1. Dr. ARMAA A. AL SANJARY DEP.OBST.&GYN.
RH -ALLOIMMUNIZATION
Dr. ARMAA A. AL SANJARY
DEP.OBST.&GYN.

2. The Rh factor (ie, Rhesus factor) is a red blood cell
surface antigen. Rhesus family include these
antigen D ,C ,E ,d ,c ,e .
A person is Rh-positive if they possess the D allele
and Rh negative if it is absent .
Rh isoimmunization: is an immunological condition
that occurs in a pregnant , Rh-negative patient
carrying an Rh positive fetus .

3. The incidence of Rh –ve individuals varies
by race .In north america caucasian ,the
incidence of Rh –ve genotype is 15%.
Alloimmunization may occur to other antigen
As Kidd antigen and less common as Kell,
and Duffy

4. Rh antigen is inherited as two set of three
alleles ,each seat is Inherited from one parent.
These alleles are : Cc,Dd,Ee,
An individual may be homozygous or hetero-
ozygous for each of these alleles.
The presence of the D antigen determines
whether an individual is Rh positive or negative.
Individual genotype can be directly determined by
Polymerase chain reaction technology.

5. Alloimmunization of the Rh negative mother
to the fetal Rh positive antigen occurs by :
Transplacental fetal to maternal haemorrhage (most common).
most commonly after delivery (90%) and may be
after abortion , trauma in pregnancy ,obstetric
procedure .
Heterologous blood transfusion (second common).

6. Type of immune response to the D antigen
Primary immune response occurs over six
weeks to twelve months ,weak response ,
predominantly of IgM ,1st pregnancy is not
affected by haemolysis.
The secondary immune response is rapid ,
IgG .

7. Once maternal Rh immunoglobulin G (IgG) antibodies are produced ,they may cross freely
from the placenta to the fetal circulation, where
they form antigen-antibody complexes with Rh-
positive fetal erythrocytes and eventually are
destroyed, resulting in a fetal alloimmune
hemolytic anemia.
Although the Rh blood group systems consist of
several antigens (D, C, c, E ,e), the D antigen is the
most immunogenic; therefore , it most commonly is
involved in Rh Incompatibility .

8. All the sequelae of Rh alloimmunization are
the result of haemolytic anaemia and may
develops slowly or rapidly .
There is :
Anemia
-Raise in the retic count .
-Erythroblastosis (nucleated RBC are released into the circulation) .

9. Hyperbilirubinaemia : all the bilirubin in the fetus is indirect ,the albumine unbound
fraction may penetrate the lipid neuronal
membrane cause cell death ,development
of encephalopathy (kernicterus) ,profound
neurosensory deafness ,and chorioathetoid
spastic cerebral palsy in survivors.

10. Hydrops fetalis result from :
-Hb deficit .
-portal hypertension Liver and spleen are enlarged
because of extramedullary hematopoiesis and
congestion.
-Hypoalbuminaemia secondary to liver dysfunction.
-Cardiac dysfunction .

11. The incidence of Rh alloimmunization has
declined dramatically due to :
Immunoprophylaxis
smaller families .

12. Management of Rh negative unsensitized women during pregnancy :
The patient should have two records of blood group and Rh that are in agreement.
Test the father if Rh positive or negative .
Rh positive father could be homozygous
and all the off spring will be Rh positive.
if he is heterozygous there is 50% chance
that the fetus will be Rh negative .
if the father is Rh negative nothing should
be done.

13. Indirect coombs test performed at booking ,
and repeated at monthly intervals from 18-
20 weeks to predict sensitization .
level < 1:4 is unsensitized.
Cover any potential sensitizing event during pregnancy as vaginal bleeding or trauma during pregnancy with Anti-D immunoglobulin
50 microgram (250 IU) before 22 weeks.
100 microgram (500 IU) after 22weeks

14. Anti-D immunoglobulin prophylaxis should be
administered to all non sensitized Rh –ve
women at 28 weeks gestation.
At delivery cord blood is obtained to determine the neonatal ABO and Rh type and direct coomb’s test to detect antibody attached to the fetal RBC.

