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HAEMOLYTIC DISEASE OF THE NEW BORN (HDN)
 Haemolytic disease of the newborn (HDN) occurs when the mother
has anti-red-cell IgG antibodies in her plasma that cross the placenta
and bind to fetal red cells bearing the corresponding antigen.
 The three most common red cell alloantibodies which cause
significant HDN are anti D, anti c and anti Kell (anti K).
 Fetal red cells binding sufficient maternally derived antibody are
destroyed in the fetal reticuloendothelial system, producing
extravascular haemolysis and a variable degree of fetal anaemia.
 In severe cases the fetus may die in utero of heart failure (hydrops
fetalis). If the fetus survives birth, the neonate rapidly develops
jaundice and is at risk of neurological damage due to the high
Bilirubin level.
RH - HDN
Pathogenesis:
1. A Rh (D) negative mother has pregnancy with a Rh (D)
positive baby
2. During delivery Rh-positive red blood cells cross the
placenta into the mother circulation and sensitize the
mother to form anti-Rh sensitization is more likely if
the mother and baby are ABO compatible.
3. Anti-D cross the placenta to the foetus (baby) during
the next pregnancy with Rh (D) positive baby, coat the
foetal red cells with antibody and results in R.E System
destruction of these cells
Clinical features
1. Severe disease : intrauterine death
2. Moderate disease : the baby born with severe anaemia
and jaundise
3. Mild disease : mild anaemia
Laboratory findings at
birth
1. Cord blood
* variable anaemia (haemoglobin<16 g/dl)
 High reticulocyte count
 Baby Rh (D) positive
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 Direct coombs test positive
 Increased serum bilirubin
 Presence of erythroblast in blood film
2. Mother : is Rh (D) negative with high plasma level antiRh (D)
Treatment
Exchange transfusion
Management
of
pregnant
women and prevention
1. The ABO and Rh blood groups of all pregnant mother
determined early in pregnancy
2. The severity of the haemolytic disease can be assessed
by estimation the bile pigment derivatives in the
aminotic fluid
3. Suitable fresh blood should be available at the time of
induction for exchange transfusion
4. A birth the babies of Rh-negative who do not have
antibodies must have their Cord blood grouped for
ABO and Rh :
- If the baby Rh-negative ( no need for
treatment )
- If the baby Rh-positive (prophylactic
anti-D should be administered)
5. Prevention of Rh immunization : by giving (anti-D) to
an Rh (D) negative mother giving birth Rh-positive
baby . The routine dose is 500 i.u of anti-D giving
intramuscular within 72 hours of delivery.
ABO haemolytic disease of the new born
 Hemolytic disease due to anti-A or anti-B is almost
confined to group A and B infants born to group O
mother , since it is mainly group O mother who have
anti-A and anti-B of the IgG class
 ABO hemolytic disease may found in the first
pregnancy and may not affect subsequent pregnancies
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 Child rarely requires treatment by exchange
transfusion
 Blood film shows auto agglutination and shperocytosis
Development of red cell antibodies in the mother may occur
either as a result of:
1. Previous pregnancies (because fetal blood displaying paternal red
cell antigens frequently enters the mother’s circulation during
pregnancy).
2. As a result of a previous blood transfusion.
The three most common red cell alloantibodies which cause
significant HDN:
1- Antibody to the Rh antigen:
- The most common is anti D.
- This develops in RhD negative women who have carried a
RhD positive fetus.
- It rarely affects the first pregnancy although it can sensitize
the mother so that subsequent pregnancies with RhD positive
babies boost antibody production progressively, putting later
pregnancies at increasing risk.
- Smaller family sizes and the introduction of prophylaxis with
RhD immunoglobulin have reduced the incidence and
severity of this condition.
- The fetus is only at risk if its red blood cells express the
antigens against which the antibody is directed (e.g. if a RhD
negative woman with anti D is carrying a RhD positive fetus,
there is a risk that the fetus will be affected, but if the fetus is
RhD negative the baby will not be at risk of HDN).
