Haemolysis

Question 1

What is haemolysis?

Answer 1

Premature red cell death

Question 2

Why are red cells to susceptible to damage?

Answer 2

Biconcave shape
Limited metabolic reserve and rely exclusively on glucose metabolism for energy (no mitochondria)
Can’t generate new proteins once in circulation (no nucleus)

Question 3

What is compensated haemolysis?

Answer 3

Increased red cell destruction compensated by increased red cell production = Hb maintained

Question 4

What is decompensated haemolysis?

Answer 4

Haemolytic anaemia = increased rate of red cell destruction exceeding bone marrow capacity for red cell production (Hb falls)

Question 5

What are the consequences of haemolysis?

Answer 5

Erythroid hyperplasia and excess red cell breakdown products

Question 6

What occurs in erythroid hyperplasia?

Answer 6

Increased bone marrow red cell production

Question 7

How is red cell survival assessed?

Answer 7

Can’t be measured routinely = rely on detecting consequences of haemolysis and investigate cause

Question 8

What are the bone marrow responses to haemolysis?

Answer 8

Reticulocytosis and erythroid hyperplasia

Question 9

Are reticulocytes nucleated?

Answer 9

No = still contain ribosomal RNA so appears polychromatic on blood film

Question 10

What is used to stain reticulocytes?

Answer 10

New methylene blue

Question 11

What occurs in automated reticulocyte counting?

Answer 11

Ribosomal RNA is labelled with a fluorochrome and fluorescent cells are counted

Question 12

How is haemolysis classed?

Answer 12

Extravascular = taken up by reticuloendothelial system (mainly spleen and liver)
Intravascular = red cells destroyed

Question 13

What are the features of extravascular haemolysis?

Answer 13

More common with normal products being in excess
Hyperplasia at site of destruction
Release of protoporphyrin

Question 14

What organs may become enlarged due to extravascular haemolysis?

Answer 14

Spleen and/or liver

Question 15

What does the release of protoporphyrin due to extravascular haemolysis cause?

Answer 15

Unconjugated bilirubinaemia and urobilinogenuria

Question 16

What occurs in intravascular haemolysis?

Answer 16

Red cell destroyed in circulation spilling their contents = abnormal products, may be life threatening

Question 17

What abnormalities may occur in intravascular haemolysis?

Answer 17

Haemoglobinaemia, methaemalbuminaemia, haemoglobinuria, haemosiderinuria

Question 18

How does haemoglobinuria present?

Answer 18

Causes pink urine that turns black on standing

Question 19

What are the causes of intravascular haemolysis?

Answer 19

ABO incompatible blood transfusion
G6PD deficiency and severe falciparum malaria
Rarely PNH or PCH

Question 20

What investigations can help confirm haemolytic state?

Answer 20

FBC and blood film, reticulocyte count, serum unconjugated bilirubin and heptoglobins, urinary urobilinogen

Question 21

How can the cause of haemolysis be identified?

Answer 21

History and examination = genetic or acquired

Blood film and Direct Coombs’

Question 22

What are the diagnostic blood film features of some cause if haemolysis?

Answer 22

Membrane damage = spherocytes
Oxidative damage = Heinz bodies
Mechanical damage = red cell fragments
HbS = sickle cells

Question 23

How is haemolysis classed?

Answer 23

Using site of red cell defect

Question 24

What are the different classes of haemolysis by site of red cell defect?

Answer 24

Premature destruction of normal red cells
Abnormal cell membrane
Abnormal red cell metabolism
Abnormal haemoglobin

Question 25

What are the acquired immune causes of haemolysis?

Answer 25

Autoimmune haemolysis and alloimmune haemolysis

Question 26

What are the types of autoimmune haemolysis?

Answer 26

Warm (IgG) and cold (IgM)

Question 27

What are the causes of warm autoimmune haemolysis?

Answer 27

Idiopathic (most common), autoimmune disorders, lymphoproliferative disorders, drugs, infection

Question 28

What are the causes of cold autoimmune haemolysis?

Answer 28

Idiopathic, infections, lymphoproliferative disorders

Question 29

How is autoimmune haemolysis diagnosed?

Answer 29

Direct Coombs' test = identifies antibody ad complement bound to own red cells

Question 30

How can alloimmune haemolysis arise?

Answer 30

Due to immune response or due to passive transfer of antibody

Question 31

What causes an immune response leading to alloimmune haemolysis?

Answer 31

Haemolytic transfusion reaction = immediate (IgM) mostly intravascular, delayed (IgG) mostly extravascular

Question 32

What is a trigger of passive antibody transfer causing alloimmune haemolysis?

Answer 32

Haemolytic disease of the newborn

Question 33

What are some acquired mechanical causes of haemolysis?

Answer 33

Mechanical red cell destruction Mechanical valve related microangiopathic haemolytic anaemia Burns releated haemolysis

Question 34

What are some causes of mechanical red cell destruction?

Answer 34

Disseminated intravascular coagulation, haemolytic uraemic syndrome, TTP, leaking heart valve, infections

Question 35

What occurs in mechanical valve related microangiopathic haemolytic anaemia?

Answer 35

Red cell fragmentation as a result of extrinsic damage

Question 36

What occurs in burns related haemolysis?

Answer 36

Red cells are sheared as they pass through damaged capillaries = microspherocytes present

Question 37

Are acquired cell membrane defects common?

Answer 37

No = all very rare

Question 38

What are some examples of acquired cell membrane defects?

Answer 38

Vitamin E deficiency, paroxysmal nocturnal haemoglobinuria, Zieve's syndrome

Question 39

What occurs in Zieve's syndrome?

Answer 39

Haemolysis with alcoholic liver disease and hyperlipidaemia = causes anaemia with polychromatic and irregularly contracted cells

Question 40

What are some examples of genetic cell membrane defects?

Answer 40

Reduced membrane deformability, increased transit time through spleen, oxidant environment in spleen causes extravascular haemolysis, hereditary spherocytosis

Question 41

What are some genetic causes of abnormal red cell metabolism?

Answer 41

G6PD deficiency = failure to cope with oxidant stress | Failure to generate ATP = metabolic processes fail

Question 42

What type of therapies can cause oxidative damage leading to haemolysis?

Answer 42

Dapsone and salasopyrin therapy

Question 43

What occurs in sickle cell disease?

Answer 43

Affects physical properties of Hb due to abnormal polymerisation resulting in shortened red cell survival

Question 44

What causes sickle cell disease?

Answer 44

Point mutations in beta globin chain