TEACHING

S TI SPECIFIC LEARNING METHOD

NO ME OBJECTIVES CONTENT ACTIVITITI AV OF
ES AIDS EVALUATION

RH - INCOMPATIBILITY
INTRODUCTION:
DEFINITION:
Rh incompatibility:
Rh incompatibility is a condition that develops when
a pregnant woman has Rh-negative blood and the baby
in her womb has Rh-positive blood.
Isoimmunization:
Alloimmunization (isoimmunization) is defined as a
production of immune antibodies in an individual in
response to foreign red cell antigen derived from
another individual of the same species provided the first
one lacks the antigen. It occurs in two stage: 1
sensitization and 2 Immunization. This is in contrast to
ABO groups, where there are naturally occurring
isoimmune anti-A and anti-B antibodies.

METHODS
1) Transfusion of mismatched blood:
 In ABO group incompatibility, there are
naturally occurring anti-A and anti-B
isoagglutinins, which result in immediate
 adverse reaction.
 In case of Rh group there is no such
naturally occurring antibody and as such
there is no immediate reaction but the red
cells carrying the Rh antigen sensitize the
immunologically competent cells in the
body, provided the amount is sufficiently
large.
 This takes at least 1 week. Following a
subsequent exposure to the antigen, the
cells are stimulated to produce more
specific anti-d antibody.
 The Women may suffer a severe hemolytic
reaction to the subsequent mismatched
transfusion.
2) As a result of pregnancy (Rh-negative woman
bearing a Rh-positive fetus) normally the fetal
red cells containing the Rh antigen rarely enter
the maternal circulation.
 The following are the rare conditions where the
risk chance of fetomaternal bleed is present;
miscarriage. MTP, genetic aminocentesis,
embryoreduction, ectopic pregnancy,
hydatidiform mole, CVS cardocentesis, placenta
previa with bleeding, placental abruption, IUFD
external cephalic version abdominal trauma and
the delivery of a Rh-D positive infant to a Rh
negative mother.
 This is much more likely to occur during third
 stage of labor and following cesarean section or
manual removal of placenta. However recent
studies show a continuous fetometernal bleed
occurring throughout normal pregnancies (1%).
 The affection of the baby due to Rh
incompatibility is low considering the increased
number of Rh-positive babies delivered to Rh-
negative mothers:

THE REASONS FOR RH INCOMPATIBILITY:

 Insufficient placental transfer of fetal antigens or
maternal antibodies.
 Inborn inability to respond to the Rh antigen
stimulus.
 Immunological nonresponder – as found in 30%
of Rh-negative women
 ABO Incompatibility: has a protective effect
against the development of Rh sensitization. This
protective effect is significant when the mother is
type O and the father is Type A, B or AB, the
reasons are (i) ABO incompatible fetal cells are
cleared from the maternal circulation rapidly
before they are trapped by spleen (ii) maternal
anti-A or anti-B antibodies damage the Rh-
antigen so that it is no longer immunogenic.
 Variable antigenic stimulus of the D antigen
which depends on the Rh genotype of the fetal
blood eg:CDe/cde genotype.
 Volume of fetal blood entering into the maternal
 circulation (0.1 mL is considered as critical
sensitizing volume)
MECHANISH OF ANTIBODY FORMATION IN
THE MOTHER:
 If the ABO compatible (Mother and fetus have
the same ABO group or when the fetus is group
“O”), Rh-positive fetal red cells enter mothers’
blood, they remain in the circulation for their
remaining lifespan.
 Thereafter, they are removed from the circulation
by the reticuloendotheial tissues and are broken
down with liberation of antigen. The antibody
production is related not only to the
responsiveness of the reticuloendothelial system.
 But also to the amount of Rh antigen liberated
therefore to the number of red cells that have
entered the maternal blood. Because this takes a
long time, immunization In a first pregnancy in
unlikely.
 Detectable antibodies usually develop after 6
months following larger volume of fetomaternal
bleed. But if the fetomaternal bleed is less than
0.1 mL, the antibody may not be detected until
boosted by further Rh stimulus. Antibodies once
formed remain throughout life.
MANIFESTATIONS OF THE HEMOLYTIC
DISEASE OF THE FETUS AND NEWBORN
(HDFN):
Clinical manifestations of the hemolytic disease of the
fetus and newborn are:
 Hydrops fetalis
 Icterus gravis neonatorum
 Congenital anemia of newborn
Hydrops fetalis:
 This is the most serious form of Rh hemolytic
disease(HDFN). Exclusive destruction of the fetal red
cells leads to serve anemia, tissue anoxemia and
metabolic acidosis. These have got adverse effects on
the fetal heart and brain and on the plancenta.
 Hyperplasia of the placental tissue occurs in an effort
to increase the transfer of oxygen but the available
fetal red cells (oxygen carrying cells) are
progressively diminished due to hemolysis.
 As a result of fetal anoxemia there is a damage to the
liver leading to hypopproteinemia which is
responsible for generalized edema (hydrops fetalis)
ascites and hydrothorax. Fetal death occurs sooner or
later due to cardiac failure. The baby is either
stillborn or macerated and even if born alive, dies
soon after.
 The following are the diagnostic features:
 Mother is Rh-negative;
 serological examination reveals presence
of Rh-antibody
  there may be presence of Polyhydramnios
 Previous history of affection of a baby due
to hemolytic disease;
 Sonography: ( real time combined with
pulse Doppler) to detect edema in the skin,
scalp and pleural or pericardial effusion
and echogenic bowel;
 Straight X-ray abdomen showing Buddha
position of the fetus with a halo around the
head due to edematous scalp
 The baby at birth looks pale and edematous
with an enlarge abdomen due to ascites.
There is enlargement of liver around spleen
and
 Placenta is large, pale and edematous with
fluid oozing from it. The placental weight
may be increased to about half or even
almost equal to the fetal weight. There is
undue persistence of Langhans layer with
marked swelling of the villi. If the fetus is
not hydropic, the placenta usually looks
normal
Icterus gravies neonatorum:
 This clinical entity is the effect of lesser from of
HDFN. The baby is born alive without evidence
of jaundice but soon develops it within 24 hours
of birth.
 While the fetus is in-utero, there is destruction of
fetal red cells with liberation of unconjugated
 billirubin, which is mostly excreted through the
placenta into the maternal system.
 A portion of the billirubin enters the amniotic
fluid perhaps from the fetal lung or through the
skin or across the surface of the placenta or cord.
This is the reason why baby is not born with
jaundice.
 But as soon as the umbilical cord is clamped.
With continuing hemolysis, the bilirubin
concentration in increased. Sooner or later the
baby becomes jaundiced. The liver particularly of
a premature baby fails to conjugate the excessive
amount of bilirubin to make it soluble and
nontoxic.
 If the bilirubin rises to the critical of 20 mg per
100 mL (340 mol/L), the bilirubin crosses the
blood-brain barrier to damage the basal nuclei of
the brain permanently producing the clinical
manifestation of kernicterus.
Congenital anemia of the newborn:
 This is the mildest form of the disease where
hemolysis is going on slowly. Although the
anemia of red cells continues up to 6 week after
which the antibodies are not available for
hemolysis.
 The liver and spleen are enlarged, the sites of
extramedullary erythropoeisis
Affection of the mother: the impact of the Rh
incompatibility mainly falls on the baby. The
 mother may also be affected somewhat. There is
increased incidence of
 Preeclampsia
 Polyhydramnios
 Big size baby with its hazards
 hypofibrinogenemia due to prolonged
retention of dead fetus in uterus
 Postpartum hemorrhage due to big
placenta and blood coagulopathy
 Maternal syndrome – the salient features
are generalized edema, proteinuria and
pruritus due to cholestasis. These features
are ominous indicating imminent fetal
death in utero.
ANTENATAL INVESTIGATION PROTOCOL OF
RH- NEGATIVE MOTHERS:

Amniocentesis:
Amniocentesis and estimation of bilirubin in the
amniotic fluid by spectrophoto metry are indicated in:
 Antibody titer rises more than 1:8 to
determine whether the particular baby will be
affected or not;
 Previous history of severely affected baby
and
 Father is heterozygous to determine whether
the particular baby will be affected or not. As
such, if Rh antibodies are found in the current
pregnancy, it is an essential procedure to
 guide the management.
Selection of time:
 No history of previously affected baby-it is done
at 30-32 weeks and a second test should be
repeated after 3-4 weeks;
 Positive history of previously affected baby-it
should be done at least 10 weeks prior to the date
of previous stillbirth or other hemolytic
manifestations on the baby. However. it is useless
to perform prior to 20 weeks. 
Inference:
 The optical density of the liquor containing the
bilirubin pigment, is observed at 250 700nm
wavelength. The optical density difference at 450
nm wavelength gives the prediction of the
severity of fetal hemolysis.
 In presence of bilirubin, there is a “deviation
bulge" peaking at 450 nm wavelength. The bigger
the deviation bulge, the more severe is the
affection of the baby.
 For any given period of gestation, the height of
the spectrophotometric “deviation bulge” at
AOD450 falls within one of the three zones when
plotted in Liley’s chart . 
Predictions: 
 Liley’s zone I (low zone): The fetus is unlikely
to be affected and the pregnancy can be continued
to term. 
 Liley‘s zone ll (mid zone): Repeat amniocentesis
 by 2 weeks -> value upward -> cordocentesis ->
hematocrit < 30% -> intrauterine transfusion to
raise hematocrit 40-45%. Preterm delivery may
be needed after 34 weeks. 
 Liley’s zone IIl (high zone): The fetus is
severely affected and death is imminent.
Pregnancy > 34 weeks -> delivery. Pregnancy
<34 weeks -> cordocentesis -> hematocrit < 30%
-> intrauterine transfusion to raise hematocrit 40-
45%. Preterm delivery may be needed after 34
weeks.
Advantages:
 Spectrophotometric analysis when plotted in
relation to the Liley’s zone can predict with
fair degree of accuracy, the degree of hemolytic
process in the fetus. This can give indications
when to terminate the pregnancy and when to
give intrauterine fetal transfusion. 
PLAN OF DELIVERY:
EXCHANGE TRANSFUSION IN THE
NEWBORN:
PREVENTION OF Rh-IMMUNIZATION
To prevent active immunization
To prevent or minimize fetomaternal bleed
To avoid mismatched transfusion
To prevent active immunization:
 To prevent active immunization of Rh-negative
yet unimmunized, Rh anti-D immunoglobulin
(IgG) is administered intramuscularly to the
 mother following childbirth.
 The other conditions that the Rh anti-D
immunoglobulin should be given are mentioned
before.
Mods of action
 Is antibody mediatcd immune suppression
(AMIS). The possible mechanisms are: (i) the
anti-D antibody when Injected. blocks the Rh
antigen of the fetal cells.
 The intact antibody coated fetal red cells are
removed from the maternal circulation by the
spleen or lymph nodes
 Central inhibition – the fetal red cells, coated
with anti D antibodies interfere the production of
IgG from the B cells
When to administer?
 It should be administered within 72 hours or
preferably earlier following delivery or abortion.
 It should be given provided the baby born is Rh-
positive and the direct coombs’ test is negative in
case, where the specified time limit is over (>72
hours), she may be given up to 14-28 days after
the delivery to avoid sensitization.
 Similarly When the Rh factor of the fetus cannot
be determined, it should be administered without
any harm.
Dose:
 Anti D gammaglobulin is administered
intramuscularly to the mother 300 mg following
 delivery. All Rh –negative women should receive
50Mg of Rh-immune globulin IM within 72 hours
of induced or spontaneous abortion, ectopic or
molar pregnancy or CVS in the first trimester.
 Women With pregnancy beyond 12 weeks should
have full dose of 300mg. . Generally 300 mg dose
will protect a Woman from fetal hemorrhage of
upto 30 mL of fetal whole blood. ‘
Calculation of the dose:
 Approximate volume ol fetal blood entering into
the maternal circulation is to be estimated by
"Klelhauer-Betke test” using acid elution
technique to note the number of fetal red cells
(dark. refractile bodies) per 50 low power fields.
 If there are 80 fetal erythrocytes in 50 low power
fields in maternal peripheral blood films, it
represents a transplacental hemorrhage to the
extent of 4 ml. of fetal blood.
 More accurate tests are immunofluorescence and
flow cytometry.. If the volume of fetomaternal
hemorrhage is greater than 30 mL whole blood,
the dose of Rh immune globulin calculated is 10
us for every 1 ml. of fetal whole blood.
During pregnancy:
 In spite of postpartum Rh immune globulin
prophylaxis. failure rate is about 1- 2%. This is
due to antepartum fetomaternal hemorrhage and
sensitization (1-2%). if the woman is Rh negative
and has no antibody, she should have one dose of
 300 Mg Rh immune globulin as prophylaxis at
around 28 weeks (ACOG-1999) and again after
birth (within 72 hours).

To prevent or minimize fetomaternal bleed:

 Precautions during cesarean section: to prevent

blood spilling into the peritoneal cavity. (ii)
Manual removal of placenta should not be done
as a routine.
 Proplylactic ergometrine with the delivery of the
anterior shoulder should preferably be withheld,
as it may facilitate more fetoplacental bleed.
 Amniocentesis should be done after sonographic
localization of the placenta to prevent its injury
 Forcible attempt to perform external version
under anesthesia should be avoided.
 Manual removal of placenta should be done
gently.
 To refrain from abdominal palpation as far as
possible in abruptio placentae.
TO AVOID giving Rh-positive blood to one Rh-
negative female from her birth to the menopause. All
such women including women with multiple pregnancy
may need more than usual 300 Mg of anti-D
immunoglobulin.