Mudaliar

and
Menon’s
Clinical
Obstetric
s
13TH EDITION
Chapter 28
RH-
ISOIMMUNISATI
ON
 The RBCs carry a number of surface
antigens, antigens—C, c, D, d, E and e
These are collectively called the Rh factor
and inherited from both parents
If the individual has not inherited even a
single D, he/she is Rh-negative
Rh incompatibility is an immunological
INTRODUCT disorder wherein the mother produces
ION antibodies against the blood group factor,
which is present in the red cells of the fetus,
but which she does not possess
The mother’s immune system produces
antibodies against the fetal cells; these cross
the placenta to destroy the fetal RBCs
The production of these Rh antibodies is
called Rh iso-immunisation

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 Caucasians: 15%

INCIDEN India: 5–10%

CE
Japanese: Very low

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FACTORS INFLUENCING
RH-ISOIMMUNISATION
During pregnancy In labour
• Following spontaneous and therapeutic • Cesarean section
miscarriages • Manual removal of the placenta
• Ectopic pregnancy • Massage of the uterus
• Molar pregnancy • Early ligation of the cord
• Pre-eclampsia/eclampsia • Use of ergometrine, which may
• Antepartum hemorrhage squeeze the fetal cells into the maternal
• Multiple pregnancy circulation
• Invasive procedures such as chorion villus
sampling, amniocentesis and cordocentesis
• External cephalic version
• Fetal demise and maternal trauma
• ABO incompatibility between the mother and the
fetus protects against Rh-isoimmunisation

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 The critical sensitising volume that
QUANTUM can trigger isoimmunisation is 0.25
OF
TRANSPLACE mL.
NTAL In the first and second trimesters,
HEMORRHAG the amount of bleeding is always less
E than 0.1 mL.
The risk of immunisation is 3% with
0.1 mL of fetal red cells, 25% with
0.25–1 mL and increases to 65% with
more than 5 mL.

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MECHANISM OF RH
ISOIMMUNISATION
Primary immune response

Maternal Removed by
Fetal Rh +ve
circulation – reticuloendothelial
RBC
120 days system

Immune
Antigens
system: IgM
released
Ab, IgG Ab

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MECHANISM OF RH
ISOIMMUNISATION
Secondary immune response

Primary
Second dose Strong sharp
immune
of Ag rise of IgG
response

Crosses
placenta

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PATHOGENESIS OF
HEMOLYTIC DISEASE OF
THE FETUS AND THE
NEWBORN (HDFN)
Effect on the fetus
Erythroblastosis fetalis
Fetal anemia
Hydrops fetalis and stillbirth
Severe hemolysis: Extra-medullary erythropoiesis,
resulting in hepatosplenomegaly and portal
obstruction, hydrothorax and cardiac failure
Mild to moderate anemia: Severe jaundice and
kernicterus after birth
The placenta is pale and edematous with swollen
villi

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 EFFECT ON THE
NEWBORN
Excess unconjugated
bilirubin—crosses the
blood–brain barrier—
kernicterus
Cerebral irritation,
convulsions, twitching
and spasticity and
difficulties with fine
motor skills

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 METHODS TO IDENTIFY
FETOMATERNAL HEMORRHAGE
DURING PREGNANCY
1. Kleihauer acid elution technique:
When a blood smear is exposed to
a pH of 3.3 (by adding acid citrate
phosphate buffer), adult
hemoglobin elutes from the red
cells, leaving behind non-staining
‘ghost’ cells
Fetal hemoglobin does not elute
from red cells at this pH
Decide the dose of anti-D
immunoglobulin to be given
100 μg of anti-D would be required
to neutralise this 4 mL of FMH

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2. Rosetting test: Rh-positive cells coated with
antibodies form rosettes when Rh-positive
indicator cells are added

3. Flow cytometry: Alternative method

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 Indirect Coombs test
Known Rh-positive red cells are incubated
with the serum to be tested for Rh antibody
—agglutination of incubated red cells
If antibody titration is required—serial
dilution
METHODS TO
ASSESS THE
PRESENCE OF Direct Coombs test
RH ANTIBODIES Cord blood with fetal RBCs is mixed with
Coombs serum
If the fetal RBCs are already coated with
anti-D antibodies, agglutination occurs

