HEMOLYTIC DISEASE OF THE

NEWBORN AND FETUS

Erythroblastosis fetalis
HEMOLYTIC DISEASE OF THE NEWBORN
AND FETUS:
Hemolytic disease of the new born and fetus is caused by
the destruction of the RBCs of the fetus by antibodies
produced by the mother.
Only antibodies of the immunoglobulin class G (IgG) are
actively transported across the placenta.
HDN:- it is the result of the passage of IgG antibodies
from the maternal circulation across the placenta into the
circulation of the fetus where they react with fetal red
cells lead to their destruction by the fetal
Reticuloendothelial System (RES).
 CAUSES OF (HDNF)
1) Anti D was responsible for 94% of Rh HDN, followed by Anti-c,
and anti-E, anti-e and anti-C very rare.

 the risk of immunization is only 10% of Rh-negative mother after

an Rh positive pregnancy if RhIg is not administered.

Where as the risk of immunization is 80% in Rh-negative

individuals who are transfused with 1 unit of Rh-positive RBCs

2) Immune antibodies of the ABO system become now the most
frequent

3) Occasional anti-kell (hemolysis and suppression of

erythropoiesis as Kell antigen is present on erythroid progenitors).
 HDNF

1st pregnancy= sensitization

with
Rh D + fetus
OVERVIEW OF HEMOLYTIC DISEASE OF
THE NEWBORN AND FETUS:

Three important factors must be present for HDFN to

occur:

1. the red blood cells antibody produced by the mother

must be of the IgG class.

2. the fetus must possess an antigen that is lacking in

the mother. The gene for the antigen is inherited from the
father.

3. the antigen must be well developed at birth

PATHOGENESIS:
Rh negative woman can be sensitized and form anti-D
by:-
1)Previous pregnancy with a Rh D positive fetus
2)Previous miscarriage
3)Amniocentesis or other trauma to the placenta
4)Blood transfusion
During the next pregnancy with a Rh D positive fetus,
Anti-D crosses the placenta to the fetus and coats the
fetal red cells which leads to their destruction by the RES
→ anemia and jaundice.
 PATHOGENESIS:
1. Hemolysis: the antibody-coated RBCs are removed from
the circulation in the reticuloendothelial System (RES).
2. Anemia: destruction of fetal RBCs and the resulting
anemia stimulate the fetal bone marrow to produce RBCs at
an accelerated rate which leads to immature RBCs
(erythroblast) are released into the circulation
(erythroblastosis fetalis).
3. When the bone marrow fails to produce enough RBCs,
erythropoiesis out side the bone marrow is increased in the
hemopoietic tissue of the spleen and liver
(hepatosplenomegaly).
 PATHOGENESIS:
4. sever anemia with hypoproteinemia by decreased hepatic
production of plasma proteins leads to the development cardiac
failure with generalized edema (hydrops fetalis).

Because the IgG has a half life of 25 days so sensitization and

hemolysis of RBCs continue for several days to weeks after
delivery.

5. Bilirubin:
In the fetus the indirect bilirubin (unconjugated) which produced from
the RBCs destruction and hemoglobin metabolism is transported across
the placenta and conjugated in the maternal liver to direct bilirubin.

The conjugated bilirubin is then excreted by the mother. so its do not

cause any clinical disease in the fetus.
PATHOGENESIS:
After birth: accumulation of the indirect bilirubin can
become a severe problem in the newborn infant.

The newborn liver is deficient in glucuronyl transferase

(the liver enzymes needed to conjugate indirect bilirubin).

Indirect bilirubin is released leads to jaundice and if left

untreated can cause kernicterus (permanent damage to
the brain).

Resulting in deafness, mental retardation or death.

Generally more than 18mg/dl.

intra-uterine fetal death (IUFD) from hydrops fetalis (presence
of fetal tissue edema accompanied by serous effusions in one or
more body cavities)
 DIAGNOSIS AND MANAGEMENT:
1. ABO and Rh testing

2. the Rh test should include the weak D

Weak D patient can be considered as Rh positive.

