Haemolysis

Question 1

What is haemolysis?

Answer 1

Premature red cell destruction

Question 2

What is the difference between compensated and decompensated haemolysis?

Answer 2

Compensated = Hb maintained by increased red cell production

Decompensated = rate of red cell destruction exceeding bone marrow capacity for production (haemolytic anaemia)

Question 3

What are the consequences of haemolysis used to identify in on investigation?

Answer 3

Erythroid hyperplasia (increased bone marrow production of red cells) --> reticulocytosis
Excess red cell breakdown products

Question 4

What does reticulocytosis look like on a blood film?

Answer 4

Polychromasia (different colours) –> due to ribosomal RNA in reticulocytes (NOT nucleated)

Question 5

How is haemolysis classified and how can you tell the difference?

Answer 5

Intravascular vs extravascular

–> different breakdown products

Question 6

Where are the red cells destroyed in extravascular haemolysis?

Answer 6

Liver and spleen –> hyperplasia (hepatosplenomegaly)

Question 7

Which breakdown products are seen in extravascular haemolysis?

Answer 7

Normal products in excess:

• unconjugated bilirubinaemia (jaundice, gall stones)
• urobilinogenuria

Question 8

Which breakdown products are seen in intravascular haemolysis?

Answer 8

Haemoglobinaemia (free Hb in circulation)
Methaemalbuminaemia
Haemoglobinuria (pink urine, turns black on standing)
Haemosiderinuria

–> abnormal products, may be life threatening

Question 9

What are the causes of intravascular haemolysis?

Answer 9

ABO incompatible blood transfusion
G6PD deficiency
Severe falciparum malaria (Blackwater fever)
PNH or PCH (very rare)

Question 10

How is autoimmune haemolysis classified?

Answer 10

Warm or cold autoantibody

• warm = IgG
• cold = IgM

Question 11

What are the causes of warm autoimmune haemolysis?

Answer 11

Idiopathic (most common)
SLE
CLL
Drugs e.g. penicillins
Infection

Question 12

What are the causes of cold autoimmune haemolysis and how is it triggered?

Answer 12

Idiopathic
Infection (EBV, mycoplasma)
Lymphoproliferative disorders

Triggered by: cold weather, cold drinks, unwarmed IV fluids etc

Question 13

How is autoimmune haemolysis diagnosed?

Answer 13

Direct Coombs’ test

Question 14

How does the Direct Coombs’ test work?

Answer 14

Patient RBCs + mouse anti-human IgG –> agglutination

–> identifies antibody bound to OWN red cells

Question 15

Give two examples of allogenic haemoylsis?

Answer 15

Haemolytic transfusion reaction (immune response - antibodies produced)
Haemolytic disease of the newborn (passive transfer of antibody)

Question 16

Give some examples of haemolysis caused by abnormal cell membranes

Answer 16

Genetic:
- Hereditary spherocytosis

Acquired:

• Zieve’s syndrome
• Vitamin E deficiency
• Paroxysmal nocturnal haemoglobinuria (PNH)
• (all very rare)

Question 17

What is Zeive’s syndrome?

Answer 17

Haemolysis, alcohol liver disease + hyperlipidaemia

Question 18

What is Paroxysmal nocturnal haemoglobinuria (PNH)?

Answer 18

Triad of:

• haemolytic anaemia
• pancytopenia
• large vein thrombosis

Question 19

What is the inheritance pattern of hereditary spherocytosis?

Answer 19

Autosomal dominant

Question 20

What is the pathophysiology of hereditary spherocytosis?

Answer 20

Sphere shaped red cells:

• reduced membrane deformability
• increased transit time in spleen
• oxidative environment in spleen causes extravascular red cell destruction

Question 21

Which genetic conditions cause haemolysis due to abnormal red cell metabolism? How are they inherited?

Answer 21

G6PD deficiency –> X linked

Pyruvate kinase deficiency –> autosomal recessive

Question 22

What causes the haemolysis in G6PD deficiency?

Answer 22

Failure to cope with oxidative stress
Haemolysis triggered by:
- infection
- drugs (primaquine, chloroquine, sulphonamides)
- fava beans --> FAVISM

Question 23

Which conditions cause haemolysis due to abnormal Hb?

Answer 23

Sickle cell disease

Thalassaemia

Question 24

What is Microangiopathic Haemolytic Anaemia (MAHA)?

Answer 24

Traumatic intravascular destruction of RBCs, often with endothelial injury, clotting activation + platelet aggregation

Question 25

Give some examples of MAHA?

Answer 25

Thrombotic thrombocytopenia purpura (TTP)
Haemolytic uraemic syndrome (HUS)
Disseminated intravascular coagulation (DIC)
HELLP syndrome
Autoimmune: vasculitis, SLE, scleroderma renal crisis
Mechanical heart valves
Malignant hypertension
Severe burns (red cells sheared as they pass through damaged capillaries)

Question 26

What are the clinical features of haemolysis?

Answer 26

Pallor, fatigue, SOB
Pre-hepatic jaundice
Splenomegaly
RUQ pain if there are pigment gallstones

Question 27

How is warm AI haemolysis treated?

Answer 27

Steroids first line
Other immunosuppressants e.g. rituximab, cyclophosphamide, azathioprine
Plasmapheresis
Splenectomy if refractory

Question 28

How is cold AI haemolysis treated?

Answer 28

Avoid cold, use warmed IV fluids/transfusion if needed

Usually mild so not requiring immunosuppression

Question 29

What is the treatment for hereditary spherocytosis?

Answer 29

Transfusions
Folic acid (required for RBC production)
Splenectomy

Question 30

What is the treatment for TTP?

Answer 30

Plasma exchange

- 90% mortality if untreated