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Postpartum prophylaxis
Since the amount of fetal blood entering the maternal circulation is usually not more than 15
mL, a dose of 300 μg of anti-D immunoglobulin can be given to neutralise the cells within 48–72
hours of delivery

Antepartum prophylaxis
A dose of 300 μg IM at week 28
Repeat dose within 72 hours after delivery of an Rh-positive infant
First-trimester pregnancy wastage: A dose of 50 μg
Second-trimester miscarriage: A dose of 300 μg of Rh anti-D immunoglobulins
Amniocentesis: 300 μg of anti-D immunoglobulin is given IM
Antepartum hemorrhage: Amount of fetomaternal hemorrhage by flow cytometry or Kleihauer
test; 300 μg of anti-D immunoglobulin for every 30 mL of fetal whole blood or 15 mL of fetal RBCs

PREVENTION OF RH-
ISOIMMUNISATION
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 Manageme
nt of Rh-
Negative
Non-
Immunised
Woman

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 Managem
ent of Rh-
negative
Isoimmuni
sed
Woman

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 1. Rh antibody titre
Critical titre: 1:16 or 1:32; risk of fetal
hydrops

2. Actual antibody levels

NON- <4 IU/mL: Fetal hemolysis is mild
INVASIVE 4–8 IU/mL: Moderate hemolysis; delivery by
METHODS 38 weeks of gestation
>8 IU/mL: Severe hemolysis–immediate
intervention with either intrauterine
transfusion or preterm delivery depending on
the gestational age

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 3. Ultrasound evaluation of the fetus
Early signs of fetal anemia
Hepatosplenomegaly
Polyhydramnios
Increase in umbilical and intrahepatic portal
vein diameter
NON- Large placenta
INVASIVE
Late findings of fetal anemia
METHODS
Pleural and pericardial effusions
Enlargement of heart
Scalp edema
Increased skin thickness

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 Doppler velocimetry of
umbilical and portal vein
shows ‘saw-toothed’
pattern—anemia
Middle cerebral arterial
Doppler shows a value
above 1.5 MOM—anemia

Hydrops fetalis

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1. Amniocentesis and the examination of amniotic
fluid
A rising or plateauing trend of OD values that reaches
the 80 percentile of zone two on the Liley curve or
enters the intrauterine transfusion zone of the Queenan
curve necessitates investigation by fetal blood sampling
Zone I: The baby is either unaffected or mildly affected INVASIVE
and can be allowed to go to term METHODS TO
Zone II: The baby can be allowed to develop in utero ASSESS THE
until 34 weeks of gestation SEVERITY OF
FETAL ANEMIA
Zone III: The fetus is severely affected, and intrauterine
death is imminent; Immediate delivery/intrauterine
transfusion

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Modified Liley
chart used to
determine the
appropriate
management
of an
isoimmunised
patient

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2. Fetal blood sampling
Cordocentesis
3. Intrauterine transfusion
Between 18 and 34 weeks
If the fetal hemoglobin concentration
reduces before 34 weeks (below 10 g/dL)
fetal transfusion is indicated
This is done under ultrasound guidance

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DELIVERY
Immunised fetus >34 weeks–delivered
<34 weeks–intrauterine transfusion is performed, and the fetus is delivered depending on
the severity of hemolysis

MANAGEMENT OF THE NEWBORN

Exchange transfusion is required in the following situations:
When the cord blood hemoglobin is <10 g/100mL
When the serum bilirubin level is >5 mg/100 mL
Obvious clinical erythroblastosis
The amount of blood removed is more than the amount of blood transfused
Type O Rh-negative blood is usually used for transfusion.

Advantages: Excess bilirubin is removed, antibodies acquired from the mother are removed
and anemia gets corrected
Adjuvant phototherapy and treatment with phenobarbitone may also be required

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