15. Anti-D immunoglobulin 300 microg should
be administered to the mother to prevent
maternal sensitization to < 30 ml of fetal
Rh positive blood .
Larger dose of Anti -D immunoglobulin
should be given in cases of larger fetal to
maternal haemorrhage ,such as in cases of
C.S. ,manual removal of the placenta ,
trauma ,APH, IUD ,twin .

16. Maternal blood is screened by Kleihauer -
Betke test to assess the volume of fetal to
maternal haemorrhage.
The maternal blood is fixed on a slide by ethanol and treated with citrate phosphate buffer which
readily remove the adult HB but not the fetal Hb .
After staining the fetal cells can readily distinguished
and counted from the empty maternal cells.
N. of fetal cells = X
N. of maternal cells estimated maternal blood vol.(ml)
X : is the estimated fetal blood volume

17. Management of sensitized Rh negative women :
Non – invasive evaluation :
We should predict the fetal risk in this pregnancy by :
Past obstetric history : the magnitude of fetal
and neonatal disease typically progress
from one pregnancy to another .
Maternal indirect coombs antibody titer ,should be
assessed monthly ,there is a critical titer below
which sever haemolytic disease does not occur
and any invasive fetal monitoring is deferred until
the critical titer is exceeded .

18. level <= 1:32 should be followed by non invasive method
level <= 1:32 should be followed by non invasive method . Level >= 1:64 should be followed by invasive method
In subsequent pregnancies once the threshold
is crossed ,titer and history are inadequate
measures upon which to base management.
PCR is used to determine the fetal genotye
and whether the fetus is antigen positive .
Rh negative baby obviate the need for further
follow up.

19. High resolution ultrasonography for
monitoring of the fetus to predict haemolytic anemia and hydrops ,amniotic fluid volume,
liver and spleen length and thickness,
placental thickness, cardiac biventricular thickness ( not proven to be reliable ).
Doppler blood flow velocities used for screening for fetal anemia.

20. Invasive evaluation:
Tow invasive methods are used to search for
fetal anemia secondary to haemolytic disease after
the indirect coombs test exceed the local threshold.
These are :
Indirect : spectrophotometry ( delta OD 450)
on amniotic fluid sample gained by ultrasound guided
technique (amniocentesis).
PCR to detect the blood group and Rh of the fetus .
Direct : fetal blood studies by cordocentesis.
Hb , Bd group and Rh, retics ,serum bilirubin,
serology (direct coombs test) .
The method chosen depend on facility available
and doctor experience .

21. By amniocentesis Liley observed that the
delta OD450 normally declined with advancing
gestational age (opposite to the bilirubin
concentration) .
The Liley’s chart is divided into 3 zones:
zone 1 :mild or no fetal disease.
zone 2 :moderate disease.
zone 3 :sever disease with the possibility of
fetal hydrops with in 7 days .

22. Amniocentesis repeated every 1-2 weeks
depending on the severity ,and intrauterine
fetal blood transfusion or delivery is decided
in zone 3 or with a progressive raise in the
upper zone 2 ,depending on the gestation
of pregnancy .

24. Treatment
Fetal intrauterine blood transfusion :
It’s the treatment of significant fetal haemolytic
anaemia prior to 34 week gestation .
Transfusion should be undertaken only if the
fetal haematocrit is below 30% or in hydrops.
We use blood compatible with the mother
and the fetus (O negative) ,fresh ,tested to
exclude infectious agents ,haematocrit of 70%.

25. There are two types of blood
transfusion :
Intraperitoneal transfusion .
Intravascular transfusion .

26. -Transfusion should be repeated every 3-4 weeks .
-There is no justification for routine preterm delivery
-The last transfusion should be performed at weeks and labour induced at weeks.
-Mode of delivery in non anaemic transfused fetus depend on obstetric indication .

27. Neonatal surveillance :
Infants received intrauterine transfusion
usually do well postnatally .
-Hyperbilirubinaemia can be managed by:
Phototherapy.
Double volume exchange transfusion.
-Neonatal small transfusion for correction
of anaemia