6. Haemolytic Disease of the Newborn
1
Levine and stepson discovered a postpartum woman who had delivered a stillborn foetus
and an unusual case of intra-group agglutination was observed. She required post-partum
blood transfusion and as a group O patient they transfused her with whole blood from her
group O husband, she has a severe haematolytic transfusion reaction, and I was later
discovered that her serum had agglutinated with the cells of her husband. Her cells also
agglutinated with the majority of other type O donors.
She was able to be further transfused with carefully selected compatible RBCs and later
Levine and colleagues concluded that the patient had been immunised by the foetus who
carried an antigen inherited by its father. However, they did not name the antigen.
At the same time Landsteiner and wiener were performing research on blood group antigens
and they were injecting rhesus monkey RBCs into rabbits and guinea pigs so the anti-sera
they were mixing together agglutinated but not only the rhesus monkey cells but also 85% of
white research subjects in New York – it was dubbed rhesus positive, and the remainder
were called rhesus negative – that’s where the antigens name comes from.
Important antigens of the system including capital c, lower c and e were later named by a
scientist called fisher and the lower e was identified in 1945.
The other major movement in the history of HDN was screening of pregnant women being
introduced – when this took place it eventually led to a drop in cases of still births and
neonatal deaths.
.
The prophylaxis has made more women immune to it and there are fewer women that are
at risk of sensitisation.
.
Although ABO is the most frequent cause – the disease is actually quite mild, it is rhesus D or
HDN that is the most frequent cause of severe disease.
There are other causes of haemolytic disease of the new-born including anti-Kell and anti-s
as well.
First, we are going to be focussing on rhesus haemolytic disease of the new-born.
.
There are two mechanisms by which this occurs.
.
This is a mechanism which provides the baby with protection, but it can also lead to HDNB.
.
FMH – we have a rhesus negative mum and a rhesus positive father, and the baby inherits
the rhesus positive, in the first pregnancy FMH occurs which is basically blood mixing, and it
can be caused by a number or things.
Normally during labour or a traumatic delivery the rhesus blood can be transfused to the
mum – sometimes women go through ectopic pregnancies (women that have had an STI for
example or those with high blood pressure can end up having an ectopic pregnancy) which is
the pregnancy grows in the fallopian tubes.
Sometimes placental abruption – if a woman just had an abortion either spontaneous or
elective.
Sometimes in the third trimester the mother’s immune system recognises the new antigens
as non self and the mother becomes sensitised – antibodies are formed to fight the rhesus D
positive cells – in the first pregnancy the mothers immune system produces IgM antibodies
and they do not cross the placental wall so the baby is absolutely fine however in their
, 6. Haemolytic Disease of the Newborn
second pregnancy the maternal IgG antibodies are very quickly formed and they can
recognise the foetus cells as foreign and they attack the foetal cells and that causes
haemolysis – this type of HDNB is preventable.
.
1 – antibodies form the mother diffuse through the placenta and into the foetus.
2 – an attachment phase occurs, and you see the antigen on the red cell being attached to
the antibody.
3 – agglutination occurs so the RBCs and agglutinants form a bond.
4 – the macrophages produce lytic enzymes to destroy the RBCs.
5 – we then get phagocytosis – the Fc receptor of the immunoglobulin on the spleen
macrophages recognises the Fc portion of the agglutinants and this causes haemolysis.
6 – unconjugated bilirubin through macrophages gets converted to conjugated bilirubin
7 – then we get extramedullary haematopoiesis occurring as the bone marrow is
overworked and that leads to hepatosplenomegaly as that is getting rid of all the defective
RBCs.
.
Between the first and second point – because of the breakdown of RBCs we get an anaemia.
.
The liver is also enlarged – hepatosplenomegaly.
The two sever clinical presentations are hydrops fetalis and kernicterus.
There will also be raised bilirubin (as the red cells are being broken down), low haemoglobin
and an onset of anaemia.
.
One of the first clinical presentations.
Kernicterus is a rare neurological disorder that is characterised by excessive levels of
bilirubin in the blood, and we call that hyperbilirubinemia during infancy.
the bilirubin is an orange- yellow bile pigment and it is a by-product of the natural
breakdown of haemoglobin in the red blood cells (haemolysis).
Normally unconjugated bilirubin is bound to albumin and then it is converted in the liver
where it is removed – however when this doesn’t occur it accumulates in the brain causing
damage.
Toxic levels of bilirubin will accumulate and that results in a variety of symptoms and
physiological findings, so we get foetal bone marrow and hepatic tissue in the liver and an
increase in the amount of red blood cell production, we get an enlarged spleen and that
results in immature RBCs being released from the bone marrow that are unable to carry
oxygen and that leads to the anaemia.
As well as that the unconjugated, circulating bilirubin …
Symptoms and physiological findings – they appear between 2-5 days after birth, within the
first few days of life affected infants will develop abnormally high levels of bilirubin – leading
to a yellowing of skin, mucus membranes and the whites of the eyes. Toxic levels of bilirubin
accumulate when it crosses over to the brain and it can lead to life threatening
complications such as lack of energy, drowsiness, poor feeding habits, eventually it will lead
to respiratory distress and also muscle tone (hypertonia) – the foetus eventually will have
difficulty breathing.
.
The next clinical presentation is hydrops fetalis – hydrops is water and fetalis is the foetus.
