8.2 - Haemolytic Anaemias Flashcards
what is the normal red blood cell lifespan
120 days
what is extravascular and intravascular haemolysis
abnormal breakdown (haemolysis) can occur in…
- blood vessels (intravascular haemolysis)
- spleen + wider reticuloendothelial system (extravascular haemolysis)
how is haemolytic anaemia caused
bone marrow can compensate for haemolysis by increasing production, but only up to a point. If haemolysis exceeds bone marrow capacity to compensate, then rate of destruction exceeds rate of production = anaemia
INHERITED - defective gene
* glycolysis defect eg pyruvate kinase deficiency
* pentose P pathway eg G6PDH deficiency
* membrane protein defect eg hereditary spherocytosis
* haemoglobin defect eg sickle cell
ACQUIRED - damage to cells
* mechanical damage, eg microangiopathic anaemia
* antibody damage eg autoimmune haemolytic anaemia
* oxidant damage eg exposure to chemicals or oxidants
* heat damage eg severe burns
* enzymatic damage eg snake venom
what are the key lab findings in a haemolytic anaemia
- raised reticulocytes, as the bone marrow is trying to compensate by increasing erythropoiesis
- raised bilirubin, as this is due to the breakdown of haem
- raised LDH (red cells are rich in this enzyme), and lots of red cells are being broken down
characteristic features of haemolytic anaemia
- severity of anaemia is generally worse than chronic disease if Hb is very low
- accumulation of bilirubin leading to jaundicc
- excess bilirubin can lead to increased risk of pigment gallstones (composed of bilirubin and calcium salts)
- overworking of red pulp leading to splenomegaly
- massive sudden haemolysis (eg due to incompatible blood transfusion) → cardiac arrest (to to lack fo O2 delivery) or hyperkalaemia (due to release of intracellular contents, can also cause arrythmia)
what are the three main defects in red cell membrane structure
details on seperate cards
- hereditary spherocytosis - cells take on spherical shape
- hereditary eliptocytosis - cells eliptical rather than bioconcave
- hereditary pyropoikilocytosis - abnormal sensitivity of red cells to heat
hereditary spherocytosis
- inherited defect in red cell membrane structure
- many cells take on spherical shape
- ankyrin, spectrin, protein 4.2 or band 3 defects
- these defects disrupt membrane-cytoskeletal interactions
- cells less deformable, so break down more easily in blood vessels and are removed by the spleen
hereditary eliptocytosis
- inherited defect in red cell membrane structure
- many cells are elliptical rather than bioconcave
- spectrin defect most common
- also defects in band 4.1, band 3 and glycophorin C proteins
- cells are less deformable so break down more easily in blood vessels and removed by the spleen
- severe form = hereditary pyropoikilocytosis (next card)
hereditary pyropoikilocytosis
- inherited defect in red cell membrane structure
- spectrin defect
- severe form of hereditary eliptocytosis
- abnormal sensitivity of red cells to heat
microangiopathic haemolytic anaemias
…result from mechanical damage eg
- shear stress as cells pass through defective heart valve (eg in aortic stenosis when cells forced through narrowed opening under high pressure)
- cells snagging on fibrin strands in small vessles where increased activation of clotting cascade has occured (eg in disseminated intravascular coagulation)
- heat damage from severe burns, as water moves out of cells
- osmotic damage eg where water enters cells (eg drowning in freshwater)
fragments resulting from mechanical damage are called schistocytes and are spiky and smaller than normal red blood cells
autoimmune haemolytic anaemias
- caused by autoantibodies binding to red cell membrane proteins
- can result form infections eg chest infection or lymphatic cancers
- classified as either warm (IgG) or cold (IgM) based on temperature antibodies react best at under lab conditions
- spleen recognises antibody bound cells as abnormal and removes them
- red cell lifespan reduced, resulting in anaemia
