Haemolysis

Question 1

Define haemolysis

Answer 1

Premature red cell destruction

Question 2

Why are red cells particularly susceptible to damage?

Answer 2

Biconcave shape
Limited metabolic reserve (no mitochondria)
Can’t generate new proteins (no nucleus)

Question 3

Define compensated haemolysis

Answer 3

Increased red cell destruction compensated by increased red cell production

Question 4

Define decompensated haemolysis

Answer 4

Increased rate of red cell destruction exceeding bone marrow capacity for red cell production

Question 5

What are the consequences of haemolysis?

Answer 5

Erythroid hyperplasia (increased bone marrow rbc production)
Excess red cell breakdown products

Question 6

What is the bone marrow response to haemolysis?

Answer 6

Reticulocytosis and erythroid hyperplasia

Question 7

What is extravascular haemolysis?

Answer 7

Red cells are taken up by the reticuloendothelial system (mainly spleen and liver)

Question 8

What is intravascular haemolysis?

Answer 8

Red cells destroyed within the circulation

Question 9

What is the difference between extravascular and intravascular haemolysis?

Answer 9

Location, mechanism and breakdown products.

Question 10

What is released during extravascular haemolysis and what is the result?

Answer 10

Protoporphyrin

Unconjugated bilirubinaemia, jaundice, gall stones, urobilinogenuria

Question 11

What is the result of intravascular haemolysis?

Answer 11

Haemoglobinaemia
Methaemalbuminaemia
Haemoglobinuria (pink urine, turns black on standing)
Haemosiderinuria

Question 12

What are the causes of intravascular haemolysis?

Answer 12

ABO incompatible blood transfusion
G6PD deficiency
Severe falciparum malaria
PNH/PCH

Question 13

What investigations are used to confirm a haemolytic state?

Answer 13

FBC (blood film)
Reticulocyte count
Serum unconjugated bilirubin
Serum haptoglobins
Urinary urobilinogen

Question 14

Investigations to identify the cause of a haemolytic state

Answer 14

History/examination: Genetic/acquired
Blood film: membrane damage (spherocytes)
Mechanical damage (rbc fragments)
Oxidative damage (heinz bodies)
Others (sickle cells)
Specialist investigations e.g. direct coombs test

Question 15

How is haemolysis classified in terms of site of red cell defect?

Answer 15

Premature destruction of normal rbcs (autoimmune or mechanical)
Abnormal cell membrane
Abnormal red cell metabolism
Abnormal haemoglobin

Question 16

Immune causes of haemolysis

Answer 16

Autoimmune, alloimmune

Question 17

Causes of warm (IgG) haemolysis?

Answer 17

Idiopathic
Autoimmune (SLE)
Lymphoproliferative disorders (CLL)
Drugs (penicillin)
Infection

Question 18

Causes of cold (IgM) haemolysis?

Answer 18

Idiopathic
Infection (EBV, mycoplasma)
Lymphoproliferative disorders

Question 19

Causes of alloimmune haemolysis

Answer 19

Haemolytic transfusion reaction

Haemolytic disease of the newborn

Question 20

Causes of mechanical red cell destruction.

Answer 20

DIC
Haemolytic uraemic syndrome
TTP
Leaking heart valve
Infection e.g. malaria

Question 21

Causes of red cell membrane defects?

Answer 21

Liver disease
Vitamin E deficiency
Paroxysmal nocturnal haemoglobinuria

Question 22

How are red cell membrane abnormalities caused?

Answer 22

Reduced membrane deformability
Increased transit time through spleen
Oxidant environment in spleen leads to extravascular red cell destruction
Hereditary spherocytosis

Question 23

What condition causes abnormal red cell metabolism?

Answer 23

G6PD deficiency (failure to cope with oxidant stress)

Question 24

What abnormalities does dapsone therapy lead to?

Answer 24

Keratocytes and abnormally contracted red cells

Question 25

Name a genetic cause of haemolysis

Answer 25

Sickle cell anaemia

Question 26

What causes sickle cell anaemia?

Answer 26

Point mutation in beta globin chain