Iron‐Loading Anaemia

Abstract

This article outlines the key pathophysiologic factors underlying the three major forms of anaemia that are particularly likely to cause severe iron overload in patients, even without chronic transfusion therapy: the thalassaemia syndromes, sideroblastic anaemias and congenital dyserythropoietic anaemia. These forms of anaemia cause iron overload by impairing erythropoiesis in ways that cause accelerated turnover of developing erythroblasts in the marrow (ineffective erythropoiesis). The increased demand for non‐productive proliferation of erythroblasts disrupts the hepcidin‐mediated regulation of iron homeostasis. This leads to continued high levels of oral iron absorption despite the fact that iron from the destroyed erythroblasts cannot be excreted. As correction of the underlying illness is often not feasible, management usually focuses on judicious use of blood replacement and iron chelation.

Key Concepts

  • Iron is essential for aerobic life because it mediates the ability of oxygen to interact productively with the energy‐producing biochemical systems of the organism.
  • Iron is indispensable for haemoglobin and red cell production, and therefore, the oxygen tranportation system of the body.
  • Giving its essentiality for survival, iron stores are jealously protected by the body. Thus, there are no mechanisms for excreting iron, even when iron stores are present in excess amounts.
  • Almost all of the iron in the body is conserved by an intricate recycling mechanism from senescent red cells.
  • Absorption of new iron is intended to replace only the small amount of iron lost daily by bleeding and ell shedding.
  • Iron stores are regulated by controlling uptake from dietary sources. A complex endocrine system regulated by the hormone hepcidin plays the key role. In this regulatory cycle, increased erythroid activity in the marrow is interpreted to be a response to iron deficiency, even if iron stores are normal or high.
  • Iron‐overloading anaemias are those in which inefficient production of red cell results in excess iron absorption despite normal or elevated total body iron stores.
  • Ineffective erythropoiesis more severe than that seen in other anaemias is the hallmark of the major iron‐loading anaemias: thalassaemia, sideroblastic anaemias and congenital dyserythropietic anaemias.
  • These anaemias are not easily corrected at the mechanistic level so that iron chelation therapy, with or without red cell transfusion support, is usually necessary.

Keywords: iron; haemoglobin; haemochromatosis; anaemia; thalassaemia

Figure 1. Regulation of iron absorption by the intestinal enterocyte. (Reproduced from Andrews (2004) © Elsevier.)
Figure 2. The iron–transferrin cycle. Iron cycling (a) tissue and organ level and (b) at the cellular and intracellular level. (Reproduced from Andrews (2004) © Elsevier.)
Figure 3. Posttranscriptional regulation of tissue iron uptake, utilisation and storage by IRE. (Reproduced from Huang and Benz, with permission from Cambridge University Press.)
Figure 4. Possible role of hepcidin in regulating iron absorption. (Reproduced from Andrews (2004) © Elsevier.)
Figure 5. Haem biosynthesis. (Reproduced from Huang and Benz, with permission from Cambridge University Press.)
Figure 6. Pathophysiology of thalassaemia. The clinical manifestations of β thalassaemia are driven in the inclusion bodies found from excess α globin chains. Excess α globin can in turn result from impaired β globin production (β0, β+ thalassaemia) and /or excess α globin synthesis (ααα/αα, ααα/αα, αα/αα); conversely, (inheritance of α thalassaemia) (−−/αα, −α/αα) or increased γ globin can reduce excess α globin.
close

References

Alter BP (2003) Inherited bone marrow failure syndromes. In: Nathan DG, Orkin SH, Ginsburg D, et al. (eds) Nathan and Oski's Hematology of Infancy and Childhood, 6th edn, vol. 280, p. 365. Philadelphia: W.B. Saunders.

Andrews NC (2004) Pathology of iron metabolism. In: Hoffman R, Benz EJ Jr Shattil SJ, et al. (eds) Hematology: Basic Principles and Practice, 4th edn. Philadelphia: Elsevier Science.

Benz EJ Jr (2001) Hemoglobinopathies. In: Braunwald E, Fauci AS, Kasper DL, et al. (eds) Harrison's Principles of Internal Medicine, 156th edn, vol. 106, pp. 666–673. New York: McGraw‐Hill.

Brittenham G (2004) Disorders of iron metabolism. In: Hoffman R, Benz EJ Jr Shattil SJ, et al. (eds) Hematology: Basic Principles and Practice, 4th edn. Philadelphia: Elsevier Science.

Forget GB (2004) Thalassemia syndromes. In: Hoffman R, Benz EJ Jr Shattil SJ, et al. (eds) Hematology: Basic Principles and Practice, 4th edn. Philadelphia: Elsevier Science.

Huang SC and Benz EJ Jr (2003) Posttranscriptional factors influencing the hemoglobin content of the red cell. In: Steinberg M, Forget FG, Higgs DR, et al. (eds) Disorders of Hemoglobin, vol. 8, pp. 146–173. Cambridge, UK: Cambridge University Press.

Wiley JS and Moore MR (2004) Haem biosynthesis and its disorders. In: Hoffman R, Benz EJ Jr Shattil SJ, et al. (eds) Hematology: Basic Principles and Practice, 4th edn. Philadelphia: Elsevier Science.

Further Reading

Alter BP (2003) Inherited bone marrow failure syndromes. In: Nathan DG, Orkin SH, Ginsburg D, et al. (eds) Nathan and Oski's Hematology of Infancy and Childhood, 6th edn, vol. 280, p. 365. Philadelphia: W.B. Saunders.

Andrews NC (2004) Pathology of iron metabolism. In: Hoffman R, Benz EJ Jr Shattil SJ, et al. (eds) Hematology: Basic Principles and Practice, 4th edn. Philadelphia: Elsevier Science.

Benz EJ Jr (2001) Hemoglobinopathies. In: Braunwald E, Fauci AS, Kasper DL, et al. (eds) Harrison's Principles of Internal Medicine, 156th edn, vol. 106, pp. 666–673. New York: McGraw‐Hill.

Brittenham G (2004) Disorders of iron metabolism. In: Hoffman R, Benz EJ Jr Shattil SJ, et al. (eds) Hematology: Basic Principles and Practice, 4th edn. Philadelphia: Elsevier Science.

Huang SC and Benz EJ Jr (2003) Posttranscriptional factors influencing the hemoglobin content of the red cell. In: Steinberg M, Forget FG, Higgs DR, et al. (eds) Disorders of Hemoglobin, vol. 8, pp. 146–173. Cambridge, UK: Cambridge University Press.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Jr Benz, Edward J(Nov 2015) Iron‐Loading Anaemia. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0002272.pub2]