Allo-immunisation

Question 1

What is the basic process behind alloimmunisation?

Answer 1

Mother is exposed to an antigen. Mother produces an antibody. Antibody crosses placenta, leading to foetal sequelae

Question 2

What is the difference between maternal auto-antibodies and maternal allo/iso-antibodies?

Answer 2

Auto-antibody = antibody against antigen shared between mother and foetus (so mother will have autoimmune disease as well)
Allo/iso-antibody = antibody against antigen that mother doesn’t have (so only foetus will suffer consequences)

Question 3

Name 3 diseases associated with maternal auto-antibodies

Answer 3

Thyroid auto-immune disease
Connective tissue disease (SLE, Sjogren’s)
ITP

Question 4

Name 3 diseases associated with maternal allo-antibodies

Answer 4

Red cell allo-immunisation
Perinatal allo-immune thrombocytopaenia
Perinatal allo-immune neutropenia

Question 5

Name 3 red cell antigens that are potentially harmful (raise the risk of red cell allo-immunisation disease). Why are these antigens more dangerous than other red cell antigens (like ABO)?

Answer 5

Rhesus D, c, E
Kell, Kid, Duffy
MNS

Antibodies against these antigens are usually IgG = can cross placenta. Antibodies against ABO antigens are usually IgM = can’t cross placenta (so no foetal sequelae)

Question 6

What proportion of pregnancies will have red cell allo-immunisation? What is the most common RBC allo-antibody?

Answer 6

1% - most common is anti-D

Question 7

What proportion of people with RBC allo-immunisation will develop mild, moderate and severe symptoms? What symptoms are indicative of each level of severity?

Answer 7

Mild - 50% (mild haemolysis = mild jaundice).
Moderate - 25% (severe jaundice, mild anaemia).
Severe - 25% (severe anaemia, hydrops, FDIU).

Question 8

What is a consequence/sequelae of severe jaundice in a neonate?

Answer 8

In severe jaundice, bilirubin can cross the blood-brain barrier = brain damage (kernicterus)

Question 9

What is foetal hydrops?

Answer 9

Congestive cardiac failure in a foetus from severe anaemia, leading to generalised oedema (ascites, effusions) and potentially FDIU

Question 10

What is primary immunisation (in context of allo-immunisation)? Name 2 mechanisms through which can happen

Answer 10

Primary immunisation = mother’s initial exposure to antigen. Can occur through blood transfusion with insufficient matched blood, or feto-maternal haemorrhage (blood from foetus enters maternal circulation)

Question 11

Name 4 ways that feto-maternal haemorrhage can occur

Answer 11

Bleeding (abortion, ectopic, APH, miscarriage)
Trauma (CVS, amniocentesis, blunt trauma)
Delivery
Occult (spontaneous)

Question 12

How often does an occult feto-maternal haemorrhage occur? At what point in the pregnancy does this usually happen? How does this affect the timing of the preventative management for this?

Answer 12

Feto-Maternal haemorrhage occurs in 1% of pregnancies. Usually occurs after 28 weeks, therefore we give prophylactic anti-D at 28 and 34 weeks if woman is Rh-negative

Question 13

What do you do in relation to allo-immunisation for all women in the first antenatal visit?

Answer 13

Take blood type, and screen for existing anti red cell antibodies (1% of population)

Question 14

What proportion of women are Rh-negative?

Answer 14

15%

Question 15

If a woman is Rh-negative, what 2 things should you check in relation to allo-immunisation in the first antenatal visit?

Answer 15

Anti-D antibody titre - for Risk allocation (put into mild, moderate and severe risk categories based on titre levels)

Partner grouping (if mother is D-negative, see if father has a D antigen; if not, then no chance of foetus being D positive)

Question 16

If a woman is Rh-negative and her partner is heterozygous for D (D/d), what do you need to do to confirm whether she is at risk of developing anti-D antibodies? Name 2 ways you can do this

Answer 16

Take foetal DNA to see whether foetus expresses D antigen. Can do this through amniocentesis or free foetal DNA from maternal blood

Question 17

What determines the risk of rhesus allo-immunisation?

Go through antenatal care of a woman with mild, moderate and high risk for Rhesus allo-immunisation

Answer 17

Antibody titre determines the risk

Low risk (titre less than 32) - antibody titre at each visit, deliver at 38 weeks
Moderate risk (titre 64 - 256) - antibody titre at each visit, U/S screening from 20 weeks looking at MCA peak systolic velocity (velocity increases in severe anaemia from hyperdynamic circulation), CTG from 32 weeks (becomes more reliable than MCA in late pregnancy), deliver at 38 weeks or earlier if signs of anaemia
High risk (titre above 512) - U/S screening from 17 weeks (insufficient antibody to cross placenta earlier than this), foetal blood sampling if MCA PSV is increased (check Hb), intrauterine blood transfusion if anaemia proven (use purified RBCs from mother - won’t have antigens for antibodies to attack)

Question 18

How does anti-D work in prevention of allo-immunisation? When should it be administered and how quickly?

Answer 18

Passive anti-D antibody binds to D-antigens on foetal RBCs, preventing host antibodies from binding and initiating immune-mediated haemolysis of RBCs

Administer anti-D to Rh-negative women during:
28 and 34 weeks (prophylactic)
Sensitising events - bleeding (miscarriage, APH), trauma, post-delivery. Aim for within 72 hrs of the event

Question 19

What test can you do to estimate how much anti-D to give someone?

Answer 19

Kleihauer test - estimates volume of feto-maternal haemorrhage