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Anaemia: pathophysiology, classification, and clinical features 

Anaemia: pathophysiology, classification, and clinical features

Anaemia: pathophysiology, classification, and clinical features

D.J. Weatherall

and Chris Hatton



Chapter reviewed December 2012—minor changes only.

Updated on 30 May 2013. The previous version of this content can be found here.
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date: 30 March 2017

Anaemia is usually defined clinically as a reduction of the haemoglobin concentration to less than 130 g/l (males) or less than 120 g/l (females). It is a common problem, with prevalence around 3% for middle-aged men and 14% for middle-aged women in the United Kingdom, and much greater prevalence in the developing world.

Adaptation to anaemia

Reduction in delivery of oxygen to the tissues triggers a variety of compensatory mechanisms, including (1) modulation of oxygen affinity—largely mediated by an increase in red blood cell 2,3-biphosphoglycerate; (2) increased production of erythropoietin—the main growth factor for red blood cell production; (3) redistribution of flow to benefit the myocardium, brain, and muscle; (4) increase in cardiac output; and (5) reduction of mixed venous oxygen tension to increase the arteriovenous oxygen difference.

Clinical manifestations

The clinical picture depends on whether anaemia is of rapid or insidious onset. Acute blood loss presents with features of intravascular volume depletion (see Chapter 17.3). Anaemia of gradual onset may (if mild) be asymptomatic or simply manifest as slight fatigue and pallor, or (if more severe) present with features including exertional dyspnoea, tachycardia, palpitations, angina, light-headedness, faintness, and signs of ‘cardiac failure’.

Causes and classification

Anaemia can be caused by the defective production of red cells or an increased rate of loss of cells, either by bleeding or premature destruction (haemolysis).

The causes of defective production of red cells include (1) deficiency of iron, vitamin B12 or folate; (2) anaemia of chronic disorders; (3) reduced erythropoietin production—chronic kidney disease; (4) primary diseases of the bone marrow.

Haemolytic anaemias—causes are (1) genetic—including membrane defects, haemoglobin disorders, and enzyme deficiencies; or (2) acquired—including autoimmune and nonimmune disorders.

Clinical approach

The key issues are to determine (1) the degree of disability caused by the anaemia and hence how quickly treatment must be started, a key question being ‘is blood transfusion required?’, and (2) cause of the anaemia.

The main causes of anaemia can be usefully classified according to the associated red cell changes: (1) hypochromic, microcytic—including iron deficiency (the commonest cause of anaemia), thalassaemia (common in some populations); (2) normochromic, macrocytic—vitamin B12 or folate deficiency, alcohol, myelodysplasia; (3) polychromatophilic, macrocytic—haemolysis; (4) normochromic, normocytic—chronic disorders, renal failure, diseases of the bone marrow; (5) leucoerythroblastic—myelofibrosis, leukaemia, metastatic carcinoma.

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