( Erythroblastosis fetalis )
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The most serious cause of indirect hyperbilirubinemia with anemia in newborn because
blood group incompatibility between the mother & infant which may be due to
passage of maternal Ab against fetal RBC leading to hemolysis . it include
Rh incompatibility .
ABO incompatibility .
subgroup incompatibility as Kell ( K ) , M , Duffy , C
Pathogenesis & pathophysiology :
human being is either Rh+ve who is having Rh Ag in the RBC which is either ( C, c , D
, E , e ) the most common is D Ag , or Rh-ve who is not having the Ag , when Rh –ve
expose to Rh+ve blood it start to develop Ab which is called Anti D .
So when Rh-ve mother get pregnant with Rh+ve baby & blood may go from fetus to
the mother by feto-maternal tansfusion (usually > 1ml )during pregnancy, abortion ,
or labour,so Rh Ag D pass from baby to mother lead to sensitization of the mother &
formation Anti Rh Ab initially IgM ( 19 S gammaglobulin ) which not cross the
placenta then there will be formation of IgG ( 7 S ) Ab which can cross the placenta
reaching fetal blood & causing agglutination & destruction of fetal RBC causing
haemolysis , anemia & erythroblastosis fetalis .
Haemolytic disease of Rh incompatibility usually occur in 2nd baby & Rarely occur in
1st baby because transfusion of Rh +ve fetal blood to Rh –ve mother tend to occur
near delivery that is too late for mother to become sensitized & transmit Ab to her
infant which usually need time to occur but when she is going to be pregnant with 2nd
Rh +ve baby he will get the disease .
It will occur in 1st baby when mother previously sensitized by receiving Rh +ve blood
for some reason or when she is previously abort Rh +ve baby with no treatment by
Anti D .
Once sensitization occur & development of the disease , the severity tend to be more
with successive pregnancy
When IgG Ab cross the placenta to fetal blood & causing agglutination & destruction
of fetal RBC causing haemolysis , anemia & erythroblastosis fetalis in which
anemia with compensatory hyperplasia of erythropoietic tissue leading to massive
enlargement of the liver and spleen. also, profound anemia results in pallor, signs of
cardiac decompensation (cardiomegaly, respiratory distress), circulatory collapse.
edema , ascites and massive anasarca develop in sever cases , This clinical picture of
excessive abnormal fluid in two or more fetal compartments (skin, pleura,
pericardium, placenta, peritoneum, amniotic fluid), termed hydrops fetalis that is
due to anemia , reduction in serum albumin (oncotic pressure), and heart failure .
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Incidence of Hemolytic disease of Rh incompatibility is low because : May get Rh –ve baby .
50 % of pregnancies develop feto maternal transfusion .
capacity of Rh –ve mother to form Ab is variable ( good or weak ) .
if ABO incompatibility present may partially protect against sesitization
by removal of Rh +ve cells from circulation by Anti-A or Anti-B which is
IgM that not cross the placenta
Clinicle manifestation Hemolytic disease of Rh incompatibility
It is various from mild to severe so either
develop only lab evidence of mild haemolysis ( 15 % )
or severe when the patient develop hepato-splenomegally with anaemia &
jaundice which may be present at birth or may be absent at birth & rapidly rise
within 1st 24 hr. & may lead to kernicterus , or some time appear after 1st 24
hr
In more severe cases patient may present with ( hydrops fetalis ) This clinical
picture of excessive abnormal fluid in two or more fetal compartments (skin,
pleura, pericardium, placenta, peritoneum, amniotic fluid), such patient
develop pleural effusion , pericardial effusion , oedema , massive anasarca in
addition to hepato-splenomegally , pallor , jaundice . there may be also, heart
failure , circulatory collapse , petechae , purpura .
The patient with hydrops fetalis may be present with IUD( intrauterine death )
or died shortly after birth because of respiratory distress & birth asphyxia .
Some patients may have hepatic dysfunction & hypoalbuminaemia & in
others hypoglycaemia may occur because of hyperinsulinaemia or pancreatic
islet hypertrophy .
In severe cases there may be petechae
& purpura because of
thrombocytopenia due to decrease bone marrow production or DIC .
