Anaemia: Overview

Abstract

Anaemia, a decrease in erythrocyte mass that is reflected in a reduction in the haemoglobin concentration in the peripheral blood, is the most common haematologic condition for which medical attention is sought. Erythrocytes are critical to tissue oxygenation and carbon dioxide removal, and severe anaemia may lead to tissue hypoxia and organ dysfunction. Erythropoiesis is a highly regulated process controlled by erythropoietin. Adaptive mechanisms permit moderate anaemia to be well tolerated, and the clinical importance of mild to moderate anaemia is its representation of an underlying disease. Mild to moderate anaemia may be one of the first clues of an underlying disease. Although many of the signs and symptoms of anaemia are nonspecific, a pragmatic classification of anaemia based on integration of kinetic and morphologic characteristics of erythrocytes allows efficient investigation of the underlying aetiology.

Key Concepts

  • Anaemia is the most common haematologic condition encountered in medical practice
  • Erythrocytes are critical to tissue oxygenation and carbon dioxide removal
  • Physiologic compensatory mechanisms allow mild to moderate anaemia to be well tolerated; severe anaemia may be associated with tissue hypoxia and organ dysfunction
  • Erythropoiesis, the production of erythrocytes, is a tightly regulated process controlled predominantly by the synthesis of erythropoietin in response to hypoxia
  • The clinical significance of mild–moderate anaemia lies in its association with an underlying systemic disease; the finding of anaemia should prompt consideration of additional investigations
  • Classification of anaemia based on kinetic and morphologic erythrocyte characteristics allows pragmatic segregation into microcytic, macrocytic or normocytic anaemia, further directing the investigation of an underlying disease

Keywords: erythrocyte; anaemia; haemoglobin; oxygen delivery; erythropoiesis; systemic disease; adaptation; microcytic; normocytic; macrocytic

Figure 1. Haematopoiesis is a process, whereby haematopoietic stem cells differentiate into erythroid precursors, which then mature into erythrocytes. Maturation of erythrocyte precursors is regulated by growth and transcription factors. Erythropoietin (EPO) functions to drive the survival and proliferation of committed erythroid progenitors in the marrow. Reproduced with permission from Israels LG and Israels SG 2002 © Core Health Services Inc.
Figure 2. Control of erythropoietin synthesis. Erythropoietin (EPO) synthesis is induced by subtle decreases in oxygen delivery (hypoxia) as sensed by the kidney. Hypoxia stimulates stabilisation of the hypoxia‐inducible factors (HIF), which then binds to the hypoxia‐responsive element (HRE) on the erythropoietin gene, and results in increased synthesis of EPO and other factors important to oxygen homeostasis. Reproduced with permission from Israels LG and Israels SG 2002 © Core Health Services Inc.
Figure 3. A diagnostic algorithm for anaemia. Classification of anaemia based on kinetic and morphologic erythrocyte characteristics allows pragmatic segregation into microcytic, macrocytic or normocytic anaemia, further directing investigation of underlying disease to arrive at a specific diagnosis. Classification of micro‐, macro‐ and normocytosis is based on the size of individual erythrocytes. The degree of reticulocytosis defines the anaemia as hypoproliferative or hyperproliferative. MCV, mean corpuscular volume; ESR, erythrocyte sedimentation rate; CRP, C‐reactive protein; B12, vitamin B12 (cobalamin); LFTs, liver function tests; SPEP, serum protein electrophoresis; FLCR, free light chain ratio; LDH, lactate dehydrogenase; N or norm, normal; abn, abnormal; G‐6‐PD, glucose‐6‐phosphate dehydrogenase; PK, protein kinase; retic, reticulocyte count.
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References

DeLoughery TG (2014) Microcytic anemia. New England Journal of Medicine 371: 1324–1331.

Dhaliwal G, Cornett PA and Tierney LM (2004) Hemolytic anemia. American Family Physician 69 (11): 2599–2607.

Ganz T and Nemeth E (2011) Hepcidin and disorders of iron metabolism. Annual Reviews of Medicine 62: 347–360.

Israels LG and Israels SG (2002) Erythropoiesis: The red cell, heme synthesis, porphyrin metabolism and iron metabolism. In: Israels SJ (ed) Mechanisms in Hematology, 3rd edn. Ontario: Core Health Services Inc..

Kaushansky K and Williams WJ (2010) Williams Hematology, 8th edn. New York: McGraw‐Hill Medical.

McDermid JM, Jaye A, Schim van der Loeff MF, et al. (2007) Elevated iron status strongly predicts mortality in West African adults with HIV infection. Journal of Acquired Immune Deficiency Syndromes 46 (4): 498–507.

Sazawal S, Black RE, Ramsan M, et al. (2006) Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community‐based, randomised, placebo‐controlled trial. Lancet 367 (9505): 133–143. DOI: 10.1016/S0140-6736(06)67962-2.

Stabler SP (2013) Vitamin B12 deficiency. New England Journal of Medicine 368: 149–160.

Wakeman L and Munroe R (2007) Robust, routine haematology reference ranges for healthy adults. International Journal of Laboratory Hematology 29: 279–283.

Watkins DR and Rosenblatt DS (2015) Vitamin B12 and folate metabolism. In: Israels S and Israels ED (eds) Mechanisms in Hematology, 4th edn. Concord: Core Health Services, Inc.

Weiskopf RB, Viele MK, Feiner J, et al. (1998) Human cardiovascular and metabolic response to acute, severe isovolemic anemia. JAMA 279 (3): 217–221.

Weiss G and Goodnough LT (2005) Anemia of chronic disease. New England Journal of Medicine 352 (10): 1011–1023. DOI: 10.1056/NEJMra041809.

Zarychanski R and Houston DS (2008) Anemia of chronic disease: a harmful disorder or an adaptive, beneficial response? CMAJ 179 (4): 333–337. DOI: 10.1503/cmaj.071131.

Zimmermann MB and Hurrell RF (2007) Nutritional iron deficiency. Lancet 370 (9586): 511–520. DOI: 10.1016/S0140-6736(07)61235-5.

Further Reading

Hoffbrand AV and Moss PAH (2011) Essential Hematology, 6th edn. Chichester, Weset Sussex: Wiley Blackwell.

Israels LG and Israels SG (2002) Mechanisms in Hematology, 3rd edn. Core Health Services Inc: Ontario.

Kaushansky K and Williams WJ (2010) Williams Hematology, 8th edn. New York: McGraw‐Hill Medical.

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Houston, Brett L, Houston, Donald S, and Zarychanski, Ryan(Jul 2015) Anaemia: Overview. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0002156.pub2]