Haemolysis Flashcards

1
Q

What is haemolysis?

A

Premature red cell death

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2
Q

Why are red cells to susceptible to damage?

A

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)

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3
Q

What is compensated haemolysis?

A

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

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4
Q

What is decompensated haemolysis?

A

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

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5
Q

What are the consequences of haemolysis?

A

Erythroid hyperplasia and excess red cell breakdown products

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6
Q

What occurs in erythroid hyperplasia?

A

Increased bone marrow red cell production

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7
Q

How is red cell survival assessed?

A

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

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8
Q

What are the bone marrow responses to haemolysis?

A

Reticulocytosis and erythroid hyperplasia

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9
Q

Are reticulocytes nucleated?

A

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

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10
Q

What is used to stain reticulocytes?

A

New methylene blue

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11
Q

What occurs in automated reticulocyte counting?

A

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

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12
Q

How is haemolysis classed?

A
Extravascular = taken up by reticuloendothelial system (mainly spleen and liver)
Intravascular = red cells destroyed
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13
Q

What are the features of extravascular haemolysis?

A

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

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14
Q

What organs may become enlarged due to extravascular haemolysis?

A

Spleen and/or liver

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15
Q

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

A

Unconjugated bilirubinaemia and urobilinogenuria

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16
Q

What occurs in intravascular haemolysis?

A

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

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17
Q

What abnormalities may occur in intravascular haemolysis?

A

Haemoglobinaemia, methaemalbuminaemia, haemoglobinuria, haemosiderinuria

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18
Q

How does haemoglobinuria present?

A

Causes pink urine that turns black on standing

19
Q

What are the causes of intravascular haemolysis?

A

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

20
Q

What investigations can help confirm haemolytic state?

A

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

21
Q

How can the cause of haemolysis be identified?

A

History and examination = genetic or acquired

Blood film and Direct Coombs’

22
Q

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

A

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

23
Q

How is haemolysis classed?

A

Using site of red cell defect

24
Q

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

A

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

25
Q

What are the acquired immune causes of haemolysis?

A

Autoimmune haemolysis and alloimmune haemolysis

26
Q

What are the types of autoimmune haemolysis?

A

Warm (IgG) and cold (IgM)

27
Q

What are the causes of warm autoimmune haemolysis?

A

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

28
Q

What are the causes of cold autoimmune haemolysis?

A

Idiopathic, infections, lymphoproliferative disorders

29
Q

How is autoimmune haemolysis diagnosed?

A

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

30
Q

How can alloimmune haemolysis arise?

A

Due to immune response or due to passive transfer of antibody

31
Q

What causes an immune response leading to alloimmune haemolysis?

A

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

32
Q

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

A

Haemolytic disease of the newborn

33
Q

What are some acquired mechanical causes of haemolysis?

A

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

34
Q

What are some causes of mechanical red cell destruction?

A

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

35
Q

What occurs in mechanical valve related microangiopathic haemolytic anaemia?

A

Red cell fragmentation as a result of extrinsic damage

36
Q

What occurs in burns related haemolysis?

A

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

37
Q

Are acquired cell membrane defects common?

A

No = all very rare

38
Q

What are some examples of acquired cell membrane defects?

A

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

39
Q

What occurs in Zieve’s syndrome?

A

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

40
Q

What are some examples of genetic cell membrane defects?

A

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

41
Q

What are some genetic causes of abnormal red cell metabolism?

A

G6PD deficiency = failure to cope with oxidant stress

Failure to generate ATP = metabolic processes fail

42
Q

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

A

Dapsone and salasopyrin therapy

43
Q

What occurs in sickle cell disease?

A

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

44
Q

What causes sickle cell disease?

A

Point mutations in beta globin chain