Haemolysis

Question 1

What is haemolysis?

Answer 1

Premature destruction of circulating red cells

Question 2

Why are red cells particularly susceptible to damage?

Answer 2

They have a biconcave shape

They have no mitochondria

They have no nucleus so cannot generate new proteins if they become damaged

Question 3

What is compensated haemolysis?

Answer 3

Increased red cell destruction matched by increased red cell production

Question 4

What is haemolytic anaemia?

Answer 4

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

Question 5

Give examples of consequences of haemolysis?

Answer 5

Erythroid hyperplasia (key point)

Reticulocytosis

Excess red cell breakdown products

Question 6

What is the main bone marrow response to haemolysis?

Answer 6

Erythroid hyperplasia

Question 7

What is typically seen on a blood film from a patient with haemolysis?

Answer 7

Polychromasia

Question 8

What are reticulocytes?

Answer 8

NON NUCLEATED cells that are the immediate precursor of a mature red cell

Question 9

What two things are needed to diagnose haemolysis?

Answer 9

Evidence of increased red cell production

AND

Evidence of increased red cell breakdown products

Question 10

What typically breaks down red cells?

Answer 10

Splenic macrophages

Question 11

What two symptoms are common in extravascular haemolysis patients?

Answer 11

Jaundice and dark urine

Question 12

What can be seen in intravascular haemolysis patients?

Answer 12

Haemoglobinaemia
(free Hb in circulation)

Haemoglobinuria
(free Hb ‘clogs’ kidneys and emerge in urine, urine is pink and turns black upon standing)

Methaemalbuminaemia
(free Hb binds to albumin)

Question 13

Which type of haemolysis is most common?

Answer 13

Extravascular haemolysis

Question 14

Which type of haemolysis is potentially life-threatening?

Answer 14

Intravascular haemolysis

Question 15

What can cause intravascular haemolysis?

Answer 15

ABO incompatible blood transfusion

Mechanical RBC trauma

Severe G6PD deficiency

Question 16

What test is used to confirm cause of haemolysis?

Answer 16

FBC + blood film

Question 17

What investigations can identify the cause of haemolysis?

Answer 17

History + examination

Blood film - membrane damage

Specialist investigations (Direct Coomb’s test and others)

Question 18

What will the reticulocyte count, serum unconjugated bilirubin, urinary urobilinogen and lactate dehydrogenase levels show on a FBC in haemolysis?

Answer 18

They will be raised

Question 19

What will serum haptoglobin levels show on a FBC in haemolysis?

Answer 19

It will be decreased

Question 20

What is autoimmune haemolysis?

Answer 20

A condition in which an autoantibody binds to self proteins on red cells

Question 21

What can Warm (IgG) autoantibody haemolysis be caused by?

Answer 21

Idiopathic, autoimmune disorders, lymphoproliferative disorders, drugs, infections

Question 22

What can Cold (IgM) autoantibody haemolysis be secondary to?

Answer 22

Infections, lymphoproliferative disorders - lymphoma, leukaemia

Question 23

What is alloimmune haemolysis caused by?

Answer 23

Immune response - immediate or delayed
(mismatched blood OR immune response to another antigen RhD)

Passive transfer of antibody (haemolytic disease of newborn)

Question 24

Give examples of mechanical destruction of red cells?

Answer 24

March haemoglobinuria

Damaged heart valve

Damaged microcirculation (severe burns, fibrin strand deposition)

Question 25

What are the less common abnormal situations that can cause haemolysis?

Answer 25

Toxins e.g. chlostridia Snake venoms Rupture of infected red cells by malaria parasites

Question 26

What causes microspherocytes on a blood film?

Answer 26

Severe burns - the cells are sheared as they pass through damages capillaries

Question 27

What is a spherocyte?

Answer 27

Red cells with molecular defects in one or more proteins in the cytoskeleton of red cells

Question 28

Give some causes of abnormalities of the cell membrane causing haemolysis?

Answer 28

Hereditary spherocytosis (typically autosomal dominant) Warm (IgG) haemolytic anaemia Delayed transfusion reaction Haemolytic disease of the newborn

Question 29

Give properties of G6PD deficiency?

Answer 29

X-linked condition Hundreds of different mutations Varying levels of functional deficiency

Question 30

What happens in G6PD deficiency?

Answer 30

Decreased G6PD results in decreased generation of NADPH - GSH levels no longer maintained, meaning less prevention of oxidative damage Is a failure to cope with oxidative stress

Question 31

What is a Heinz body?

Answer 31

A condensed precipitate of oxidised globulins

Question 32

What can commonly occur due to abnormal haemoglobin structure?

Answer 32

Sickle cell disease (HbSS)

Question 33

What causes abnormal haemoglobin structure in sickle cell disease?

Answer 33

A point mutation in beta chain

Question 34

What are some causes of chronic haemolytic anaemia?

Answer 34

Hereditary spherocytosis Thalassaemia Sickle cell anaemia G6PD deficiency

Question 35

What are schistocytes?

Answer 35

Fragments of red blood cells

Question 36

What is hereditary spherocytosis?

Answer 36

An inherited autosomal dominant haemolytic anaemia that causes fragile sphere-shaped RBCs

Question 37

How is hereditary spherocytosis managed?

Answer 37

Folic acid - folate supplementation Blood transfusions when required Splenectomy

Question 38

How is autoimmune haemolytic anaemia managed?

Answer 38

Blood transfusions Prednisolone Rituximab Splenectomy

Question 39

In what two scenarios can alloimmune haemolytic anaemia occur?

Answer 39

Transfusion reactions Haemolytic disease of the newborn

Question 40

What is microangiopathic haemolytic anaemia?

Answer 40

The destruction of red cells as they travel through circulation often caused by abnormal activation of the clotting system

Question 41

What is thrombotic microangiopathy?

Answer 41

Small thrombi partially obstructing the small blood vessels, commonly those in peripheries

Question 42

What can microangiopathic haemolytic anaemia be secondary to?

Answer 42

Haemolytic uraemic syndrome (HUS) Disseminated intravascular coagulation (DIC) Thrombotic thrombocytopenic purpura (TTP) Systemic lupus erythematosus (SLE)

Question 43

What is the key finding on a blood film in patients with microangiopathic haemolytic anaemia?

Answer 43

Schistocytes