Rare weak D phenotype is caused by missing part of the Rh

antigen. Such patients may produce anti-D as an alloantibody
which cause HDN.

3. antibody detection test (antibody screening).

To detect clinically significant IgG alloantibody reactive at 37°C

in the antiglobulin phase (indirect coombs test).

Its recommended at 20-24 week of gestation.

3. Antibody specificity: if the antibody screening is positive.

 DIAGNOSIS AND MANAGEMENT:
4. paternal phenotype

5.antibody titers.

6.amnicentesis:

Patient with history of a severely affected fetus

Under ultrasound guidance, amniocentesis is done to

assess the status of the fetus. The concentration of
bilirubin can be measured.

7. cordocentesis: fetal blood is obtained and tested for

hemoglobin, hematochrit blood group type and direct
antiglobulin test
LABORATORY FINDING:

 B. mother:
 1.Rh-ve

 2.High plasma level of anti-D

MANAGEMENT AND TREATMENT:
1. intrauterine transfusion if:

A) amniotic fluid results high bilirubin.

B) cordocentesis blood sample has hemoglobin level less

than 10 g/dL.

C) fetal hydrops is noted on ultrasound examination.

2.early delivery:

when fetal lung are mature

MANAGEMENT AND TREATMENT:

Serological testing of the newborn infant:

1. ABO grouping:

ABO antigen are not fully developed in newborn so may

give weak reaction.

Infant does not have is agglutinins so reverse grouping

can not be used to confirm the forward ABO grouping.

2. Rh typing:

3. direct antiglobulin testing

 LABORATORY FINDING:
A. Baby:
 1.Anemia Hb < 12g/dL normal (14-20g/dL)
 2.High reticulocytic count

 3.Normoblast are seen in moderate and severe cases

 4.RhD +ve

 5.DAT : +ve

 6.Bilirubin increased
POSTPARTUM TREATMENT
1. Exchange transfusion:
Indication:

Obvious pallor, jaundice& sign of heart failure

Hb level <12g/dL
Positive DAT
Serum bilirubin 18-20mg/dl in a healthy baby
(>2.5Kg).
NEWBORN TRANSFUSION:
Exchange transfusions used to:

1. to remove high concentration of unconjugated

bilirubin.

2. to remove part of circulating maternal antibody.

3. to remove sensitized RBCs

4. replacement of incompatible RBCs with compatible

RBCs

5. suppression of erythropoiesis (reduce the production of

incompatible blood).
BLOOD SELECTION FOR EXCHANGE TRANSFUSION:

1. Group O (or ABO compatible) D-negative blood.

2. RBCs less than 7 days old.

3. resuspend in group AB FFP

4. CMV seronegative donors or leukocytes reduced, due to

the immunocompromised status of newborns.

5. Irradiated blood to prevent graft versus host disease.

6. Blood lack antigen corresponding to maternal antibody

7. Compatible cross-match with maternal serum.

2. Phototherapy:
After delivery phototherapy with ultraviolet light
can be used to treat hyperbilirubinaemia.
Phototherapy
 PREVENTION OF HDN:
Prevention of HDN by Rh immunoglobulin (RhIG).

RhIG is a concentrate of polyclonal anti-D IgG product

prepared and purified from pools of human plasma of D-
alloimmunized individuals.

During pregnancy and delivery mixing of fetal and

maternal blood occurs.

A significant amount of fetal RBCs can enter the maternal

circulation during pregnancy. However, the greatest risk of
immunization to Rh is at delivery.
 INDICATION:
Ante-partum administration of Rh immune globulin:
Prevent or reduces the formation of anti-D during gestation
Because of the known risk of Rh immunization during pregnancy,
unsensitized D-negative mothers should receive initial does of
RhIG.
RhIG should be given early in the third trimester at about 28
weeks of gestation.
The dose does not considered a risk to the fetus, however, a
positive direct antiglobulin test (DAT) result may be observed in
the newborn.
If the infant is Rh positive, a second dose is indicated after
delivery.
 INDICATION:
 Additional doses of RhIG during pregnancy include:
 Amniocentesis

 Cordocentesis

 Intrauterine transfusion

 Abdominal trauma.

