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Rh Incompatibility
Patraporn Kinorn
Background
The Rh factor (ie, rhesus factor) is an
red blood cell surface antigen that
was named after the monkeys in
which it was first discovered.
Rh incompatibility, also known as Rh
disease, is a condition that occurs
when a woman with Rh-negative
blood type is exposed to Rh-positive
blood cells, leading to the
development of Rh antibodies
Rh incompatibility can occur by two main
mechanisms.
The most common type occurs when an
Rh-negative pregnant mother is exposed
to Rh-positive fetal red blood cells
secondary to fetomaternal hemorrhage
during the course of pregnancy from
spontaneous or induced abortion,
trauma, invasive obstetric procedures, or
delivery.
Rh incompatibility can also occur
when an Rh-negative female receives
a blood transfusion that contains Rh
antigens. In part, this is the reason
that blood banks prefer using blood
type "O-negative" or "type-O, Rh
negative," as the universal donor
type, especially in females
The most common cause of Rh
incompatibility is exposure to an Rhnegative mother by Rh-positive fetal
blood during pregnancy or delivery,
whereby red blood cells from the fetal
circulation leak into the maternal
circulation. After a significant
exposure, sensitization occurs and
maternal antibodies are produced
against the foreign Rh antigen.
Once produced, maternal Rh
immunoglobulin G (IgG) antibodies may
cross freely from the placenta to the fetal
circulation, where they form antigenantibody complexes with Rh-positive fetal
erythrocytes and eventually are destroyed,
resulting in a fetal alloimmune-induced
hemolytic anemia. Although the Rh blood
group systems consist of several antigens
(eg, D, C, c, E, e), the D antigen is the
most immunogenic; therefore, it most
commonly is involved in Rh incompatibility.
Pathophysiology
The amount of fetal blood necessary to
produce Rh incompatibility varies. In one
study, less than 1 mL of Rh-positive blood
has been shown to sensitize volunteers
with Rh-negative blood. Conversely, other
studies have suggested that 30% of
persons with Rh-negative blood never
develop Rh incompatibility, even when
challenged with large volumes of Rhpositive blood.
Therefore, most firstborn infants with Rhpositive blood type are not affected
because the short period from first
exposure of Rh-positive fetal erythrocytes
to the birth of the infant is insufficient to
produce a significant maternal IgG
antibody response.
The risk and severity of sensitization
response increases with each
subsequent pregnancy involving a
fetus with Rh-positive blood.
In women who are prone to Rh
incompatibility, the second pregnancy
with an Rh-positive fetus often
produces a mildly anemic infant,
whereas succeeding pregnancies
produce more seriously affected
infants who ultimately may die in
utero from massive antibody-induced
hemolytic anemia
Risk of sensitization depends
largely upon the following 3 factors:
Volume of transplacental hemorrhage
Extent of the maternal immune
response
Concurrent presence of ABO
incompatibility
Race
Approximately 15-20% of whites, as
opposed to 5-10% of African
Americans, have the Rh-negative
blood type.
Among individuals of Chinese and
American Indian descent, the
incidence of Rh-negative blood type is
less than 5%.
History
History of prior blood transfusion
Rh blood type of the mother
Rh blood type of the father (55% of
Rh-positive men are genetically
heterozygous for the Rh antigen and,
therefore, produce Rh-negative
offspring when mating with Rhnegative women 50% of the time.)
Previous pregnancies, including
spontaneous and elective abortions
Previous administration of Rh IgG
Mechanism of injury in cases of trauma
Presence of vaginal bleeding and/or
amniotic discharge
Previous invasive obstetrical procedures,
such as amniocentesis, cordocentesis,
amnionic villous sampling, or ectopic
pregnancy
It is important to note that a large
fetal-maternal hemorrhage may occur
without symptoms and with little or no
evidence of trauma. Therefore, a high
index of suspicion is warranted, and a
low threshold for treatment is
indicated
Physical
Evaluation of the vital signs and primary
survey of the airway and cardiovascular
system are indicated to ensure maternal
stability.
A thorough pelvic examination is required.
In situations in which abdominal and/or
pelvic trauma is a consideration, inspect for
evidence of bruising that may suggest the
possibility of significant fetomaternal
hemorrhage.
When an infant with an Rh-negative
mother is delivered in the ED, a
thorough physical examination of the
infant must be performed after initial
stabilization, and a neonatologist
must be consulted immediately.
Physical findings may vary from mild
jaundice to extreme pallor and
anemia with hydrops fetalis.
Causes
Factors that influence whether or not an Rhnegative pregnant female can develop Rh
incompatibility include the following:
Ectopic pregnancy
Placenta previa
Placental abruption
Abdominal/pelvic trauma
In utero fetal death
Any invasive obstetrical procedure (eg,
amniocentesis)
Lack of prenatal care
Spontaneous abortion
Other Problems to be Considered
ABO incompatibility
Autoimmune hemolytic anemia
Microangiopathic hemolytic anemia
Spherocytosis
Hereditary enzyme deficiencies
Alpha thalassemia
Chronic fetomaternal hemorrhage
Twin-twin transfusion
Erythroblastosis fetalis
Hydrops fetalis
Lab Studies
Prenatal emergency
care
Determination of Rh
blood type is required
in every pregnant
female.
