Rh and ABO incompatibility

Introduction

Many different antigens are found on the surfaces of red blood

cells and they may cause important isoimmunization in obstetrics

Next to the ABO system, the Rh system is the second most

important blood group system.

The Rh antigens are found on red blood cell membrane protein.

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Introduction cont…

The Rh antigens are grouped in 3 pairs: Dd, Cc, and Ee.

The major antigen in this group, Rho (D), or Rh factor, is

of particular concern.

A woman who is lacking the Rh factor is said to be Rh-

negative

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Introduction

Exposure of these Rh-negative people to even small

amounts of Rh-positive cells, by either transfusion or
pregnancy, can result in the production of anti-D
alloantibody, a condition called Rh sensitization or
isoimmunization

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Introduction

If fetal red blood cells pass into the mother's circulation

in sufficient numbers, maternal antibodies to the Rh-
positive antigen may develop and cross the placenta,
causing hemolysis of fetal blood cells .

Hemolytic disease of the newborn may occur, and

severe disease may cause fetal death

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Incidence

Basque populations have the highest incidence of Rh-negativity (30–

35%).

Caucasian populations in general have a higher incidence than other

ethnic groups (15–16%).

Blacks in the United States have a rate of 8%,

African blacks 4%,

Indoeurasians 2%, and NorthAmerican Indians 1%

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Intro cont…
Definition

Rh incompatibility is the presence of different Rh types in a woman

and her partner.

In obstetrics, the significant incompatibility is when the

woman is Rh negative and the partner is Rh positive.
Rh isoimmunization (Rh sensitization)
Is production of antibody against the Rh factor by an Rh
negative woman following exposure to Rh-positive cells.
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Intro cont…
Erythroblastosis fetalis
is the condition in which large numbers of nucleated red cells
are seen in the fetal circulation,occurring in response to
excessive destruction of fetal red blood cells.

Hydrops fetalis
is generalized edema in the fetus and collection of serous fluid in
body cavities of the fetus resulting from a variety of pathologic
conditions (immune hydrops and non immune hydrops).

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Intro cont…

Hemolytic disease of the newborn

is occurrence of progressive anemia and hyperbilirubinemia in
a newborn caused by haemolysis of red blood cells, in most
cases antibody mediated

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Pathogenesis

For Rh isoimmunization to occur, the following

prerequisites must be fulfilled:

I. Rh negative mother carrying Rh positive fetus

If the father is homozygous, all of his children will be

Rh-positive; if he is heterozygous, his children will
have a 50% chance of being Rh-positive
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pathogenesis

II. Entry of the fetal Rh positive red blood cells into

maternal circulation
Fetal red blood cells are detected in maternal circulation in
6%in the first trimester, 15% in the second trimester and 30%
in the third trimester.
It may be silent or may follow obstetric complication.
Fetomaternal hemorrhage occurs in more than 50% during
delivery especially in the third stage.
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pathogenesis

Conditions that aggravate feto maternal hemorrhage are

spontaneous or induced abortion, ectopic gestation, ante partum
hemorrhage

especially abruptio placenta, amniocentesis, abdominal trauma,

and external cephalic version.

Conditions that worsen fetomaternal bleeding during labour are

manual removal of placenta, twin delivery and caesarian section

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pathogenesis

III .Development of Rh antibodies by the mother

The maternal immune system responds by producing antibodies which are

initially of IgM type (big immunoglobulin that can not pass the placental barrier).

Fetomaternal bleeding in the subsequent pregnancies results in the anamenstic

reaction producing an IgG type of antibody (small antibody that can pass the

placental barrier).

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pathogenesis

Factors that affect this maternal response are

inborn responsiveness of the mother (30% are non responders),

volume and rate of hemorrhage (as little as 0.1 ml is enough),and

presence of ABO incompatibility (reduces risk by 50 -75%).

The overall risk of isoimmunization of an Rh positive ABO

compatible fetus is 16%.

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pathogenesis

Antibodies can be detected before the delivery of the

first Rh positive fetus in 1% and in another 8% it will be

detected within 6 months of delivery and in another 8%

the level is so low that it cannot be detected until the

early part of the second pregnancy.

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pathogenesis

In addition, for hemolytic disease of the newborn and hydrops

fetalis to develop transfer of the IgG type antibody and
antibody mediated destruction of fetal red blood cells must
occur

The first neonate is usually spared but subsequent Rh positive

fetuses are affected, extent worsening with each pregnancy

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pathogenesis
Hemolytic anemia develops, the extent of which
depends on the amount of antibody.

To compensate for the ensuing anemia the fetal bone

marrow and later the extramedullary sites that produce
RBC (liver, spleen and placenta) are called to produce
red blood cells at fast rate.
This results in the appearance of young nucleated cells
in the blood stream.
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 pathogenesis
In severe cases even extramedullary hematopoiesis can
not cope with the degree of destruction.

This results in progressive anemia which eventually leads

to congestive heart failure and tissue hypoxia.
The liver parenchyma is replaced by hematopoeitic tissue.
Serum albumin falls as the result

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 pathogenesis
Portal hypertension develops from obstruction of the
portal veins.

