Anaemia Flashcards
What is anaemia
Reduction in the amount of haemoglobin in a given volume of blood below what would be expected in comparison with a healthy subject of the same age and gender
What in a FBC is reduced in anaemia
Hb
Usually RBC and Hct
What may anaemia be a result of
Reduction in the absolute amount of haemoglobin in the blood stream
Occasionally due to an increase in volume plasma (cannot persist as excess fluid is excreted)
What are the mechanisms of anaemia
Reduced production of red cells/haemoglobin in the bone marrow
Loss of blood from the body
Reduced survival of red cells in the circulation
Pooling of red cells in a very large spleen
What are the causes of microcytic anaemia
Defect in haem synthesis
- iron deficiency
- anaemia of chronic disease
Defect in global synthesis (thalassaemia)
- Defect in α chain synthesis
- Defect in β chain synthesis
Describe macrocytic anaemia
Average cell size is increased
Usually result from abnormal haemopoiesis
The red cell precursors continue to synthesise haemoglobin and other cellular proteins but fail to divide normally
May be due to premature release of cells from bone marrow (20% larger)
What is megaloblastic erythropoiesis
A cause of macrocytic anaemia
Delay in maturation of the nucleus while the cytoplasm continues to mature and the cell continues to grow
What is a megaloblast
Abnormal bone marrow erythroblast
Larger than normal and shows nuclei-cytoplasmic dissociation
What are the common causes of macrocytic anaemia
Megaloblastic anaemia as a result of lack of vitamin B12 or folic acid
Use of drugs interfering with DNA synthesis
Liver disease and ethanol toxicity
Recent major blood loss with adequate iron stores (increased reticulocytes)
Haemolytic anaemia (increased reticulocytes)
What are the mechanisms of normocytic anaemia
Recent blood loss
Failure of production of red cells
Pooling of red cells in the spleen
What are the causes of normocytic normochromic anaemia
Peptic ulcer, oesophageal varices, trauma
Failure of production of red cells
Hypersplenism e.g. portal cirrhosis
Describe haemolytic anaemia
Resulting from shortened survival of red cells in the circulation
May be due to intrinsic abnormality of the red cells or extrinsic factors acting on normal red cells
What is the difference between inherited and acquired haemolytic anaemia
Inherited - can result from abnormalities in the cell membrane, haemoglobin or enzymes in the red cell
Acquired - usually results from extrinsic factors such as micro-organisms, chemicals or drugs that damage the red cell
What is the difference between intravascular and extravascular haemolysis
Haemolysis is partly intravascular and partly extravascular
Intravascular - if there is very acute damage to the red cell
Extravascular - Defective red cells are removed by the spleen
Give examples of causes of inherited haemolytic anaemia
Cell membrane - Hereditary spherocytosis
Haemoglobin - Sickle cell
Glycolytic pathway - pyruvate kinase deficiency
Enzymes of pentose shunt - G6PD deficiency
Give examples of causes of acquired haemolytic anaemia
Cell membrane - Autoimmune haemolytic anaemia or snake bite
Whole cell - Microangiopathic haemolytic anaemia, malaria
Oxidant exposure - damson or primaquine
How may acquire haemolytic anaemia cause inherited anaemia
Precipitation of episodic haemolysis in individuals with an enzyme deficiency (from oxidant exposure damage) can cause a defect in enzymes of the pentose shunt
When should haemolytic anaemia be expected
Otherwise unexplained anaemia (normochromic and normocytic/macrocytic)
Evidence of morphologically abnormal red cells
Evidence of increased red cell breakdown
Evidence of increased bone marrow activity
Describe hereditary spherocytosis
Haemolytic anaemia or chronic compensated haemolysis resulting from an inherited intrinsic defect of the red cell membrane
After entering the circulation the cells lose membrane in the spleen and thus become spherocytic
How does hereditary spherocytosis lead to jaundice
Spherocytes are less flexible and are removed prematurely by the spleen (extravascular haemolysis)
The bone marrow responds nay increasing output of red cells, leading to polychromasia and reticulocytosis
Leads to increased bilirubin production, jaundice and gall stones
What is the osmotic fragility test
Spherocytes are more prone to haemolyse when osmotic pressure is reduced
How is hereditary spherocytosis treated
Splenectomy
Good diet so secondary folic acid deficiency does not occur
One folic acid tablet taken daily
Describe glucose-6-phosphate dehydrogenase deficiency
G6PD is an important enzyme in the pentose phosphate shunt
Essential for the protection of the red cell from oxidant damage
Gene for G6PD is on the X chromosome so those affected are usually homozygous males (sometimes homozygous females)
What causes oxidant damage
Oxidants may be generated in the blood stream e.g. during infection, or may be exogenous
extrinsic - broad beans
intrinsic - naphthalene in mothballs
Drugs - dapsone, primaquine
What does G6PD deficiency cause
Intermittent severe intravascular haemolysis as a result of infection or exposure to an exogenous oxidant
Such episodes are associated with irregularly contracted cells
Haemoglobin is denatured and forms Heinz bodies (round inclusions)
Describe autoimmune haemolytic anaemia
Results from production of autoantibodies directed at red cell antigens
Immunoglobulins bound to red cell membrane is recognised by splenic macrophages, which removes parts of the red cell membrane -> spherocytosis
Complements can be bound to the Ig molecule and recognised by splenic macrophages
How does autoimmune haemolytic anaemia -
Spherocytes are less flexible
Combination of cell rigidity and recognition of antibody and complement on the red cell surface by splenic macrophages leads to removal of cells by the spleen
How is autoimmune haemolytic anaemia diagnosed
Spherocytes found
Increased reticulocyte count
Immunoglobulin and complement on red cell surface detected
Antibodies to red cell antigens or other autoantibodies in the plasma detected
How is autoimmune haemolytic anaemia treated
use of corticosteroids and other immunosuppressive agents
Splenectomy for severe cases
How is microangiopathic haemolytic anaemia treated
Remove the cause e.g. treat hypertension or stopping a causative drug
Plasma exchange when it is caused by an antibody in the plasma that is leading indirectly to fibrin deposition
What can cause failure of production of red cells
- Early stages of iron deficiency or anaemia of chronic disease
- renal failure
- bone marrow failure or suppression
- bone marrow infiltration
