Week 1- Haemolysis Flashcards
What is heamolysis?
Premature red cell destruction (shortened red cell lifespan)
Why are red cells particularly susceptible to damage?
They have to maintain their biconcave shape to maintain affective
They have limited metabolic reserve and rely solely on glucose metabolism for energy (no mitochondria)
Cant generate new proteins once in the circulation (no nucleus)
NOTE
Not everyone who has haemolysis is anaemic.
What is compensated haemolysis?
Increased red cell destruction compensated by increased red cell production. Therefore Hb is maintained.
What is haemolytic anaemia?
Increased rate of red cell destruction exceeding bone marrow capacity for red cell production. Therefore Hb falls.
What are some consequences of haemolysis?
Erythroid hyperplasia (hyperplasia of the erythron- the area of the bone marrow responsible for red cell production). This would show increased reticulocytes. Excess red cell breakdown products e.g. bilirubin
NOTE
It is really difficult to measure red cell survival rate, so you have to measure it in round about ways.
What is the bone marrows response to haemolysis?
Reticulocytosis
Erythroid hyperplasia
What will a blood film in a patient with haemolysis show?
Polychromatic (due to high number of reticulocytes).
How can haemolysis be classified?
Classified in regards to site of red cell destruction- extravascular or intravascular.
How can haemolysis be classified?
Classified in regards to site of red cell destruction- extravascular or intravascular.
Can also be classified by site of red cell defect.
Where does intravascular haemolysis occur?
Red cells are destroyed within the circulation.
Which type of haemolysis is more common?
Extravascular
What signs point you towards thinking its an extravascular cause rather than an intravascular cause?
Splenomegaly +/- hepatomegaly- organs get bigger because they are doing more work.
Release of protoporthyrin- broken down to make bilirubin causing jaundice, gallstones, urobilinogenuria
What signs point you towards thinking its an extravascular cause rather than an intravascular cause?
Splenomegaly +/- hepatomegaly- organs get bigger because they are doing more work.
Release of protoporthyrin- broken down to make bilirubin causing jaundice, gallstones, urobilinogenuria
These are all normal products but in excess.
What signs point you towards thinking it is an intravascular cause rather than an extravascular cause?
In intravascular haemolysis, the contents spill out into the circulation. This means you get:
Haemoglobinaemia (free Hb in the circulation)
Methaemalbuminaemia- this is Hb bound to albumin
Haemoglobinuria- hb secreted directly into urine (pink colour) and if its left to stand it will turn black
Haemosiderinuria- iron containing products in the urine.
These are all abnormal products that you wouldn’t expect to see.
What scenarios might you get an intravascular haemolysis occurring?
ABO incompatible blood transfusion
G6PD deficiency
Severe falciparum malaria (blackwater fever- urine goes black as Hb is released into the urine)
Which blood investigations would you do into haemolysis?
Start by confirming haemolytic state
FBC (and blood film)- just because they aren’t anaemic doesn’t mean they aren’t haemolysing
Reticulocyte count- to assess bone marrow response
Serum unconjugated bilirubin- Main breakdown product
Serum haptoglobins- what binds haemoglobin in the circulation. If this is low its generally a sensitive test for Hb being low
Urinary urobilinogen- breakdown product of bilirubin.
What may a blood film show which indicate you towards a a cause of haemolysis?
Spherocytes- sickle cell anaemia or hereditary spherocytosis
Mechanical damage- red cell fragments
Oxidative damage- Heinz bodys
Others e.g. sickle cells
Another way to classify is by site of red cell defect, outline where can the red cell defects could be?
Can be 1-premature destruction of normal red cells (autoimmune or mechanical) 2-abnormal cell membrane 3-abnormal red cell metabolism 4-abnormal haemoglobin
What is meant by autoimmune destruction?
Patients own antibodies are destroying the red cells.
What is meant by alloimmune destruction?
foreign antibodies are destroying the patients red cells.
How can autoimmune haemolysis be classified?
Can either be IgG (warm) or IgM (cold) causes.
Which type of autoimmune haemolysis is most common?
IgG is most common.
Name some causes of IgG mediated autoimmune haemolysis?
Most often it is idiopathic Can sometimes be associated with autoimmune disorders e.g. SLE Lymphoproliferative disorders Drugs e.g. penicillin Infection
Name some causes of IgM mediated autoimmune haemoylsis?
Idiopathic
Infections (EBV, mycoplasma)
Lymphoproliferative disorders
Which test would you use to diagnose an IgG cause of haemolysis? Describe this test?
Direct Coombs test
Add anti-human IgG to the red cells (that are coated in their IgG) and they will agglutinate.
If no IgG is present- no agglutination will occur.
What can cause alloimmune haemolysis?
An immune response to blood transfusions. This can be immediate which is IgM mediated, or delayed which is IgG mediated (this is usually extravascular).
Or passive transfer of antibody e.g. haemolytic disease of the newborn due to ABO or Rh(D) mismatch between mother and child.
What mechanical causes of red cell destruction can occur to cause haemolysis?
Disseminated intravascular coagulation Haemolytic uraemic syndrome Thrombotic thrombocytopenic purpura Leaking heart valve (red cells get churned up going through leading to haemolysis) Infection- particularly malaria Burns victims
What can cause abnormal cell membrane defects in RBC’s causing haemolysis?
Acquired These are all very rare Occasionally patients with severe chronic liver disease (Zeives syndrome) Vitamin E deficiency Paraoxysmal nocturnal haemoglobinuria
Or congenital
Hereditary spherocytosis
What can cause abnormal red cell metabolism?
G6PD deficiency- causes the red cells to have an inability to deal with oxidative stress.
Some drugs- e.g. dapsone as it can overload antioxidant protective pathways.
What congenital causes of abnormal haemoglobin can cause red cell haemolysis?
Sickle cell disease
