PRESENTATION DELIVERED BY 3RD YEAR MEDICAL STUDENTS AT ZIAUDDIN UNIVERSITY.

1. RHESUS
ISOIMMUNIZATION
OR RHESUS INCOMPATIBILITY
PREPARED BY:
UMER
SARMAD

2. INTRODUCTION
Rh incompatibility occurs when a woman who is
Rh-negative becomes pregnant with a baby with
Rh-positive blood. With Rh incompatibility, the
woman's immune system reacts and creates Rh
antibodies. These antibodies help drive an
immune system attack against the baby, which
the mother's body views as a foreign object.

3. ABO AND RHESUS SYSTEM*
The importance of these blood group systems is that a
mismatch between the fetus and mother can mean that when
fetal red cells pass across to the maternal circulation, as they do
to a greater or lesser extent during pregnancy, sensitization of
the maternal immune system to these fetal ‘foreign’ red blood
cells may occur and subsequently give rise to haemolytic
disease of the fetus and newborn (HDFN). The rhesus system is
the one most commonly associated with severe haemolytic
disease

4. THE ETIOLOGY OF RHESUS DISEASE
The rhesus system comprises at least 40 antigens, the most clinically
important of which are C, D and E.
They are coded on two adjacent genes that sit within chromosome
one. One gene codes for antigen polypeptides C/c and E/e while the
other codes for the D* polypeptide (rhesus antigen). 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. In practice only anti-D and anti-c regularly cause
HDFN and anti-D is much more common than anti-c.

5. Occurrence of HDFN as a result of rhesus isoimmunization
involves three key stages.
1. CONCEIVE
2. SENSITIZATION
3. DESTRUCTION

6. Rhesus disease does not affect a first pregnancy as the primary response is
usually weak and consists primarily of immunoglobulin (Ig) M antibodies* that do
not cross the placenta. However, in a subsequent pregnancy with a rhesus-
positive baby, rhesus-positive red cells pass from the baby to the maternal
circulation and cause maternal resensitization. On this occasion, the B-cells
produce a much larger response, this time of IgG antibodies that can cross the
placenta to the fetal circulation. If these antibodies are present in sufficient
quantities, fetal haemolysis may occur, leading to such severe anaemia that the
fetus may die unless a transfusion is performed.Rhesus disease is commonest in
countries where anti-D prophylaxis is not widespread, such as the Middle East
and Russia.

8. PREVENTING RHESUS ISOIMMUNIZATION
The process of isoimmunization can be prevented by the intramuscular
administration of anti-D immunoglobulins to a mother. Anti-D immunoglobulins
‘mop up’ any circulating rhesus-positive cells before an immune response is
excited in the mother. It is normal practice to administer anti-D as soon as
possible after any potential sensitizing events that may cause feto-maternal
haemorrhage and preferably within 72 hours of exposure to fetal red cells.
However, if, exceptionally, this deadline cannot be met, some protection may still
be offered if anti-D Ig is given up to 10 days after the sensitizing event. The exact
dose is determined by the gestation at which sensitization has occurred and the
size of the feto-maternal haemorrhage.

9. KLEIHAUER TEST
A Kleihauer test of maternal blood determines the amount of anti-D Ig
required. A small number of rhesus-negative women become sensitized
during pregnancy despite the administration of anti-D at delivery and without
a clinically obvious sensitizing event. The prophylactic anti-D would reduce
the risk of isoimmunization. Current UK guidelines suggest that all rhesus-
negative pregnant women who have not been previously sensitized should be
offered routine antenatal prophylaxis with anti-D, either with a single dose
regimen at around 28 weeks or a two-dose regimen given at 28 and 34
weeks of gestation.

12. THE MANAGEMENT OF RHESUS DISEASE IN A
SENSITIZED WOMEN
If father of the next baby is D-rhesus negative. In this situation there is no risk
that the baby will be D-rhesus positive and therefore there is no chance of
rhesus disease. The father of the next baby is D-rhesus positive. He may be
heterozygous and in this situation determining the paternal phenotype is
useful in anticipating the likely fetal phenotype and, thus, the potential for
development of HDFN.In a sensitized woman, if the father is D-rhesus
positive or unknown, standard management nvolves monitoring antibody
levels every 2–4 weeks from booking. If antibody levels rise, the baby should
be examined for signs of anaemia. Middle cerebral artery (MCA) Dopplers
(peak velocity measurement) have been shown to correlate reliably with
diagnosing fetal anaemia.

14. Treatment options include delivery or fetal blood transfusion. Delivery
of the fetus is an option if the fetus is sufficiently mature. However,
delivery of an anaemic, rapidly haemolysing premature baby is a
significant risk and should not be undertaken lightly. Delivery must
take place in a unit where adequate neonatal support and expertise is
available, and generally delivery should not be before 36–37 weeks’
gestation unless there are specific reasons such as special difficulty
with fetal blood transfusion

15. ROUTES OF FETAL BLOOD TRANSFUSION
Blood can be transfused into a fetus in various ways depending on the
gestation, the site of the cord insertion and the clinical situation. Routes of
administration include:
• Into the umbilical vein at the point of the cord insertion
• Into the intrahepatic vein.
• Into the peritoneal cavity (not as effective but some blood is absorbed and
this may be the only option, for example in early gestations).
• Into the fetal heart.

16. Transfused blood is:
• RhD negative.
• Crossmatched with a maternal sample.
• Densely packed (haemoglobin usually around 30 g/l) so that small volumes are used.
• White cell depleted and irradiated.
• Screened for infection including cytomegalovirus (CMV).

18. REFERENCE:
OBSTETRICS BY TEN TEACHERS 20TH EDITION