- The next most common causes of severe HDN are the rhesus
antibody anti c.
2- Kell antibody (anti K).
- In HDN due to anti K, the antibody also causes reduced fetal
red cell production.
- This is due to anti K binding to red cell progenitor cells; in
such cases the anaemia is often very severe while jaundice
may be minimal. Although it is not usually severe.
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3- Antibodies of the ABO blood group system
- in a group O mother with naturally occurring anti-A and
anti-B of the IgG subclass which can cross the placenta.
- HDN due to ABO incompatibility occurs when a group O
mother with IgG anti-A or IgG anti-B is carrying a fetus of
blood group A or blood group B respectively.
- The most common presentation of ABO HDN is jaundice
(un-conjugated hyperbilirubinaemia).
- The direct antiglobulin test is usually (but not always)
positive.
- Severe anaemia in HDN due to maternal anti-A or anti-B is
uncommon in Caucasians in the UK, but is commoner in
some other ethnic groups, especially among women of
African or Caribbean origin.
Prevention of HDN due to anti RhD
Anti RhD immunoglobulin (anti D)
- Anti-D immunoglobulin (Routine antenatal anti-D prophylaxis) is
prepared from plasma of donors who have high levels of plasma
anti-D due to exposure to RhD positive cells following pregnancy
or intentional immunization.
- Anti-D products contain specified levels of anti D and are available
for intramuscular or intravenous administration.
- Anti D is administered to RhD negative women who may have
been exposed to RhD positive fetal red cells that have entered the
maternal circulation.
- The anti D destroys the RhD positive red cells and prevents active
immunization, thus preventing the production of RhD antibodies.
Potentially sensitizing events during pregnancy
- Potentially sensitizing events (PSEs) are events that may cause
feto-maternal bleeding and can cause the mother to develop anti
D.
- If the pregnancy has reached 20 weeks or longer, patients with
any of these events should receive anti D followed by a test that
determines the volume of fetal red cells in the maternal
circulation (a Kleihauer test or equivalent), as it may be necessary
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to give a bigger dose of anti D if more than 4 ml of fetal cells
entered the mother’s circulation.
- If there is repeated antepartum haemorrhage (APH) during the
pregnancy, further doses of anti D should be given at six-weekly
intervals.
Fetal Haemoglobin (The Kleihauer test).
Principle:
- The identification of cells containing haemoglobin F depends on the
fact that they resist acid elution to a greater extent than do normal
cells; thus, in the technique described in the following, they appear as
isolated, darkly stained cells among a background of palely staining
ghost cells. The occasional cells that stain to an intermediate degree
are less easy to evaluate; some may be reticulocytes because these
also resist acid elution to some extent.
Reagents Fixative. 80% ethanol.
Elution solution:
Solution A: 7.5 g/l haematoxylin in 90% ethanol.
Solution B: FeCl3, 24 g; 2.5 mol/l HCl, 20 ml; doubly distilled water to 1
litre.
For use, mix well 5 volumes of A and 1 volume of B. The pH is
approximately 1.5. The solution can be used for about 4 weeks; if a
precipitate forms, the solution should be filtered.
Counterstain. 1 g/l aqueous erythrosin or 2.5 g/l aqueous eosin.
Method
1. Prepare fresh air-dried films.
2. Immediately after drying, fix the films for 5 min in 80% ethanol in a
Coupling jar.
3. Then rinse the slides rapidly in water and stand them vertically on
blotting paper for about 10 min to dry.
4. Next, place the slides for 20 sec in a Coupling jar containing the
elution solution.
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5.
6.
7.
8.
Then wash the slides thoroughly in water.
Finally place them in the counterstain for 2 min.
Rinse in tap water and allow them to dry in the air.
Result: Fetal cells stain red and adult ghost cells stain pale pink.
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