Haemolysis Flashcards
What is haemolysis?
Premature red cell destruction i.e. shortened red cell survival in the circulation
Why are red cells particularly 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)
- Cannot generate new proteins once in circulation as they do not have a nucleus
What is compensated haemolysis?
Increased destruction of red cells coupled with an increased production of red cells i.e. Hb is maintained
What is haemolytic anaemia (decompensated haemolysis)?
Increase rate of red cell destruction exceeding bone marrow capacity for red cell production i.e. Hb falls
What are the consequences of haemolysis?
Erythroid hyperplasia (increased bone marrow red cell production) Excess red cell breakdown products e.g. bilirubin
What is the bone marrow response to haemolysis?
Reticulocytosis
Erythroid hyperplasia
What is important to remember about reticulocytes?
They do not have a nucleus! (do have RNA remnants etc but no nucleus)
What is the appearance of reticulocytosis on blood film
Polychromasia ( due to rRNA)
Large cells
What are the two broad classifications of haemolysis?
Extravascular= taken up by reticuloendothelial system eg spleen and liver Intravascular= red cells destroyed within the circulation
Different classification- therefore different breakdown products detected
Knowing whether it is intra/extra helps determine cause of haemolysis
Which is more common; intra or extravascular red cell destruction?
Extravascular
What are the feautres of an extravascular red cell destruction
Hypeplasia of site of destruction - splenomegaly, hepatomegaly
Release of protoporphyrin
-unconjugated biliribinaemia resulting in jaundice or gallstone
-urobilinogenuria
Normal products are in excess.
What are the features of intravascular red cell destruction?
Red cells are destroyed in the circulation therefore spilling their contents.
- Haemoglobinaiemia (free Hb in circulation)
- Methaemalbuminaemia
- Haemoglobinuria (pink urine, turns black on standing)
- Haemosiderinuria
Abnormal products
This type of haemolysis can be life threatening!
What are the causes of intravascular haemolysis
ABO incompatible blood transfusion
G6PD deficiency
Severe falciparum malaria (blackwater fever)
PNH, PCH (paroxysmal nocturnal haemoglobinuria, paroxysmal cold haemoglobinurea)- v. rare
What investigations are done to confirm a haemolytic state?
FBC and blood film Reticulocyte count Serun unconjugated bilirubin Serum haptoglobins Urinary urobilinogen
What tests are done to try determine the cause of haemolysis
Membrane damage - spherocytes
Mechanical damage- red cell fragments
Oxidative damage - Heinz bodies
Others eg HbS - sickle cell
Direct coombs test
what are the possible sites of a red cell defect
1/ premature destruction of normal cells
2. abnormal cell membrane
3. abdnormal red cell metabolism
4 abnormal haemoglobin
What causes premature destruction of red cells
Autoimmune or alloimmune haemolysis
What are the forms of autoimmune haemolysis?
Warm or cold auto-antibody
Warm(IgG) - Idiopathic (commonest)
- Autoimmune (SLE)
- Lymphoprofiferative disorders (CLL)
- Drugs (penicillins etc)
- Infections
Cold (IgM) -Idiopathic
- Infections (EBV, mycoplasma)
- Lymphoproliferative disorders
what is direct coombs test?
Used to identify antibody and compliment bound to own red cells.
if agglutination occurs = positive
What are the causes of alloimmune haemolyis?
Immune response (antibody produced) - haemolytic transfusion reaction either delayed (IgG) or immediate (IgM)
Passive transfer of antibody - haemolytic disease of the newborn
name some acquired causes of haemolysis
Mechanical red cell destruction eg
- disseminated intravascular coagulation
- Haemolytic uraemic syndrome (E. colli 0157)
- Thrombotic thrombocytopenic purpura
- Leaking hear valve
- Infections eg malaria
WHy does a valvular problem result in haemolytic anaemia
Microangiopathic haemolytic anaemia occurs because the red cells fragment as a result of mechanical damage due to a diseased valve.
How does burns cause haemolysis
red cells are sheared as they pass through damages capillaries so only seen in sever burns
Microspherocytes
What acquire membrane defects can cause haemolyis
Liver disease (sieve's syndrome) Vitamin E deficiency Paroxysmal nocturnal haemoglobinuria
