Anaemia is a haemoglobin (Hb) level two standard deviations below the mean for the age and sex of the patient. Reference ranges vary between laboratories. The World Health Organization defines anaemia as:
Hb <11 g/dL in children under 5 years and in pregnant women
Hb <11.5 g/dL in children aged 5 to 11 years
Hb <12 g/dL in children aged 12 to 14 years and in women (aged over 15 years)
Hb <13 g/dL in men (aged over 15 years)
The American Society of Hematology defines anaemia as <13.5 g/dL in men and <12 g/dL in women.
Anaemia is the most common haematological disorder seen in general medical practice. Risk factors include extremes of age, female sex, lactation, and pregnancy. The most common cause internationally is iron deficiency.
Anaemia can cause significant morbidity if left untreated, and is often the presenting sign of a more serious underlying condition. The rate at which anaemia develops is often as important as the severity, as a rapid decline can overwhelm the compensatory mechanisms of the body.
Erythropoiesis takes place within the bone marrow and is controlled by the stromal network, cytokines, and the hormone erythropoietin. Through a series of differentiation steps, haematopoietic stem cells become reticulocytes (red blood cells [RBCs] with an intact ribosomal network).
Reticulocytes remain in the bone marrow for 3 days before being released into the circulation. After one further day in the circulation, reticulocytes lose their ribosomal network and become mature RBCs, which circulate for 110-120 days before being removed from the circulation by macrophages.
Anaemia develops when the rate of red blood cell production decreases and/or the rate of red blood cell loss increases.
Morphological classification of anaemia
The most clinically useful classification system is based on the mean corpuscular volume (MCV).
Microcytic (MCV <80 femtolitres [fL]).
Normocytic (MCV 80-100 femtolitres [fL]); subclassified according to the reticulocyte count as:
Hyperproliferative (reticulocyte count >2%): the proportion of circulating reticulocytes increases as part of a compensatory response to increased destruction or loss of RBCs. The cause is usually acute blood loss or haemolysis.
Hypoproliferative (reticulocyte count <2%): these are primarily disorders of decreased RBC production, and the proportion of circulating reticulocytes remains unchanged.
Macrocytic (MCV >100 femtolitres [fL]); subclassified as:
Megaloblastic: a deficiency of DNA production or maturation resulting in the appearance of large immature RBCs (megaloblasts) and hypersegmented neutrophils in the circulation.
Non-megaloblastic: encompasses all other causes of macrocytic anaemia in which DNA synthesis is normal. Megaloblasts and hypersegmented neutrophils are absent.
- Acute gastrointestinal bleeding
- Rupture of a vascular aneurysm
- Iron deficiency
- Vitamin B12 deficiency
- Folate deficiency
- Myelodysplastic syndrome
- Acute lymphocytic leukaemia
- Acute myeloid leukaemia
- Chronic myeloid leukaemia
- Hairy cell leukaemia
- Acquired aplastic anaemia
- Infiltration by secondary malignancy
- Pure red cell aplasia
- Drug toxicity
- Anaemia of chronic disease
- Chronic kidney disease
- Chronic liver disease
- Generalised malnutrition
- Cytotoxic chemotherapy
- Alcohol misuse
- Lead toxicity
- Autoimmune haemolytic anaemia
- Transfusion reaction
- Viral hepatitis
- Parvovirus B19 infection
- Infectious mononucleosis
- Cytomegalovirus (CMV)
- Sickle cell anaemia
- Hereditary spherocytosis
- Glucose-6-phosphate dehydrogenase deficiency (G6PD)
- Bone marrow failure syndromes
- Haemolytic uraemic syndrome
- Disseminated intravascular coagulation (DIC)
- Thrombotic thrombocytopenic purpura
- Malignant hypertension
- Prosthetic valves and surfaces
- Cutaneous burns
- WHO guideline on use of ferritin concentrations to assess iron status in individuals and populations
- Guidelines on the management of drug-induced immune and secondary autoimmune, haemolytic anaemia
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