The combination of these causes generalized edema of

the fetus called hydrops fetalis. Eventually fetal
death occurs.
Before delivery the bilirubin, mainly of unconjugated
type is cleared by the placenta.

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Pathogenesis

Following the delivery of the fetus, increasing amounts of

unconjugated bilirubin accumulate in the neonatal
circulation (because the limited capacity of the liver to
clear).

The unconjugated bilirubin crosses the blood brain barrier

and damages the basal ganglia to cause kernicterus.

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Management of unsensitized pregnancy

Prepregnancy or First Prenatal Visit

On the first prenatal visit, all pregnant women should be screened for
the ABO blood group and the Rh group, including Du.

They should also undergo antibody screening (indirect Coombs' test).

Unless the father of the baby is known to be Rh-negative, all Rh-

negative mothers should receive prophylaxis according to the
following protocol.

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Management of unsensitized pregnancy

Visit at 28 Weeks

Antibody screening is performed. If negative, 300mcg of Rh immunoglobulin (RhIgG)

is given.

If positive, the patient should be managed as Rh-sensitized.

Visit at 35 Weeks

Antibody screening is repeated. If negative, the patient is merely observed.

If screening is positive, the patient is managed as Rh-sensitized

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Management of unsensitized pregnancy

Postpartum

If the infant is Rh-positive or Du-positive, 300 mcg of RhIgG is

administered to the mother (provided maternal antibody
screening is negative).

Although RhIgG should generally be given within 72 hours after

delivery, it has been shown to be effective in preventing
isoimmunization if given up to 28 days after delivery.
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Management of unsensitized pregnancy

If the antibody screen is positive, the patient is

managed as if she will be Rh-sensitized during the next
pregnancy

Abortion

Sensitization will occur in 2% of spontaneous abortions

and 4–5% of induced abortions.

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Management of unsensitized pregnancy

In the first trimester, because of the small amount of fetal blood,

50mcg of RhIgG apparently is sufficient to prevent sensitization.

However, because the cost of RhIgG has dropped, a full 300-g

dose is usually given.

The same dose is recommended for exposure after the first

trimester.

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Management of unsensitized pregnancy

Amniocentesis, Chorionic Villus Sampling, and Cord

Blood Sampling

If the placenta is traversed by the needle, there is up to an

11% chance of sensitization.

Therefore, administration of 300 mcg of RhIgG is

recommended when these procedures are performed in the
unsensitized patient
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Management of unsensitized pregnancy

Antepartum Hemorrhage

In cases of placenta previa or abruptio placentae,

administration of 300 mcg of RhIgG is recommended.

If the pregnancy is carried more than 12 weeks from the

time of RhIgG administration, a repeat prophylactic
dose is recommended

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Management of unsensitized pregnancy

External Cephalic Version

Fetomaternal hemorrhage occurs in 2–6% of patients who undergo

external cephalic version, whether failed or successful; therefore,
these patients should receive 300 mcg of RhIgG

Delivery with Fetomaternal Hemorrhage

Fetomaternal hemorrhage so extensive that it cannot be managed

with 300 mcg of RhIgG occurs in only about 0.4% of patients.

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Management of sensitized mother
These women need specialized care with measurement of
antibody levels in titers at regular intervals, amniocentesis
for bilirubin levels, serial ultrasound for detection of hydrops
and management of neonatal anemia and
hyperbilirubinemia

Therefore, referral of these women is the correct approach

at health center level.

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 Management cont

Mildly Affected Fetus

Testing should be repeated every 2–3 weeks, and

delivery should be near term and after the fetus has
achieved pulmonary maturity

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Management cont
Moderately Affected Fetus
should be tested more frequently, every 1–2 weeks.

Delivery may be required prior to term, and the fetus is

delivered as soon as pulmonary maturity is reached.
In some cases, enhancement of pulmonary maturity by
use of corticosteroids may be necessary

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Management cont

Severely Affected Fetus

has frank evidence of hydrops (eg, ascites, pleural or

pericardial effusion, subcutaneous edema).

Intervention usually is needed to allow the fetus to

reach a gestational age at which delivery and neonatal
risks are fewer than the risks of in utero therapy.
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Management cont

If the fetus is preterm, cordocentesis or percutaneous

umbilical cord blood sampling (PUBS) is recommended
at this stage to directly assess the fetal hematocrit.

Once severe anemia is confirmed, intrauterine

transfusion can be performed directly into the umbilical
vein.

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ABO hemolytic disease

It occurs when the mother has group O blood (with anti-

A and anti-B antibodies in her serum) and fetus is group
A, B or AB.

Unlike Rh isoimmunization, 40-50% of ABO

incompatibilities occur in the first-born infant.

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ABO cont…

ABO hemolytic disease is primarily manifest following birth,

with early neonatal onset of jaundice (at < 24 hours) and

variable elevation of the indirect bilirubin level.

Management of ABO incompatibility relates to bilirubin

surveillance and phototherapy (required in 10% of cases).

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ABO cont…

The infants may have hepatosplenomegaly.

Exchange transfusion is necessary in only 1% of cases,

and the incidence of late anemia is rare.

Sequelae such as kernicterus almost never occur

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