Haemolysis Flashcards
Define haemolysis
Premature red cell destruction - shortened survival
What makes red cells susceptible to haemolysis?
Shape
Limited metabolic reserve
Cannot generate new proteins
What is haemolytic anaemia?
Increased rate of red cell destruction exceeding bone marrow capacity causing Hb to fall
How does the bone marrow respond to haemolysis?
Reticulocytosis
Erythroid Hyperplasia
Describe reticulocytosis
Most immature red cells in the circulation, no nucleus but some RNA - polychromatic
What are the two types of haemolysis?
Extravascular
Intravascular
What is extravascular haemolysis?
Taken up by reticuloendothelial system - spleen and liver, hyperplasia occurs at site of destruction and there is release of normal products
What are the normal products released in extravascular haemolysis?
Protoporphyrin - unconjugated bilirubinaemia (jaundice and gallstones)
Urobilinogenuria
What happens in intravascular haemolysis?
Red cells destroyed within the circulation and spill their contents
Name the consequence of red cells spilling their contents
Haemoglobinaemia
Methaemalbumin
Haemoglobinuria (pink urine turns black on standing)
Haemosiderinuria (iron protein)
What can cause intravascular haemolysis?
ABO incompatibility G6PD deficiency Falciparum Malaria Paroxysmal cold haemoglobinuria Paroxysmal nocturnal haemoglobinuria
What investigations are done in suspected haemolysis?
FBC Blood film Reticulocyte count Serum unconjugated bilirubin and haptoglobin Urinary urobilinogen
What might be seen on a blood film of haemolysis?
Membrane damage - spherocytes
Mechanical damage - red cell fragments
Oxidative damage - Heinz bodies
HbS - sickle cell
Name the test used to detect red cell antibodies
Coomb’s Test
Name the four types of red cell defect
- premature destruction of normal red cell (immune or mechanical)
- abnormal cell membrane
- abnormal cell metabolism
- abnormal haemoglobin
What are the two types of immune mediated premature destruction?
Autoimmune
Alloimmune
Describe autoimmune haemolysis
Autoantibodies to red cells
Warm IgG
Cold IgM
What can cause warm IgG?
Idiopathic, autoimmune disorders, lymphoproliferative, infection, drugs
What can cause cold IgM?
Idiopathic, infections - EBV, mycoplasma, lymphoproliferative
What test can be used in Immune premature destruction?
Direct Coombs test
Name two types of alloimmune haemolysis
Haemolytic transfusion reaction
Haemolytic disease of the newborn
Name the causes of mechanical premature destruction
DIC, HUS, TTP, Malaria, leaky heart valve, burns
Why does red cell destruction happen in burns?
Red cells are sheared as they pass through the damaged capillaries - microspherocytes
Name three acquired membrane defects
Liver disease
Vitamin E deficiency
Paroxysmal nocturnal haemoglobinuria
What is the most common congenital membrane defect?
Hereditary spherocytosis
What happens in hereditary spherocytosis?
Reduced membrane deformability, increased transmit time through spleen, oxidant environment in spleen causes extravascular red cell destruction
What happens in G6PD deficiency?
Failure to cope with oxidant stress
Failure to generate ATP
Does there always have to be a G6PD deficiency for abnormal red cell metabolism to occur?
No - can occur due to increase oxidative stress due to drugs e.g. Dapsone
Describe the pathology of oxidation
Denatured Hb forms inclusion (Heinz bodies), this causes the spleen to take ‘bites’ out of the cell in an effort to remove them and thus forms irregular contracted cells and keratocytes
What is the most common haemoglobinopathy to cause haemolysis?
Sickle cell
