Anaemia is defined as a haemoglobin (Hb) level <120g/L (<12 g/dL) in females and <140g/L (<14 g/dL) in males, or as a Hb level <125g/L (<12.5 g/dL) in adults.    It is the most common haematological disorder seen in general medical practice. Risk factors include extremes of age, female gender, 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 (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 to 120 days before being removed from the circulation by macrophages. At steady state, the rate of RBC production equals the rate of RBC loss.
Haemolytic anaemias are a group of anaemias produced by increased destruction of RBCs with a resultant increase in circulating indirect bilirubin.   Clinical jaundice appears once bilirubin levels rise above 34.2 to 68.4 mmol/L (2-4 mg/dL). Additional disease-specific symptoms may also be present. The resulting anaemia can be microcytic or hyperproliferative normocytic, depending on the cause.
Microangiopathic haemolytic anaemias are often considered as a group. They produce a hyperproliferative normocytic anaemia. The underlying disease process produces endothelial damage and activates the coagulation cascade, leading to fibrin deposition on the damaged endothelial surfaces. In small vessels, the endothelial fibrin causes mechanical fragmentation and shearing of RBCs, leading to haemolysis. The irregular-shaped RBC fragments produced by this process are called schistocytes and can be seen on a peripheral blood smear.
Morphological classification of anaemia
Microcytic (MCV <80 fL). View image
Normocytic (MCV 80-100 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 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. View image
Non-megaloblastic: encompasses all other causes of macrocytic anaemia in which DNA synthesis is normal. Megaloblasts and hypersegmented neutrophils are absent.
- Acute GI bleeding
- Rupture of a vascular aneurysm
- Iron deficiency
- Vitamin B12 deficiency
- Folate deficiency
- Myelodysplastic syndrome
- Acute lymphocytic leukemia
- Acute myelogenous leukemia
- Chronic myelogenous leukemia
- Hairy cell leukemia
- Acquired aplastic anaemia
- Infiltration by secondary malignancy
- Pure red cell aplasia
- Drug toxicity
- Anaemia of chronic disease
- Chronic renal failure
- 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