Allo-immunisation Flashcards
What is the basic process behind alloimmunisation?
Mother is exposed to an antigen. Mother produces an antibody. Antibody crosses placenta, leading to foetal sequelae
What is the difference between maternal auto-antibodies and maternal allo/iso-antibodies?
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)
Name 3 diseases associated with maternal auto-antibodies
Thyroid auto-immune disease
Connective tissue disease (SLE, Sjogren’s)
ITP
Name 3 diseases associated with maternal allo-antibodies
Red cell allo-immunisation
Perinatal allo-immune thrombocytopaenia
Perinatal allo-immune neutropenia
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)?
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)
What proportion of pregnancies will have red cell allo-immunisation? What is the most common RBC allo-antibody?
1% - most common is anti-D
What proportion of people with RBC allo-immunisation will develop mild, moderate and severe symptoms? What symptoms are indicative of each level of severity?
Mild - 50% (mild haemolysis = mild jaundice).
Moderate - 25% (severe jaundice, mild anaemia).
Severe - 25% (severe anaemia, hydrops, FDIU).
What is a consequence/sequelae of severe jaundice in a neonate?
In severe jaundice, bilirubin can cross the blood-brain barrier = brain damage (kernicterus)
What is foetal hydrops?
Congestive cardiac failure in a foetus from severe anaemia, leading to generalised oedema (ascites, effusions) and potentially FDIU
What is primary immunisation (in context of allo-immunisation)? Name 2 mechanisms through which can happen
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)
Name 4 ways that feto-maternal haemorrhage can occur
Bleeding (abortion, ectopic, APH, miscarriage)
Trauma (CVS, amniocentesis, blunt trauma)
Delivery
Occult (spontaneous)
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?
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
What do you do in relation to allo-immunisation for all women in the first antenatal visit?
Take blood type, and screen for existing anti red cell antibodies (1% of population)
What proportion of women are Rh-negative?
15%
If a woman is Rh-negative, what 2 things should you check in relation to allo-immunisation in the first antenatal visit?
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)
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
Take foetal DNA to see whether foetus expresses D antigen. Can do this through amniocentesis or free foetal DNA from maternal blood
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
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)
How does anti-D work in prevention of allo-immunisation? When should it be administered and how quickly?
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
What test can you do to estimate how much anti-D to give someone?
Kleihauer test - estimates volume of feto-maternal haemorrhage