Rhesus Disease

Question 1

What is rhesus disease, what is the major consequence of rhesus disease

Answer 1

Development of rhesus antibodies in a rhesus negative mother after exposure to Rh +ve RBCs.
Mismatch between the foetus and mother can mean that when foetal red cells pass across to the maternal circulation (as they do in pregnancy) sensitisation of the maternal immune system to these foetal ‘foreign cells’ may occur and cause haemolytic disease of the foetus and newborn (HDFN).

Question 2

How many rhesus antigens are there, which are clinically significant

Answer 2

• There are 40 Rhesus antigens, the most clinically important being C, D and E (coded on two adjacent genes on chromosome 1)
• In practice only anti-D and anti-C cause HDFN

Question 3

What proportion of people in the UK are RhD negative

Answer 3

15% of the Caucasian population in the UK (lower in all other ethnic groups)

Question 4

Describe the pathophysiology of HDFN

Answer 4

Occurrence of HDFN involves three stages:
* A rhesus-negative mother must have conceived a baby who has inherited the rhesus-positive phenotype from the father
* Foetal cells must gain access to the maternal circulation sufficient to provoke a maternal antibody response (sensitising event)
* Maternal antibodies must cross the placenta and cause immune destruction of red cells in the foetus (subsequent pregnancy)

Rhesus disease does NOT affect the first pregnancy because the primary immune response is usually weak and consists mainly of IgM which does NOT cross the placenta (HDFN usually provoked by IgG response)

Question 5

What are some potentially sensitising events

Answer 5

• Amniocentesis, chorionic villus biopsy and cordocentesis , In-utero therapeutic interventions
• Antepartum haemorrhage/ uterine (PV) bleeding in pregnancy
• ECV
• Abdominal trauma (sharp/blunt, open/closed)
• Ectopic pregnancy, evacuation of a molar pregnancy
• Intrauterine death and stillbirth, miscarriage, threatened miscarriage, therapeutic termination of pregnancy
• Delivery – normal, instrumental or Caesarean section

Question 6

Investigations for rhesus status

Answer 6

• Blood sample should be taken for the routine antenatal 28-week blood group and antibody screen
• Kleihauer test- Shows the proportion of foetal cells present in the maternal sample- allows calculation of the amount of extra anti-D required (staining of foetal cells and ‘ghosting’ of maternal ones- count manually)

Question 7

How can rhesus disease be prevented antenatally

Answer 7

• ALL RhD-negative women who have not been previously sensitised should be offered routine antenatal prophylaxis with anti-D either with a single dose regimen at 28 weeks or a two-dose regimen at 28 and 34 weeks.
• Pregnant RhD-negative women with no immune anti-D should be offered prophylactic anti-D Ig within 72 hours of potentially sensitising events (some protection is still given if anti-D Ig is given up to 10 days after the sensitising event.)
• < 12 weeks= 250IU (ONLY TOP, ectopic, molar, heavy or repeated vaginal bleeding), 12-20 weeks= 250IU, 20+ weeks= 500IU alongside Kleihauer test

Question 8

How can rhesus disease be prevented postnatally

Answer 8

• A cord blood sample should be tested to obtain ABO and Rh D type of the baby.
• If the baby’s blood group is D positive, a minimum of 500 IU anti-D Ig should be administered to previously non-sensitised D negative women, within 72 h of the delivery, regardless of routine antenatal prophylaxis or prophylaxis following potential sensitisation
• Direct antiglobulin test (DAT) should be performed if HDN is suspected
• If there is an intrauterine death (IUD) and hence no sample can be obtained from the baby, prophylactic anti-D Ig should be administered to D-negative, previously non-sensitised women (500 IU)