Allo-Antibodies Flashcards

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1
Q

What are allo=antibodies?

A

Antibodies that are found that are against antigen that are not on your own red blood cells.

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2
Q

Which type of immune response is IgG mostly concerned with?

A

Secondary

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3
Q

Which type of immune response are IgM antibodies most concerned with?

A

Primary

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4
Q

Do IgG antibodies have placental transfer?

A

Yes

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5
Q

Do IgM antibodies have placental transfer?

A

No

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6
Q

Do IgG and IgM antibodies activate complement?

A

Yes

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7
Q

What is the optimal reaction temperature for IgG antibodies?

A

37 degrees celsius

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8
Q

What is the ideal temperature for the reaction of IgM antibodies.

A

4-20 degrees celsius

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9
Q

Do Allo-antibodies cause haemolytic or delayed transfusion reactions?

A

No they have not been discovered to be clinically significant.

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10
Q

Do IgM antibodies cause haemolytic diseases of the foetus and newborn.

A

No because they cannot cross the placental barrier.

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11
Q

How do Allo-antibodies cause acute haemolytic reaction?

A

They activate complement and cause macrophages to recognise red cell bound antibodies.

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12
Q

Outline what happens during Intravascular Haemolysis.

A

An antibody binds to a red cell membrane and activates complement.

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13
Q

In intravascular haemolysis, what is complement used for?

A

To destroy any invading cells.

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14
Q

What happens after the complement system has been activated during intravascular haemolysis?

A

Channels are formed through the cell membranes and cause haemolysis.

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15
Q

In intravascular haemolysis, where are the red cells that are lysed?

A

Inside the blood vessels.

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16
Q

In what type of patients is intravascular haemolysis common?

A

People who have had an ABO incompatible transfusion.

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17
Q

What are the clinical phases of Acute Haemolytic Reaction?

A

Haemolytic shock
Post shock evidence of haemolysis
Oliguric
Diuretic

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18
Q

Outline what occurs to cause haemolytic shock

A

Lysis of red cells causes circulation of free haemoglobin and remnants of red cell membrane. This combined with the complement cascade results in activation of the coagulation cascade.
This leads to DIC

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19
Q

What is disseminated intravascular coagulation?

A

Many small thromboses are deposited in vessels in most organs. As the clotting factors begin to be consumed, there is an increased risk of simultaneous haemorrhage, especially whilst undergoing surgery.

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20
Q

What does DIC stand for?

A

Disseminated intravascular coagulation

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21
Q

What clinical symptoms does circulatory shock due to lack of red cells lead to?

A
Hypotension
Tachycardia
Chills
Rapid and shallow breathing
Chest and lumbar pain
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22
Q

Why does circulatory shock due to lack of red cels cause hypotension?

A

Cytokine release leads to vasodilation which results in hypotension.

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23
Q

Why does circulatory shock due to lack of red cels cause Tachycardia?

A

Heart beats faster to maintain blood pressure

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24
Q

Why does circulatory shock due to lack of red cels cause chills?

A

Vasoconstriction to maintain BP

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25
Q

Why does circulatory shock due to lack of red cels cause chest pain?

A

Cytokine release constricts gut and smooth lung muscle

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26
Q

What mental symptoms is caused by circulatory shock due to lack of red cells and why?

A

A sense of impending doom. Release of inflammatory cytokines causes this.

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27
Q

What are the evidence factors that suggest acute haemolytic reaction?

A
Haemoglobinnuria
Drop in Hb
Raise bilirubin
Jaundice
Blood film shows agglutination, spherocytes and red cell fragments.
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28
Q

What is Oliguric (phase 3 of the acute haemolytic reaction)?

A

Free haemoglobin in the blood causes toxic acute tubular necrosis and leads to cute renal failure.

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29
Q

What are some of the consequences of acute haemolytic reaction?

A

Renal tubes remain scarred.
Spontaneous diuresis.
Electrolyte imbalance
Slow recovery or permanent renal damage

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30
Q

What is diuresis?

A

Extra fluid loss via uric.

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31
Q

Outline what occurs during delayed haemolytic reaction.

A

Macrophages in the spleen monitor circulating red blood cells fro bound IgG antibodies and either remove the whole cell from the circulation or remove the part of the membrane with the bound antibody.

32
Q

What would form if the membrane with a bound antibody is removed from a red blood cell?

A

A spherocyte

33
Q

What happens when red cells carrying IgG antibodies are removed from the circulation during delayed haemolytic reaction?

A

Bilirubin levels increase.

34
Q

What can bilirubin cause if levels become irregular?

A

Jaundice and yellowing of the skin and eyes.

35
Q

Is delayed haemolytic reaction intravascular or extravascular ?

A

Extravascular

36
Q

Is acute haemolytic reaction intravascular or extravascular?

A

Intravascular

37
Q

How quickly does delayed haemolytic reaction occur after transfusion?

A

24 hours after or more

38
Q

Why don’t IgG antibodies cause agglutination?

