4th June 2025

Aetiology and epidemiology

Anaemia is defined as a low concentration of haemoglobin (Hb); it can be further categorised by mean cell volume (MCV) of the red blood cell (i.e. microcytic, normocytic or macrocytic) and each of these subtypes has their own aetiology. The skin manifestations of anaemia vary depending on the underlying cause. Approximately 33% of the population globally are thought to be anaemic.

Microcytic anaemia

• The most common cause of anaemia globally is iron-deficiency anaemia (IDA) – which is also by far the most common form of microcytic anaemia. 
• IDA is more common in low-income countries (reduced dietary iron intake, parasitic worm infections causing blood loss), young children (who require greater amounts of iron for growth) and pre-menopausal women (due to blood loss during menstruation).
• Other uncommon causes of microcytic anaemia include the thalassaemias (genetic diseases of abnormal Hb production, these are more common in people of Mediterranean, Middle-Eastern or Southeast Asian descent), and sideroblastic anaemia. When discussing microcytic anaemia in this topic, this will largely be referring to IDA.
• Aetiology
  • Reduced dietary intake of iron (poverty leading to malnutrition, meat-free diet)
  • Reduced absorption of iron (inflammatory bowel disease, coeliac disease, helicobacter pylori infection)
  • Bleeding (menstruation, gastrointestinal blood loss (malignancy, peptic ulcer disease, haemorrhoids), parasitic intestinal infections)

Normocytic anaemia

• The prevalence of normocytic anaemia increases with age; the most common form of normocytic anaemia is anaemia of chronic disease. Normocytic anaemia has been reported in up to 44% of men older than 85 years (in the USA).
• The causes of normocytic anaemia are numerous, including:
  • Anaemia of chronic disease
  • Acute blood loss
  • Bone marrow failure
  • Renal failure
  • Pregnancy

Macrocytic anaemia

• The most common cause of macrocytic anaemia is B12 and/or folate deficiency; this will produce a megaloblastic anaemia, where abnormal red blood cell precursors are found in the bone marrow.
• Macrocytic anaemia may also be non-megaloblastic.
• Megaloblastic macrocytic anaemia: causes of B12 and folate deficiency include:
  • Vegan diet (the main dietary sources of B12 are animal products such as meat, eggs, fish and dairy)
  • Pernicious anaemia (most frequently diagnosed aged 60, associated with other autoimmune conditions, F>M at a ratio of 1.6:1)
  • Disease of the terminal ileum (e.g. Crohn’s disease, tapeworm infection, small bowel bacterial overgrowth)
• Causes of a non-megaloblastic macrocytic anaemia:
  • Alcohol excess
  • Liver disease
  • Myelodysplastic syndromes
  • Hypothyroidism