Haemolysis Flashcards
Define haemolysis
Premature red cell destruction
Why are red cells particularly susceptible to damage?
Biconcave shape
Limited metabolic reserve (no mitochondria)
Can’t generate new proteins (no nucleus)
Define compensated haemolysis
Increased red cell destruction compensated by increased red cell production
Define decompensated haemolysis
Increased rate of red cell destruction exceeding bone marrow capacity for red cell production
What are the consequences of haemolysis?
Erythroid hyperplasia (increased bone marrow rbc production) Excess red cell breakdown products
What is the bone marrow response to haemolysis?
Reticulocytosis and erythroid hyperplasia
What is extravascular haemolysis?
Red cells are taken up by the reticuloendothelial system (mainly spleen and liver)
What is intravascular haemolysis?
Red cells destroyed within the circulation
What is the difference between extravascular and intravascular haemolysis?
Location, mechanism and breakdown products.
What is released during extravascular haemolysis and what is the result?
Protoporphyrin
Unconjugated bilirubinaemia, jaundice, gall stones, urobilinogenuria
What is the result of intravascular haemolysis?
Haemoglobinaemia
Methaemalbuminaemia
Haemoglobinuria (pink urine, turns black on standing)
Haemosiderinuria
What are the causes of intravascular haemolysis?
ABO incompatible blood transfusion
G6PD deficiency
Severe falciparum malaria
PNH/PCH
What investigations are used to confirm a haemolytic state?
FBC (blood film) Reticulocyte count Serum unconjugated bilirubin Serum haptoglobins Urinary urobilinogen
Investigations to identify the cause of a haemolytic state
History/examination: Genetic/acquired
Blood film: membrane damage (spherocytes)
Mechanical damage (rbc fragments)
Oxidative damage (heinz bodies)
Others (sickle cells)
Specialist investigations e.g. direct coombs test
How is haemolysis classified in terms of site of red cell defect?
Premature destruction of normal rbcs (autoimmune or mechanical)
Abnormal cell membrane
Abnormal red cell metabolism
Abnormal haemoglobin
Immune causes of haemolysis
Autoimmune, alloimmune
Causes of warm (IgG) haemolysis?
Idiopathic Autoimmune (SLE) Lymphoproliferative disorders (CLL) Drugs (penicillin) Infection
Causes of cold (IgM) haemolysis?
Idiopathic
Infection (EBV, mycoplasma)
Lymphoproliferative disorders
Causes of alloimmune haemolysis
Haemolytic transfusion reaction
Haemolytic disease of the newborn
Causes of mechanical red cell destruction.
DIC Haemolytic uraemic syndrome TTP Leaking heart valve Infection e.g. malaria
Causes of red cell membrane defects?
Liver disease
Vitamin E deficiency
Paroxysmal nocturnal haemoglobinuria
How are red cell membrane abnormalities caused?
Reduced membrane deformability
Increased transit time through spleen
Oxidant environment in spleen leads to extravascular red cell destruction
Hereditary spherocytosis
What condition causes abnormal red cell metabolism?
G6PD deficiency (failure to cope with oxidant stress)
What abnormalities does dapsone therapy lead to?
Keratocytes and abnormally contracted red cells
Name a genetic cause of haemolysis
Sickle cell anaemia
What causes sickle cell anaemia?
Point mutation in beta globin chain
