Rhesus disease Flashcards
Define rhesus disease.
a.k.a. haemolytic disease of the fetus and newborn (HDFN)
= a condition which results from transplacental passage of maternal antibodies which cause immune haemolysis of fetal/neonatal red blood cells.
What are the two ways in which blood groups are defined? Which is most severely associated with severe haemolytic disease?
ABO group = A, B, O, AB
Rhesus system = C, D, E (most clinically important, but comprises >40 other antigens)
Rhesus system is the one most commonly associated with severe haemolytic disease
Other than anti-D, what other rhesus antibody causes HDFN?
Anti-D
Anti-c (small c) - but this is much less common than anti-D
Where are genes for the rhesus system encoded?
They are coded on two adjacent genes that sit within chromosome one.
Describe the inheritance patterns of rhesus system antigens.
On chromosome 1:
- One gene codes for antigen polypeptides C/c and E/e (where c is the allelic antigen of C and e is the allelic antigen of E)
- Other gene codes for the D polypeptide (rhesus antigen). The d (little d) antigen has not been identified so it is probable that women who are D negative lack the antigen altogether, as opposed to those with c or e alleic antigens.
Antigen expression is usually dominant, whereas those who have a negative phenotype are either homozygous for the recessive allele or have a deletion of that gene
What are the three steps of rhesus isoimmunisation?
- A rhesus-negative mother must conceive a baby who has inherited the rhesus-positive phenotype from the father.
- Fetal cells must gain access to the maternal circulation in a sufficient volume to provoke a maternal antibody response.
- Maternal antibodies must cross the placenta and cause immune destruction of RBC in the fetus.
Why does rhesus disease not usually affect the first pregnancy?
Even if there is a sensitisation event, the primary response is usually weak and consists primarily of IgM (cannot cross placenta)
Subsequent resensitisations will cause a much greater B-cell response with IgG which can cross the placenta into fetal circulation. If present in suffienct quantity then fetal heamolysis will occur.
Name 4 potential sensitising events for rhesus disease.
- Miscarriage
- Termination of pregnancy
- Antepartum haemorrhage
- Invasive prenatal testing (chorion villus sampling, amniocentesis and cordocentesis)
- Delivery
How common is rhesus disease? Is it more comon in certain populations?
15% of the UK caucaisan population is rhesus negative but two thirds of RhD -ve mothers would be expected to carry a RhD +ve child as 55% of men are Dd heterozygous.
Lower prevalence of RhD -ve in other ethnic groups
Rhesus disease is uncommon in UK but more common where anti-D prophylaxis is not widespread
How is the dosage of anti-D post-sensitising event determined?
The exact dose is determined by:
- the gestation at which sensitization has occurred
- the size of the feto-maternal haemorrhage using Kleihauer test of maternal blood
What is the Kleinhauer test?
Kleihauer test of maternal blood = determines the proportion of fetal cells present in the maternal sample.
It relies on the ability of fetal red blood cells to resist denaturation by alcohol or acid and it allows calculation of the size of the feto-maternal transfusion and the amount of extra anti-D Ig required.
What time frame within the sensitising event can anti-D be given?
- Ideally within 72 hours
- But can sometimes be given up to 10 days after the event
What is the management of sensitising events at different stages of pregnancy?
<12 weeks - Dose: 250 IU. Unlikely that sensitization would occur; anti-D only indicated after ectopic pregnancy, molar pregnancy, therapeutic TOP and in uterine bleeding where this is repeated, heavy or associated with abdominal pain.
12 and 20 weeks - Dose: minimum 250 IU within 72 hours + Kleihauer test done to check if further anti-D is necessary.
>20 weeks - Dose: minimum anti-D Ig dose of 500 IU within 72 hours pending Kleihauer test result. Further anti-D can be given if indicated by the Kleihauer test.
In practice, why is ABO incompatibility not usually a problem?
Most anti-A and anti-B antibodies are IgM so cannot cross the placenta
In addition, A and B antigens are not fully developed in the fetus
List some indications for prophylactic anti-D in the first trimester.
- ectopic pregnancy,
- molar pregnancy,
- therapeutic TOP
- uterine bleeding where this is repeated, heavy or associated with abdominal pain
Why is anti-D prophylaxis offered to all rhesus negative women, even without an obvious sensitising event in pregnancy? When is this offered?
A small number of Rhesus-negative women become sensitised in pregnancy despite no clinically obvious sensitising event
UK guidelines:
- Single dose at 28 weeks OR
- Two doses at 28 and 34 weeks
What are the signs of fetal anaemia? At what Hb do these become apparent?
Usually US/clinical fatures are not apparent unless fetal Hb is more than 5g/dL less than the mean for that gestation + not obvious until fetal Hb <6g/dL.
- Polyhydramnios
- Enlarged fetal heart
- Ascites and pericardial effusions
- Hyperdynamic fetal circulation (can be detected by Doppler ultrasound by measuring increased velocities in the middle cerebral artery or aorta).
- Reduced fetal movements.
- Abnormal CTG with reduced variability, eventually a ‘sinusoidal’ trace.
What pattern on CTG is characteristic of fetal anaemia?
‘Sinusoidal’ trace
What is the prognosis for subsequent pregnancies in rhesus-negative mothers who have been previously sensitised?
Worse outcomes with each pregnancy
How can hyperdynamic fetal circulation be detected in fetal anaemia?
Doppler ultrasound of middle cerebral artery or aorta - increased velocities of blood flow
What is the management of pregnant women who have been rhesus D sensitised in a prevoius pregnancy?
Sensitisation itself is irreversible
(1) If father is D-rhesus-negative - nothing; no risk that the baby will be rhesus positive.
(2) If father is D-rhesus positive or unknown NB: fetus may still be rhesus-negative if father is heterozygous
- Close monitoring of antibody levels every 2-4 weeks from booking
-
+/- if antibody levels rise –> examine fetus for anaemia
- MCA Dopplers peak velocity measurements correlate well with fetal anaemia
-
+/- if fetal anaemia present –> refer to tertiary fetal medicine centre
- Fetal blood transfusion once anaemia confirmed with blood sample OR
- Delivery
What are the routes of administration of fetal blood transfusion?
- Into the umbilical vein at point of cord insertion - ideally through placenta and not through amniotic sac
- Into the intrahepatic vein
- Into peritoneal cavity - not as effective
- Into fetal heart
What are the characteristics of blood given during fetal tranfusion?
Transfused blood is:
- RhD negative
- Crossmatched with a maternal sample.
- Densely packed (haemoglobin usually around 30 g/l) so that small volumes are used.
- WCC depleted and irradiated.
- Screened for infection including CMV
What is a useful side effect of fetal transfusion in HDFN?
Tansfusion –> suppress fetal erythropoiesis –> reduced oncentration of antigen-positive cells –> less cells available for haemolysis
