythropoiesis. This can be monitored with clinical indicators, beginning with low plasma ferritin, followed by decreased plasma iron and transferrin saturation, and culminating in red blood cells with low-Hb content. When adequate dietary iron is provided, these markers show return to normal, indicating a response to the dietary supplement. Anemia of inflammation (also known as anemia of chronic disease, or ACD) follows a different course, because in this form of anemia storage iron is often abundant but not available for erythropoiesis. The diagnosis of ACD is more difficult than the diagnosis of iron-deficiency anemia, and often the first identified symptom is the failure to show a response to a dietary iron supplement. Confirmation of ACD is best obtained from elevated markers of inflammation. The treatment of ACD, which typically employs erythropoietin (EPO) supplements and intravenous iron (i.v.-iron), is empirical and often falls shorts of therapeutic goals. Dialysis patients show a complex pattern of anemia, which results from inadequate EPO production by the kidney, inflammation, changes in nutrition, and blood losses during treatment. EPO and i.v.-iron are the mainstays of treatment. Patients with heart failure can be anemic, with incidence as high as 50%. The causes are multifactorial; inflammation now appears to be the primary cause of this form of anemia, with contributions from increased plasma volume, effects of drug therapy, and other complications of heart disease. Discerning the mechanisms of anemia for the heart failure patient may aid rational therapy in each case.

Publication types

  • Review

MeSH terms

  • Anemia / etiology*
  • Anemia / metabolism
  • Anemia / physiopathology*
  • Anemia, Iron-Deficiency / physiopathology
  • Chronic Disease
  • Epoetin Alfa
  • Erythropoietin / therapeutic use
  • Female
  • Heart Diseases / complications
  • Hematinics / therapeutic use
  • Humans
  • Inflammation / complications
  • Iron / metabolism*
  • Iron / therapeutic use
  • Kidney Diseases / complications
  • Male
  • Recombinant Proteins


  • Hematinics
  • Recombinant Proteins
  • Erythropoietin
  • Epoetin Alfa
  • Iron