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 (ASH) 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. A series of differentiation steps results in the generation of 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.
At steady state, the rate of RBC production equals the rate of RBC loss. Anaemia develops when the rate of RBC production decreases and/or the rate of RBC 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]); further 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]); further 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 (GI) bleeding
- Rupture of a vascular aneurysm
- Iron deficiency
- Vitamin B12 deficiency
- Folate deficiency
- Myelodysplastic syndrome
- Acute lymphocytic leukaemia
- Acute myelogenous leukaemia
- Chronic myelogenous 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 abuse
- Lead toxicity
- Autoimmune haemolytic anaemia (AIHA)
- 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
Baptist MD Anderson Cancer Center
RZ declares that he has no competing interests.
Dr Robert Zaiden would like to gratefully acknowledge Dr Fauzia Rana, a previous contributor to this topic.
FR declares that she has no competing interests.
Associate Professor of Medicine
Innsbruck Medical University
CP declares that he has no competing interests.
Associate Professor of Clinical Medicine
Department of Medicine
Division of Hematology/Oncology
University of Virginia
JD declares that he has no competing interests.
Internal Medicine Instructor
Member of Evidence Based Medicine Unit
Catholic University of Chile
CA declares that he has no competing interests.
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