ALLOIMMUNIZATION IN

PREGNANCY
 Erythroblastosis Fetalis
(Red Cell Alloimmunization)
 the first description of erythroblastosis
fetalis (hemolytic disease of the newborn)
dates back to 1609
 until the early 1900s that the role of
alloimmunization in the pathogenesis of
erythroblastosis was established
 In the past, Rh alloimmunization also has
been referred to as Rh sensitization or Rh
isoimmunization.
ERYTHROBLASTOSIS FETALIS

3
 Genetics of the Rh Antigen
 three genetic loci, each with two major alleles,
lettered C, c, D, E, and e.
 The Rh gene complex is described by the three
appropriate letters with eight possible
combinations (listed in decreasing order of
frequency among whites): CDe, cde, cDE, cDe,
Cde, cdE, CDE, and CdE.
 Rh positive indicates the presence of the D antigen
 Rh negative indicates the absence of D antigen on
erythrocytes.
Pathophysiology of Rh Alloimmunization

Rh D alloimmunization can occur only in the

presence of three conditions:
(a) the fetus must have Rh-positive erythrocytes,
and the mother must have Rh-negative
erythrocytes;
(b) the mother must have the immunogenic
capacity to produce antibody directed against
the D antigen;
(c) a sufficient number of fetal erythrocytes must
gain access to the maternal circulation.
Incidence of Rh D Incompatibility and
Subsequent Alloimmunization
 About 10% of pregnancies are Rh incompatible
– fewer than 20% of Rh-incompatible pregnancies result in
alloimmunization
 About 16% of untreated Rh-negative women become
alloimmunized in their first Rh-incompatible (ABO-
compatible) pregnancy
– Half produce detectable anti-D antibody within 6 months of
delivery,
– rest have undetectable amounts until early in the next incompatible
pregnancy
 before the introduction of Rh immune globulin
prophylaxis, only about 1% of pregnant women had anti-D
antibody
 Maternal Immunologic Response:

 30% of Rh-negative individuals appear to

be immunologic “nonresponders”who will
not become sensitized
 ABO incompatibility diminishes the risk of
alloimmunization to about 1.5% to 2.0%
after the delivery of an Rh-positive fetus
– The effect is most pronounced if the mother is
type O and the father is type A, B, or AB.
 Fetomaternal Hemorrhage
 Fetal red cells may gain access to the
maternal circulation :
– during pregnancy,
– During delivery:
– the immediate postpartum period
Fetomaternal Hemorrhage

 During delivery :
– 15-50% of births
– The amount of fetal blood entering the maternal
circulation is usually less than 0.1 mL but may
be greater than 30 mL in 0.2% to 1.0% of cases.
 Fetomaternal Hemorrhage

 immediate postpartum period :

– Risk factors :
» cesarean delivery
» multiple gestations,
» bleeding placenta previa or abruption,
» manual removal of the placenta,
» intrauterine manipulation.
 However, the majority of cases of excessive
fetomaternal hemorrhage occur after
uncomplicated vaginal delivery.
 Rh D Immune Globulin and the
Prevention of Rh D Alloimmunization
 antibody-mediated immune suppression
 the amount of Rh D immune globulin necessary to
prevent alloimmunization varies according to the
size of fetomaternal hemorrhage:
– 300 µg of Rh D immune globulin for exposure to 10
mL of fetal blood
– 20 µg of Rh D immune globulin for exposure to 1 mL
of fetal erythrocytes
– 10 µg of Rh D immune globulin for 1 mL of whole
fetal blood
Postpartum Alloimmunization Prophylaxis

 administration of Rh D immune globulin

– a dose of 100 µg to 150 µg
– within 72 hours of delivery
Postpartum Alloimmunization Prophylaxis

