Haemolysis Flashcards
what is it?
Premature red cell destruction – shortened red cell survival
types of haemolysis
extravascular - taken up by reticuloendothelial system (spleen and liver predominantly)
intravascular - red cells destroyed in circulation
different mechanisms therefore different breakdown products detected
useful classification as knowing intra/extravascular haemolysis helps determine the cause of haemolysis
properties of extravascular haemolysis?
Commoner, hyperplasia at site of destruction (splenomegaly or hepatomegaly)
Release of protoporphyrin – unconjugated bilirubinaemia, jaundice, gall stones, Urobilinogenuria
Normal products in excess
properties of intravascular haemolysis?
Red cells are destroyed in the circulation spilling their contents
- Haemoglobinaemia (free Hb in circulation)
- Methaemalbuminaemia
- Haemoglobinuria: pink urine, turns black on standing
- Haemosiderinuria
- Abnormal products
Intravascular haemolysis may be life threatening
why are rbc susceptible to damage?
- They need to have a biconcave shape to transit the circulation successfully
- They have limited metabolic reserve and rely exclusively on glucose metabolism for energy (no mitochondria)
- Can’t generate new proteins once in the circulation (no nucleus)
what are the consequences of haemolysis?
- Erythroid hyperplasia (increased bone marrow red cell production)
- Excess red cell breakdown products e.g. bilirubin (clinical features differ y aetiology and site of red cell breakdown)
how is haemolysis diagnosed?
Not possible to directly measure red cell survival routinely
Rely on detecting the consequences of haemolysis and the investigating the cause
o Increased red cell production
o Detection of breakdown products – specific products help determine cause
what is compensated haemolysis?
Increased red cell destruction compensated by increased red cell production – Hb maintained
how is haemolysis investigated?
confirm haemolytic state
identify cause
what tests confirm a haemolytic state?
o FBC (+blood film) o Reticulocyte count o Serum unconjugated bilirubin o Serum haptoglobins o Urinary urobilinogen
how are the causes of a haemolytic state found?
o History and examination – family history, organomegaly
o Blood film
- Membrane damage (spherocytes)
- Mechanical damage (red cell fragments)
- Oxidative damage (Heinz bodies)
o Specialist investigations (direct coomb’s test and others)
immune causes of haemolysis
Autoimmune haemolysis o Warm or cold autoantibody o Warm (IgG) idiopathic (commonest) - Autoimmune disorders (SLE) - Lymphoproliferative disorders (CLL) - Drugs (penicillins etc.) - Infections o Cold (IgM) - Idiopathic - Infections (EBV, mycoplasma) - Lymphoproliferative disorders o Direct coombs’ test – identifies antibody (and complement) bound to own red cells
Alloimmune haemolysis o Immune response (antibody produced) o Haemolytic transfusion reaction - Immediate (IgM) predominantly intravascular - Delayed (IgG) predominantly extravascular o Passive transfer of antibody o Haemolytic disease of the newborn - Rh D - ABO incompatibility - Others eg anti-Kell
mechanical red cell destruction
o Disseminated intravascular coagulation o Haemolytic uraemic syndrome (eg E. coli O157) o TTP o Leaking heart valve o Infections e.g. Malaria
o Mechanical valve related – microangiopathic haemolytic anaemia (MAHA)
- Red cell fragmentation as a result of mechanical (extrinsic) damage
o Burns related haemolysis
- Microspherocytes, red cells are sheared as they pass through the damaged capillaries. Only seen therefore in severe burns
acquired causes of abnormal cell membrane (all very rare)
o Liver disease (zieve’s syndrome)
o Vitamin E deficiency
o Paroxysmal nocturnal haemoglobinuria – rare cause of haemolysis but an interesting acquired molecular defect
genetic red cell membrane abnormalities
o Reduced membrane deformability
o Increased transit time through spleen
o Oxidant environment in spleen causes extravascular red cell destruction
o Hereditary spherocytosis
