Week 1- Haemolysis

Question 1

What is heamolysis?

Answer 1

Premature red cell destruction (shortened red cell lifespan)

Question 2

Why are red cells particularly susceptible to damage?

Answer 2

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)

Question 3

NOTE

Answer 3

Not everyone who has haemolysis is anaemic.

Question 4

What is compensated haemolysis?

Answer 4

Increased red cell destruction compensated by increased red cell production. Therefore Hb is maintained.

Question 5

What is haemolytic anaemia?

Answer 5

Increased rate of red cell destruction exceeding bone marrow capacity for red cell production. Therefore Hb falls.

Question 6

What are some consequences of haemolysis?

Answer 6

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

Question 7

NOTE

Answer 7

It is really difficult to measure red cell survival rate, so you have to measure it in round about ways.

Question 8

What is the bone marrows response to haemolysis?

Answer 8

Reticulocytosis

Erythroid hyperplasia

Question 9

What will a blood film in a patient with haemolysis show?

Answer 9

Polychromatic (due to high number of reticulocytes).

Question 10

How can haemolysis be classified?

Answer 10

Classified in regards to site of red cell destruction- extravascular or intravascular.

Question 11

How can haemolysis be classified?

Answer 11

Classified in regards to site of red cell destruction- extravascular or intravascular.
Can also be classified by site of red cell defect.

Question 12

Where does intravascular haemolysis occur?

Answer 12

Red cells are destroyed within the circulation.

Question 13

Which type of haemolysis is more common?

Answer 13

Extravascular

Question 14

What signs point you towards thinking its an extravascular cause rather than an intravascular cause?

Answer 14

Splenomegaly +/- hepatomegaly- organs get bigger because they are doing more work.
Release of protoporthyrin- broken down to make bilirubin causing jaundice, gallstones, urobilinogenuria

Question 15

What signs point you towards thinking its an extravascular cause rather than an intravascular cause?

Answer 15

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.

Question 16

What signs point you towards thinking it is an intravascular cause rather than an extravascular cause?

Answer 16

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.

Question 17

What scenarios might you get an intravascular haemolysis occurring?

Answer 17

ABO incompatible blood transfusion
G6PD deficiency
Severe falciparum malaria (blackwater fever- urine goes black as Hb is released into the urine)

Question 18

Which blood investigations would you do into haemolysis?

Answer 18

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.

Question 19

What may a blood film show which indicate you towards a a cause of haemolysis?

Answer 19

Spherocytes- sickle cell anaemia or hereditary spherocytosis
Mechanical damage- red cell fragments
Oxidative damage- Heinz bodys
Others e.g. sickle cells

Question 20

Another way to classify is by site of red cell defect, outline where can the red cell defects could be?

Answer 20

Can be 
1-premature destruction of normal red cells (autoimmune or mechanical)
2-abnormal cell membrane
3-abnormal red cell metabolism
4-abnormal haemoglobin

Question 21

What is meant by autoimmune destruction?

Answer 21

Patients own antibodies are destroying the red cells.

Question 22

What is meant by alloimmune destruction?

Answer 22

foreign antibodies are destroying the patients red cells.

Question 23

How can autoimmune haemolysis be classified?

Answer 23

Can either be IgG (warm) or IgM (cold) causes.

Question 24

Which type of autoimmune haemolysis is most common?

Answer 24

IgG is most common.

Question 25

Name some causes of IgG mediated autoimmune haemolysis?

Answer 25

Most often it is idiopathic
Can sometimes be associated with autoimmune disorders e.g. SLE
Lymphoproliferative disorders 
Drugs e.g. penicillin
Infection

Question 26

Name some causes of IgM mediated autoimmune haemoylsis?

Answer 26

Idiopathic
Infections (EBV, mycoplasma)
Lymphoproliferative disorders

Question 27

Which test would you use to diagnose an IgG cause of haemolysis? Describe this test?

Answer 27

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.

Question 28

What can cause alloimmune haemolysis?

Answer 28

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.

Question 29

What mechanical causes of red cell destruction can occur to cause haemolysis?

Answer 29

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

Question 30

What can cause abnormal cell membrane defects in RBC’s causing haemolysis?

Answer 30

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

Question 31

What can cause abnormal red cell metabolism?

Answer 31

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.

Question 32

What congenital causes of abnormal haemoglobin can cause red cell haemolysis?

Answer 32

Sickle cell disease