 Rh D immune globulin should be given as soon as possible

after exposure to Rh D-positive blood (delivery or other
event associated with fetomaternal hemorrhage) and before
the primary immune response is established
 if for some reason Rh D immune globulin prophylaxis
does not occur within 72 hours after exposure, susceptible
Rh D-negative women should be treated up to 14 to 28
days.
 if the neonatal Rh status is unknown 3 days after delivery,
Rh D immune globulin should be given rather than waiting
for the neonatal results.
 Antepartum Alloimmunization
Prophylaxis
 Prophylactic administration of Rh D
immune globulin at 28 weeks gestation
reduces the incidence of alloimmunization
from 1.8% to 0.1%
 Management of the Unsensitized Rh-
Negative Pregnant Woman
 Every woman should have her ABO blood
group, Rh type, and antibody screen
checked at the first prenatal visit of all
pregnancies
 If she is Rh-negative or weak D-negative
and has no demonstrable antibody,
– she is a candidate for 300 µg Rh D immune
globulin prophylaxis at around 28 weeks
gestation and again immediately postpartum
 Management of the Unsensitized Rh-
Negative Pregnant Woman
 obtaining another antibody screen before
administration of Rh D immune globulin, in
 After delivery, another antibody screen is
routinely performed. If negative and the
newborn is Rh D positive or weak D
positive, women should be given 300 µg
of Rh D immune globulincluding
antepartum prophylaxis
 Management of the Unsensitized
Rh-Negative Pregnant Woman
 because a small number of deliveries (0.1%
to 1.0%) result in a fetomaternal
hemorrhage greater than 30 mL :
– a screen for “excessive” fetomaternal
hemorrhage should be performed routinely
» use the erythrocyte rosette test
 If positive :the volume of fetal red cells in the maternal
circulation can be calculated by using the Kleihauer-Betke
test ,if >30 ml :
– an additional 10 µg of Rh D immune globulin
should be administered for each additional milliliter
of fetal blood.
Management of the Unsensitized Rh-
Negative Pregnant Woman
 Management of the Unsensitized
Rh-Negative Pregnant Woman
 A weak D-“positive mother who delivers an
Rh-positive infant is not at significant risk
of Rh alloimmunization
 Occasionally, a woman previously typed as
Rh negative is unexpectedly found to be
weak D positive during pregnancy or after
delivery
– if fetomaternal hemorrhage is found :
» the mother should be treated with Rh D immune
globulin.
 Management of the Unsensitized
Rh-Negative Pregnant Woman
 First-trimester complications result in
fetomaternal hemorrhage sufficient to
alloimmunization :
– spontaneous miscarriage,
– elective abortion
– ectopic abortion
 women with threatened first-trimester
miscarriage
– only occasionally is associated with
alloimmunization
 Management of the Unsensitized
Rh-Negative Pregnant Woman
 patient who has antepartum bleeding or
suffers an unexplained second- or third-
trimester fetal death:
– should receive Rh D immune globulin
prophylaxis
– be evaluated for the possibility of massive
fetomaternal hemorrhage.
 Management of the Unsensitized
Rh-Negative Pregnant Woman
 Several procedures also may result in
fetomaternal hemorrhage sufficient to cause
alloimmunization :
– chorionic villus sampling (CVS)
– amniocentesis
– external cephalic version.
 Management of the Unsensitized
Rh-Negative Pregnant Woman
 For first-trimester pregnancy complications
and procedures :
– 50 µg of Rh D immune globulin is protective.
– Beyond 12 weeks, a full 300-µg dose is
indicated, even in the absence of detectable
hemorrhage.
– In second & third trimester: an assessment of
the volume of fetal whole blood should be
performed, and the appropriate amount of Rh D
immune globulin should be given
 Management of the Unsensitized
Rh-Negative Pregnant Woman
 Failure to administer Rh D immune
globulin when indicated may due to:
– Failure to type the patient's blood at the first
prenatal visit or to order Rh D immune globulin
when indicated
– Error in transmitting the proper blood type to
the mother's chart and to the physician
Management of the Unsensitized
Rh-Negative Pregnant Woman
– ...
– Error in typing the mother, father, or baby's
blood
– Failure to administer Rh D immune globulin
when ordered
– Unrecognized fetomaternal hemorrhage during
pregnancy
– Inadequate Rh D immune globulin for the
volume of fetomaternal hemorrhage
– Patient refusal
 Management of the Rh D-
Alloimmunized Pregnancy
 mildly affected fetuses:
– can be allowed to remain in utero until they
have achieved pulmonary maturation
 moderately to severely affected fetuses:
– may need intrauterine treatment (transfusion)
and very likely will require delivery prior to
pulmonary maturation.