Haemolysis Flashcards
What is haemolysis?
Premature red cell destruction
What products of red cell breakdown are a) recycled? b) broken down?
a) iron and globin chains b) haem group (protoporphyrin)
The haem group is first broken down into what? And then into what? For this reason, the first sign of somebody who is haemolysing may be what?
Biliverdin / bilirubin / they become jaundiced
What are the two main consequences of haemolysis?
Erythroid hyperplasia (more red cell production in the bone marrow) and presence of excess red cell breakdown products
What is compensated haemolysis?
When there is increased red cell destruction which is compensated for by increased red cell production
What happens to Hb in compensated haemolysis? Do patients become anaemic?
It is normal / no
What is decompensated haemolysis?
Increased rate of red cell destruction exceeds the bone marrow capacity for red cell production
What happens to Hb in decompensated haemolysis? Do patients become anaemia?
It is low / yes
It is difficult to measure red cell survival directly. Therefore, we rely on detecting the consequences of haemolysis to determine the cause. What are these?
Increased red cell production and detection of breakdown products
What are the bone marrow’s two main responses to haemolysis?
Erythroid hyperplasia and reticulocytosis
Due to the presence of reticulocytes, when someone is haemolysing what will be seen on a blood film?
Large, polychromatic red cells (reticulocytes)
Is the presence of reticulocytes diagnostic of haemolysis?
No, because it can also be seen as a response to bleeding or iron therapy
How is erythroid hyperplasia actually visualised? Is this done often?
Bone marrow biopsy - no, only when you think the person is haemolysing because of a disorder that would show up on a biopsy
Where are red cells broken down in extravascular haemolysis?
They are taken up by the reticuloendothelial system, predominantly the liver and spleen
Where are red cells broken down in intravascular haemolysis?
Within the circulation
What effect does extravascular haemolysis have on the site of red cell destruction? Give examples?
It causes hyperplasia at the site of destruction - usually splenomegaly +/- hepatomegaly
In extravascular haemolysis, the protoporphyrin that forms the haem group gets broken down, leading to the release of what?
Unconjugated bilirubin in the blood / urobilinogen in the urine
In extravascular haemolysis, the release of unconjugated bilirubin into the blood leads to what clinical symptoms/signs?
Jaundice and gallstones
Describe the abnormality with the breakdown products in extravascular haemolysis?
They are normal breakdown products, just seen in excess
In intravascular red cell destruction, there is release of what into the circulation?
Free Hb (haemoglobinaemia) and Hb bound to albumin (methaemalbuminaemia)
In intravascular red cell destruction, there is release of what into the urine?
Hb (haemoglobinuria) and haemosiderin (haemosiderinuria)
How does the presence of Hb in the urine look?
Looks pink initially, but turns black when left to stand
What are some causes of intravascular red cell destruction?
ABO incompatibility, G6PD deficiency, severe falciparum malaria (Blackwater fever)
Describe the abnormality with the breakdown products which is seen in intravascular haemolysis?
Abnomal breakdown products are produced - these can be life threatening
Haemolysis can be classified by the site of red cell defect. Give some examples?
Abnormal cell membrane, Hb or red cell metabolism
What are the two main categories of acquired premature normal red cell destruction?
Immune or mechanical
What are the two main categories of immune premature red cell destruction?
Autoimmune or alloimmune haemolysis
Autoimmune haemolysis can be caused by what two antibodies?
Warm (IgG) or cold (IgM)
How is autoimmune haemolysis diagnosed?
Direct Coombe’s test - will show agglutination if positive for antibody
What is an example of alloimmune haemolysis which is caused by an immune response resulting in the production of antibodies?
Haemolytic transfusion reaction
What is an example of alloimmune haemolysis which is caused by passive transfer of antibodies?
Haemolytic disease of the newborn
What are some examples of mechanical causes of acquired premature destruction of red blood cells?
DIC, HUS, thrombotic thrombocytopenic purpura, leaking heart valve, infections e.g. malaria
Mechanical valve related microangiopathic haemolytic anaemia (MAHA) will show what on a blood film?
Red cell fragmentation
What is seen on a blood film of a patient with severe burns?
Microspherocytes and sheared red cells
What are some examples of acquired red cell membrane defects which can lead to haemolysis?
Liver disease (Zieve’s syndrome), vitamin E deficiency, paroxysmal noctural haemoglobinuria
Zieve’s syndrome is an example of an acquired red cell membrane defect. It involves a triad of what?
Haemolysis, alcoholic liver disease and hyperlipidaemia
Give two examples of causes of haemolysis due to congenital abnormalities of the red cell membrane?
Hereditary spherocytosis and G6PD deficiency
What is an example of haemolysis caused by congenital abnormal haemoglobin?
Sickle cell disease
What is a test you could do that is highly sensitive for haemolysis - i.e. if this is not raised then they are unlikely to be haemolysing?
Serum haptoglobins
What seen on a blood film is suggestive of mechanical damage to the red cell membrane?
Spherocytes
Red cell fragments on a blood film are suggestive of what?
Mechanical damage from an artifical heart valve
What is seen on a blood film which is suggestive of oxidative damage?
Heinz bodies
