Anaemia
Pathophysiology
The normal range of haemoglobin varies depending on sex, age and different hospital laboratories. Females have a lower haemoglobin than males due to menstrual loss, and during pregnancy.
Anaemia is a condition characterised as a reduction in the haemoglobin concentration. This reduces the ability of the red blood cell to carry oxygen around the body.
Clinical Features
Causes of Anaemia
The causes of anaemia can be classified by the size of the red blood cell: Macrocytic (large red cell), Normocytic (normal sized red cell) and Microcytic (small red cell).
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Macrocytic Anaemia
Megaloblastic anaemias: B12 and folate deficiency
Vitamin B12 and folic acid are important for DNA synthesis. In B12 and folate deficiency, RNA synthesis still occurs, which allows the cytoplasm to keep growing in size, whereas nuclear division can not occur if DNA synthesis is ineffective, resulting in red blood cells with large cytoplasms, called “megaloblasts” seen in the bone marrow.2,3 Visit the Megaloblastic Anaemias page for more detailed information (causes, clinical features, investigations, management).
If both are deficient, B12 levels should be corrected first, as B12 is required for the activation of folate.
Alcoholism and Liver Disease
Toxic effects of alcohol can directly affect the bone marrow and therefore the red blood cell production. It can also indirectly affect absorption of nutrients eg folate which will affect red blood cells and cause anaemia. 2
Impaired Red Cell Production in the Bone Marrow
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Aplastic anaemia - failure of bone marrow
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Autoimmune disease of the bone marrow
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Most cases are idiopathic
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Can be caused by viruses eg Hep B, cytotoxic drugs or radiation, reaction to drugs
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Treatment - bone marrow transplant, immunosuppresive agents (ex. Alemtuzumab, Anti-Thymocyte Globulin), supportive transfusions (platelets, red blood cells)
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Myelodysplasia - ineffective red cell production
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Group of conditions that may be pre-leukaemic
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Hypothyroidism
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Thyroid hormones can affect erythropoietin and can therefore stimulate the growth of red blood cells.2
Haemolytic Anaemias
Haemolytic anaemia causes are either hereditary or acquired.
Hereditary causes can be further divided into whether stimulus lies outside, within or inside red cell membrane. Acquried causes can be classified into mechanical causes of damage to RBCs, immune-mediated damage, and drug-induced damage. The diagram summaries the causes. Visit the Haemolytic Anaemias page for more detailed information.
Normocytic Anaemia
Anaemia of Chronic Disease
Any condition causing chronic inflammation can prevent the body from utilising iron efficiently leading to decreased number of red cells. Examples of chronic conditions are rheumatoid arthritis, tuberculosis, malignancies.
Acute blood loss
Acute blood loss can be due to a major trauma or internal bleeding that will cause normocytic, normochromic (normal levels of haemoglobin) anaemia. In the acute setting, iron is still available for RBC synthesis to occur as normal, so the size of the red blood cells will still be normal.
Mixed deficiency anaemia
Different causes of anaemia may exist in a patient - a microcytic and macrocytic anaemia would result in an ioveral normocytic reading. For example a patient may have both iron deficiency and B12/folate deficiency.
Bone marrow failure/ineffective erythropoiesis
Marrow failure can occur in patients with bone marrow malignancy (eg leukaemia or myelofibrosis), post chemotherapy, or have chronic renal disease resulting in decreased erythropoietin.
Microcytic Anaemia
Iron Deficiency Anaemia (IDA)
IDA is a symptom most likely caused by dietary deficiency or chronic blood loss which may be due to heavy menstrual bleeding (menorrhagia) or blood loss from gastrointestinal tract. It causes a microcytic hypochromic anaemia, confirmed by low iron levels and raised Total Iron Binding Capacity (TIBC) on haematinic studies.
Management of insufficient dietary intake includes dietary advice (red meats, leafy greens), and oral ferrous sulphage. For all other causes, anaemia is managed by treatment of the underlying problem.
Sickle Cell Disease
Sickle cell disease is an autosomal reccessive haemoglobinopathy. The abnormal haemoglobin causes the red blood cells to sickle, creating smaller red blood cells. For detailed information on this condition, visit our Sickle Cell Disease page.
Thalassaemia
Thalassaemias are inherited haemoglobinopathies. In this condition, haemoglobin is missing either alpha or beta chains, impairing RBC synthesis. For detailed information on this condition, visit our Thalassaemia page.
Investigations for Anaemias
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Full Blood Count
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Haemoglobin - to confirm whether the patient has anaemia
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Mean Cell Volume (MCV) - confirm whether anaemia is macrocytic, normocytic or microcytic
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If microcytic:
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Ferritin levels and transferrin saturation (TSAT)
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If normocytic:
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Ferritin levels and transferrin saturation (TSAT)
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Renal and liver function tests
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C-reactive protein (CRP)/ Erythrocyte sedimentation rate (ESR) - markers of inflammation
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If macrocytic:
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B12 and folate levels
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LFT, Thyroid Function Tests (TFT)
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Reticulocyte count
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References
1. Mehta AB, Hoffbrand AV. Haematology at a Glance. 4th ed.: John Wiley & Sons; 2014.
2. Nagao T, Hirokawa M. Diagnosis and treatment of macrocytic anemias in adults. Journal of General and Family Medicine. 2017;18(5):200-204.
3. Castellanos-Sinco H, Ramos-Peñafie C, Santoyo-Sánchez A, Collazo-Jaloma J, Martínez-Murillo C, Montaño-Figueroa E et al. Megaloblastic anaemia: Folic acid and vitamin B12 metabolism. Revista Médica del Hospital General de México. 2015;78(3):135-143.