1
Levine and stepson discovered a postpartum woman who had delivered a stillborn foetus
and an unusual case of intra-group agglutination was observed. She required post-partum
blood transfusion and as a group O patient they transfused her with whole blood from her
group O husband, she has a severe haematolytic transfusion reaction, and I was later
discovered that her serum had agglutinated with the cells of her husband. Her cells also
agglutinated with the majority of other type O donors.
She was able to be further transfused with carefully selected compatible RBCs and later
Levine and colleagues concluded that the patient had been immunised by the foetus who
carried an antigen inherited by its father. However, they did not name the antigen.
At the same time Landsteiner and wiener were performing research on blood group antigens
and they were injecting rhesus monkey RBCs into rabbits and guinea pigs so the anti-sera
they were mixing together agglutinated but not only the rhesus monkey cells but also 85% of
white research subjects in New York – it was dubbed rhesus positive, and the remainder
were called rhesus negative – that’s where the antigens name comes from.
Important antigens of the system including capital c, lower c and e were later named by a
scientist called fisher and the lower e was identified in 1945.
The other major movement in the history of HDN was screening of pregnant women being
introduced – when this took place it eventually led to a drop in cases of still births and
neonatal deaths.
.
The prophylaxis has made more women immune to it and there are fewer women that are
at risk of sensitisation.
.
Although ABO is the most frequent cause – the disease is actually quite mild, it is rhesus D or
HDN that is the most frequent cause of severe disease.
There are other causes of haemolytic disease of the new-born including anti-Kell and anti-s
as well.
First, we are going to be focussing on rhesus haemolytic disease of the new-born.
.
There are two mechanisms by which this occurs.
.
This is a mechanism which provides the baby with protection, but it can also lead to HDNB.
.
FMH – we have a rhesus negative mum and a rhesus positive father, and the baby inherits
the rhesus positive, in the first pregnancy FMH occurs which is basically blood mixing, and it
can be caused by a number or things.
Normally during labour or a traumatic delivery the rhesus blood can be transfused to the
mum – sometimes women go through ectopic pregnancies (women that have had an STI for
example or those with high blood pressure can end up having an ectopic pregnancy) which is
the pregnancy grows in the fallopian tubes.
Sometimes placental abruption – if a woman just had an abortion either spontaneous or
elective.
Sometimes in the third trimester the mother’s immune system recognises the new antigens
as non self and the mother becomes sensitised – antibodies are formed to fight the rhesus D
positive cells – in the first pregnancy the mothers immune system produces IgM antibodies
and they do not cross the placental wall so the baby is absolutely fine however in their
, 6. Haemolytic Disease of the Newborn
second pregnancy the maternal IgG antibodies are very quickly formed and they can
recognise the foetus cells as foreign and they attack the foetal cells and that causes
haemolysis – this type of HDNB is preventable.
.
1 – antibodies form the mother diffuse through the placenta and into the foetus.
2 – an attachment phase occurs, and you see the antigen on the red cell being attached to
the antibody.
3 – agglutination occurs so the RBCs and agglutinants form a bond.
4 – the macrophages produce lytic enzymes to destroy the RBCs.
5 – we then get phagocytosis – the Fc receptor of the immunoglobulin on the spleen
macrophages recognises the Fc portion of the agglutinants and this causes haemolysis.
6 – unconjugated bilirubin through macrophages gets converted to conjugated bilirubin
7 – then we get extramedullary haematopoiesis occurring as the bone marrow is
overworked and that leads to hepatosplenomegaly as that is getting rid of all the defective
RBCs.
.
Between the first and second point – because of the breakdown of RBCs we get an anaemia.
.
The liver is also enlarged – hepatosplenomegaly.
The two sever clinical presentations are hydrops fetalis and kernicterus.
There will also be raised bilirubin (as the red cells are being broken down), low haemoglobin
and an onset of anaemia.
.
One of the first clinical presentations.
Kernicterus is a rare neurological disorder that is characterised by excessive levels of
bilirubin in the blood, and we call that hyperbilirubinemia during infancy.
the bilirubin is an orange- yellow bile pigment and it is a by-product of the natural
breakdown of haemoglobin in the red blood cells (haemolysis).
Normally unconjugated bilirubin is bound to albumin and then it is converted in the liver
where it is removed – however when this doesn’t occur it accumulates in the brain causing
damage.
Toxic levels of bilirubin will accumulate and that results in a variety of symptoms and
physiological findings, so we get foetal bone marrow and hepatic tissue in the liver and an
increase in the amount of red blood cell production, we get an enlarged spleen and that
results in immature RBCs being released from the bone marrow that are unable to carry
oxygen and that leads to the anaemia.
As well as that the unconjugated, circulating bilirubin …
Symptoms and physiological findings – they appear between 2-5 days after birth, within the
first few days of life affected infants will develop abnormally high levels of bilirubin – leading
to a yellowing of skin, mucus membranes and the whites of the eyes. Toxic levels of bilirubin
accumulate when it crosses over to the brain and it can lead to life threatening
complications such as lack of energy, drowsiness, poor feeding habits, eventually it will lead
to respiratory distress and also muscle tone (hypertonia) – the foetus eventually will have
difficulty breathing.
.
The next clinical presentation is hydrops fetalis – hydrops is water and fetalis is the foetus.