A

They are small and so cannot bridge a gap between two red cells. this is also due to the negative charges the red cells contain.

39
Q

Can IgM antibodies cause agglutination of red cells?

A

Yes

40
Q

Can IgG antibodies cause agglutination of red cells?

A

No

41
Q

Outline the process of an Indirect Anti-globulin test

A

Add patent plasma sample.
Incubate with red cells at 37 degrees celsius.
Centrifuge the sample.
Add anti-human globulin.

42
Q

What is the other nae for an Indirect Anti-globulin test?

A

Indirect Coombs Test

43
Q

In the Indirect Antiglobulin test, why are the cells inclubated?

A

Allows antibodies to bind to reagent red cells

44
Q

In the Indirect Antiglobulin test, why is the sample centrifuged?

A

Forces the red cells down the column which contains anti-human globulin.

45
Q

In the Indirect Antiglobulin test, why is anti-human globulin added?

A

It enables agglutination of red cells mediated by IgG antibodies.

46
Q

In an initial antibody screening test, how many different types of screening cell are used?

A

3

47
Q

What is a positive regulation in an Antibody screening?

A

Agglutination

48
Q

What is added during an antibody screening to form the agglutination and let us know which antigens cause a positive reaction?

A

Anti-human globulin

49
Q

What factor must be known about screening cells in an antibody screening?

A

Their phenotype

50
Q

In an identification panel, what is reacted?

A

Patient plasma with red cells

51
Q

How long are the reagents incubated for in an identification panel?

A

15 minutes

52
Q

What must occur in a screening panel for antibody specificity to be assigned?

A

The plasma must have been reactive with at least two examples of reagent red cells expressing the antigen and non-reactive with at least two examples of reagent red cells lacking the antigen.

53
Q

Once one antibody specificity has been identified by a screening panel, what must happen?

A

The presence or absence of additional clinically significant antibodies is established.

54
Q

What is the dosage effect?

A

The effect of seeing stronger reactions with homozygous antigen expression compared to heterozygous expression.

55
Q

What are frequent causes of false positive reactions in antibody screening?

A

Autoantibodies
Drug treatment
Mixed up panel sheets

56
Q

What is pan agglutination?

A

When people agglutinate with all antibody types in a screening panel.

57
Q

What method is often used to confirm the results of an identification panel ?

A

Phenotyping

58
Q

In terms of confirming the results of an identification panel using phenotyping, how should the results compare?

A

A patient should be antigen negative for the corresponding antibody.

59
Q

Can phenotyping detect allo-antibodies?

A

Yes

60
Q

Can phenotyping detect autoantibodies?

A

No

61
Q

Define phenotype.

A

The expression of antigens determined by a patients genotype.

62
Q

What blood matches are transfusion patients given where possible?

A

Rh and Kell matched

63
Q

When is genotyping used in terms of transfusion?

A

When a patient has been recently transfused so phenotyping is unreliable.

When strong autoantibodies or drug therapy are interfering with phenotyping results.

For haemoglobinopathy patients who are transfusion dependent.

64
Q

What process do NHSBT use to carry out genotyping?

A

PCR

65
Q

Why is genotyping not used for ABO grouping?

A

If you are a group O Bombay, you can be A, B or AB, but your blood can group can appear as type O. Therefore they could easily be transfused with incompatible blood if genotyping was to be used.

66
Q

What does frequency of red cell allo-antibodies depend on?

A

Frequency of antigens in different ethnic groups.

Frequency of antigens in donor population.

67
Q

What are ‘responders’?

A

Alloimunized patients are a genetically distinct group with an increased susceptibility to RBC sensitisation. In transfusion these patients are known as responders.

68
Q

As the number of antibodies goes up, how does the proportion of donor available compatible blood alter?

A

Decreases

69
Q

My phenotype is K+(a+b+) Jk(a-b+). What red cell allo-antibodies could I form?

A

Anti-Jka

70
Q

In what ways do antibody’s destroy red cells?

A
  • Complement binds and leads to intravascular haemolysis.
  • Bound antibody is recognised by the spleen and removed creating Spherocytes which are subsequently destroyed.
  • Bound antibody is recognised by the spleen/ liver and the whole red cell is removed, leading to extravascular haemolysis.
71
Q

Spherocytes are a sign of acute transfusion reaction, true or false?

A

False

72
Q

The liver is at risk of permanent damage following a transfusion reaction, true or false?

A

False

73
Q

Which blood group system is most commonly associated with delayed transfusion reactions?

A

Kidd

74
Q

An enzyme treated panel is useful when there are multiple antibody specificities, true or false?

A

True

75
Q

As the number of all-antibodies increases, how does the availability of compatible blood change?

A

Decreases

76
Q

Why do Kill (Jk and Job) antibodies frequently give a negative antibody screen?

A

They disappear over time.

77
Q

What happens when a patient is transfused with blood which is positive for Jka or Job and they have previously had these antibodies?

A

Antibody production will be stimulated and the transfused cells will be coated. These will then be recognised by the spleen and liver as abnormal and destroyed.