In a pregnant woman with Rh-negative blood
type, the Rosette screening test often is the first
test performed. The Rosette test can detect
alloimmunization caused by fetomaternal
hemorrhages of as little as 4-7 of RBCs. When
a high clinical suspicion of large fetomaternal
hemorrhage is present (>30 mL RBCs), the
Kleihauer-Betke acid elution test often is
performed. The Kleihauer-Betke test is a
quantitative measurement of fetal red blood
cells in maternal blood, and it can be valuable
for determining if additional amounts of Rh IgG
should be administered. The amount of Rh IgG
required for treatment is at least 20 mcg/mL of
fetal RBCs.
Obtaining maternal Rh antibody titers
can be helpful for future follow-up care
of pregnant females who are known to
be Rh-negative and may be initiated
from the ED.
High levels of maternal Rh antibodies
suggest that Rh sensitization has
occurred, and further studies, such as
amniocentesis and/or cordocentesis, may
be necessary to evaluate the health of the
fetus.
Postnatal emergency care
Immediately after the birth of any infant
with an Rh-negative mother in the ED or
prehospital setting, examine blood from
the umbilical cord of the infant for ABO
blood group and Rh type, measure
hematocrit and hemoglobin levels,
perform a serum bilirubin analysis,
obtain a blood smear, and perform a
direct Coombs test.
A positive direct Coombs test result confirms
the diagnosis of antibody-induced hemolytic
anemia, which suggests the presence of Rh
incompatibility.
Elevated serum bilirubin measurements, low
hematocrit, and elevated reticulocyte count
from the neonate can help determine if an early
exchange transfusion is necessary.
An emergent exchange transfusion by a
neonatologist specializing in this procedure is
required in infants born with erythroblastosis
fetalis, hydrops fetalis, or kernicterus
Imaging Studies:
In the ED, ultrasound imaging studies
of a pregnant female with suspected
Rh incompatibility is limited to the
pelvic ultrasound.
Fetal ascites and soft tissue edema are
definite signs of severe involvement.
Once hydrops fetalis has developed, the
sonographic evidence includes scalp
edema, cardiomegaly, hepatomegaly,
pleural effusion, and ascites
Other Tests
Perform fetal monitoring in cases of
suspected fetal distress. Abnormal
fetal heart tones and ultrasound
evidence of fetal or placental injury
are indications of worsening fetal
condition requiring emergent delivery,
ideally in a center specializing in highrisk obstetrical care.
Prehospital Care
When possible, prehospital care
personnel should direct their efforts
on stabilization of the mother and
infant, followed by immediate
transport to a facility specializing in
high-risk obstetrical and neonatal
care.
Emergency Department Care:
ED care of the pregnant woman with Rh-negative blood and
a suspected fetomaternal hemorrhage varies depending on
the presentation of the patient and the gestational age of the
fetus.
When an infant with Rh incompatibility is delivered in the ED,
a more aggressive approach is required, centering on
respiratory and hemodynamic stabilization of the infant and
determining the need for an emergent exchange transfusion
and phototherapy by a neonatologist.
Obtain the Rh status of the pregnant
female.
If the mother has Rh-negative blood and
has not been sensitized previously,
administer human anti-D immune
globulin (Rh IgG) and refer the woman to
an obstetrician for further evaluation.
If the mother has been sensitized
previously, as determined by elevated
maternal Rh antibodies, administration
of Rh IgG is of no value. In this situation,
prompt referral to a center specializing in
high-risk obstetrics is warranted.
Rh IgG, first released for general use in 1968, has
been remarkably successful in the prevention of
Rh incompatibility. In the Rh-negative mother, the
preparation is administered after a suspected
fetomaternal hemorrhage. The exact mechanism
by which passive administration of Rh IgG
prevents Rh immunization is unknown. The most
likely hypothesis is that the Rh immune globulin
coats fetal RBCs containing Rh antigens on their
surface. These exogenous antibody-antigen
complexes cross the placenta before they can
stimulate the maternal endogenous immune
system B cells to produce IgG antibodies
Since Rh IgG became the standard of
care in the US, the risk of Rh
incompatibility has been reduced from
10-20% to less than 1%. Because of
its short half-life, Rh IgG routinely is
administered once at 28-32 weeks
gestation and again within 72 hours
after birth to all Rh-negative pregnant
females as a part of routine prenatal
care.
The current recommendation is that every Rhnegative nonimmunized woman who presents to
the ED with antepartum bleeding or potential
fetomaternal hemorrhage should receive 300 mcg
of Rh IgG IM. For every 30 mL of fetal whole blood
exposed to maternal circulation, 300 mcg of Rh
IgG should be administered. A lower 50-mcg dose
preparation of Rh IgG is available and
recommended for Rh-negative females who have
termination of pregnancy in the first trimester when
fetomaternal hemorrhage is believed to be minimal
ตาราง
Further Inpatient Care:
After administering Rh IgG in the ED,
promptly refer the Rh-negative
pregnant mother of an Rh-positive
fetus to an obstetrician at an
institution equipped for high-risk
obstetrical care.
Deterrence/Prevention
Stress the importance of early
prenatal care to each pregnant female
presenting to the ED. Early
administration of Rh IgG in
conjunction with early prenatal care is
the best means to prevent Rh
incompatibility
Complications:
Emergent delivery of an infant born
with hydrops fetalis should be as
nontraumatic as possible. Ideally, a
neonatologist who is prepared to
perform an exchange transfusion
should attend to the infant
immediately.