 Abortion ectopic pregnancy

CRITERIA FOR ANTEPARTUM ADMINISTRATION
INCLUDE:

1. D-negative mothers when the fetus is D-positive or

unknown.

2. The RhIG is not indicated for the mother if the infant is
found to be D-negative.

3. A D-negative mothers who has been previously

immunized to D is not a candidate for RhIG (RhIGs is of no
benefit once a mother has been actively immunized and has
formed anti-D).

4. D- positive mothers are not candidates for RhIG.

CRITERIA FOR ANTEPARTUM ADMINISTRATION
INCLUDE:

5. mothers with weak D testing should be considered D-

positive and not received RhIG.

6.Partial RhD antigen mother can develop Rh

immunization. So they are candidates for Rh immune
globulin IgG prophylaxis

This anti-D (RhIG) dose not bind to most of the partial Rh

D erythrocytes.
 INDICATION:
 Post-partum administration of Rh immune globulin:
The Rh negative unsensitized mother should receive RhIG
soon after delivery of an positive infant.

The recommended time interval is within 72 hours after

delivery, even if the mother have been administered RhIG at
28 weeks of gestation a full post-partum dose of RhIG still
should be administered.

The mother should be D-negative

The infant should be D-positive or weak positive.

 INDICATION:
Post-partum administration of Rh immune globulin:

The partial Rh positive phenotype mothers are able to

produce anti-D.

This anti-D is indistinguishable from anti-D except that it

does not react with patient own partial D positive RBCs.

The distniction between the partial D antigen and weak D

is that the partial D-antigen differs qualitatively from
normal. While the weak D antigen differes quantitatively
from normal.
ABO HEMOLYTIC DISEASE OF THE NEWBORN:
ABO HDFN occurs most frequently in group A or B infants
to group O mothers with potent anti-A,B ( since anti-A,B is
IgG can cross placenta).
The mother history of transfusions or pregnancies unrelated
to the severity of the disease.
Therefore, ABO HDFN may occur in the fist pregnancy.
Even high tittered IgG antibodies that are transported
across the placenta incapable of causing significant RBC
destruction in an ABO incompatible fetus.
The bilirubin peak is later at 1to 3 days.
Phototherapy is sufficient for slowly rising bilirubin levels.
ABO HEMOLYTIC DISEASE OF THE NEWBORN:
Possible explanations for the mild red cell destruction
despite high levels of maternal antibody include the
following:
1. presence of A or B substances in the fetal tissues and
secretions that bind or neutralize ABO antibodies, which
reduces the number the amount of ABO antibody available
to destroy fetal red blood cells.
2. poor development of ABO antigens on fetal or infant red
blood cells.
3. Reduced number of A and B antigen sites on fetal or
infant red cells.
COMPARISON OF ABO VERSUS RH HDFN:
ABO Rh
First pregnancy. Second pregnancy.
Disease can not Disease can predicted by
predicted by titers. titers.
Antibody IgG (anti-A,B)
Antibody IgG (anti-D).
Bilirubin at birth normal
Bilirubin elevated at the
range increased after 1 to
first day.
3 days.
Anemia at birth present
Anemia at birth absent
Edema present
Edema absent
COMPARISON OF ABO VERSUS RH HDFN:
ABO Rh
Mother O blood group Mother D- negative

Baby A or B blood group Baby D- positive

Phototherapy is Phototherapy are

sufficient. required but could be

insufficient.
Exchange transfusion
Exchange transfusion
rarely required.
commonly required.
Intrauterine transfusion
Intrauterine transfusion
not required
required some times.