3.6 Haemolytic Disease of the Foetus and Newborn (HDFN)

Question 1

Mechanism
- Most common scenario – Rh D negative mother bearing Rh D positive foetus
o Red cells in the foetal circulation can cross the placenta into the maternal circulation at times of risks such as during pregnancy when there is shearing of the placenta

o The mother’s blood will recognise the Rh D antigens from the foetal Rh D positive RBCs, stimulating her immune system to form anti-D antibodies
o In this 1st pregnancy, the baby is unharmed and fine – exposure is very often during _________________

• During a 2nd pregnancy, the mother has anti-D antibodies that can _________________ as they are IgG antibodies
  o If the 2nd foetus is Rh D positive, the mother’s anti-D antibodies will coat the Rh D positive red cells in the foetus
  o Results in the destruction of the cells by the ______________________ and the foetus becoming anaemic
  o The degree of this depend on the several factors such as the level of the maternal antibodies but this can be very severe and even fatal
  o In less severe cases, it only affects the baby after birth

Answer 1

delivery or the 3rd trimester;

cross the placenta;

foetal reticuloendothelial system (spleen and liver)

Question 2

Clinical features of HDFN
- _______________– severe anaemia resulting in cardiac failure accumulation of fluid in cavities leading to ascites and pleural effusion
- ______________– high unconjugated bilirubin levels
exceed blood carrying capacity and is toxic to the foetal developing brain especially the basal ganglia

Answer 2

Hydrops fetalis ;

Kernicterus

Question 3

Potentially sensitising events – any traumatic event can sensitise a Rh D negative mother to a Rh D positive foetus

• Amniocentesis and chorionic villous sampling – amniocentesis is used primarily in prenatal diagnosis of __________________________
• Antepartum haemorrhage/ vaginal bleeding
• Abdominal trauma (falls and car accidents) – especially in the 3rd trimester due to larger amount of _____________________
• Ectopic pregnancies
• Miscarriages
• Termination of pregnancy
• Delivery – all methods

Answer 3

chromosomal abnormalities and foetal infections, as well as for sex determination;

foetal-maternal haemorrhage;

Question 4

Reduction of risk of HDFN
- Use of anti-D immunoglobulin given to mum – results in the coating of foetal red blood cells and removal by the _______________ before they can sensitise the mother’s immune system to produce anti-D antibodies
- ______________ prevent sensitisation to 1 ml of Rh D positive foetal red cells in foetal-maternal haemorrhage (FMH)
o 500 IU covers up to 4 mL foetal red cells and 1500 IU covers up to 12 mL
o Occasionally, more is needed if FMH is higher

Event IU of anti-D needed
- Before 20 weeks of pregnancy –> _______
- After 20 weeks of pregnancy –> ______
- A larger dose may be needed for larger bleeds especially in advanced pregnancies so size of FMH should be determined (by _______________________) for events after 20 weeks
- Anti-D is not required if the foetus is Rh D negative
o It is difficult to determine if a foetus is Rh D negative unless the father is known to be Rh -
o In most situations if the father is Rh D positive the child is assumed to be Rh positive too

• Anti-D does not work if ___________________
• To be effective – IM anti-D Ig should be given within 72 hours of the potentially sensitising event
• Routine antenatal anti-D prophylaxis (RAADP) – about 1% of pregnancies have no obvious ‘sensitising events’, yet Rh D negative mothers become sensitised
  o To prevent this, routine anti-D prophylaxis is given in the 3rd trimester – 500 IU at _________________ OR single 1500 IU dose between _____________________
  o The number of obstetric deaths due to HDFN in UK have dropped from 0.46 per 1000 in 1950 to <0.016 now

Answer 4

maternal reticuloendothelial system ;

125 IU (IM) ;

250;
500;

acid elution and/or flow cytometry;

the mother has already been sensitised (developed anti-D) in the past;

28 and 34 weeks;

28 to 30 weeks

Question 5

Other preventive measures against HDFN

• _________________ of all pregnant women – at 1st booking and again at 28 weeks to check for RBC antibodies
• Serial RBC antibody quantification if present
• Paternal typing
• Foetus monitoring – using _____________________

Other RBC antibodies – other alloantibodies may also cause HDFN

• The Rh system is complex with multiple alleles – other antigens include c, C and e,E (2 alleles)
• ___________________ can also cause severe HDFN
• The ABO antigen system does not cause severe HDFN – anti-B can theoretically cause HDFN, but they are mainly IgM (in the maternal circulation) and cannot cross the placenta
• IgG Anti-A and anti-B antibodies from group O mothers can cause HDFN, but this is usually mild because ___________________________
  o Many tissues express A and B antigens too – anti-A and B antibodies that cross the placenta bind to many places other than RBCs

Answer 5

Antibody screen;

Doppler ultrasound;

Anti-c and anti-Kell;

foetal RBCs express less of the A and B antigens than adult RBCs