Post Natal Dx Hemolytic disease of Rh incompatibility
In Rh –ve pregnant women with Hx of sensitization ( previous blood
transfusion ,abortion , pregnancy ) , we should suspect the case & should
aspirate cord blood or blood from infant & do
blood group & Rh,
TSB total serum bilirubin usually 3-5 mg/dL at birth but may rapidly increase
within 1st 6 hour or very high since birth or it rise in 1st day or later on .
coomb's test usually strongly +ve & may stay for few days to several month
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CBC , reticulocyte count , blood smear . usually show anaemia
increase reticulocyte count with polychromasia increase nucleated RBC,
WBC usually normal, platlet may decrease in sever cases .
when there is sign of hemolysis with -ve coomb,s test we should think of
ABO incompatibility or
non immune cause of hemolysis as:enzyme defficiency ( G6PD,PK defficiency ) .
cell membrane disease spherocytosis , elliptocytosis ,stomatocytosis )
alpha Thalassaemia .
Antinatal Dx
if we have pregnant Rh-ve women with possible sensitization by previous blood
transfusion , abortion or pregnancy .we should do parents 'blood group & Rh
then measure maternal Anti-D Ab (IgG ) of the pregnant women in 12-16 wk ,2832 wk & 36wk of gestation .
also we can do fetal blood group & Rh from fetal DNA , fetal cell from maternal
circulation by amniocentesis & PCR.
severity of fetal disease monitored by amniocentesis , percutaneous UBS (
umbilical blood sample ) & ultrasound .
Ultrasound
U/S
For Dx of IU Hydrops , early findings are organomegally ( liver , spleen , heart ) ,
double bowel sign ( bowel oedema ) & placental thickening then progress to
polyhydramnios , ascites , pleural & pericardial effusion & then skin & scalp
oedema
fetal well being (biophysical profile ) , doppler U/S for fetal distress( increase
vascular resistance ) .
Amniocentesis
It is done if there is evidence of maternal sensitisation with maternal titre of Ab
>1/16 or by U/S sign of hydrops or hemolysis, fetal distress . It is done for
measurment of increase bilirubin in the amniotic fluid by spectrophotometry done
at 18-20 week , it reflects the degree of hemolysis & risk of IUD (intrauterine death
) by the level of bilirubin . By spectrophotometric scanning of amniotic fluid wave
length demonstrate +ve optical density deviation of absorption of bilirubin from
normal at 450 nm
so there is 3 relative declining zones of OD 450 nm , 1st zone when fetus is
unaffected or mildly affected , 2nd zone the fetus moderately affected , 3rd zone
the fetus is severely affected .
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Treatment of an Unborn Infant.
If the fetus in zone 3 or if hydrops or fetal distress with anaemia & haematocrit of
25 – 30 % with pulmonary immaturity so we have to give him IU transfusion with
packed O –ve RBC done before 35 –37 week gestation ,the transfusion is either into
peritoneal cavity or more likely into umbilical vein Transfusions should achieve a
post-transfusion haematocrit of 45–55% & can be repeated every 3–5 wk .
Indications for delivery include pulmonary maturity, fetal distress, complications of
PUBS, or 35–37 wk of gestation.
Birth of live born infant
Should be attained by pediatrician when resuscitation must be ready , also fresh
low titer O-ve blood croosed matched with mother serum should be prepared
before delivery. If clinical sign of sever hemolytic anemia or hydrops ( pallor ,
HSmegally , petieche or ascites ) evident at birth &may have sever respiratory
distress or birth asphyxia so we may need to do resuscitation by endotracheal
intubation & suction ,oxygen , ambu bag with supportive measure , temperature
stabilization , correction of acidosis , then may need exchange transfusion or partial
exchange or blood transfusion (small shoot of packed RBC ) according to the state
of the infant , also patient some time may need volume expander during
resuscitation .
Prevention of Rh isoimmunization
It is done by prevent sensitization of pregnant Rh –ve woman by giving her human Anti D
globuline ( 1ml of Rh OGAM ) which combine with & eliminate RH +ve fetal RBC that
passed to maternal circulation thus prevent sensitization.
It is given at 28 - 32 week of gestation & within 72 hr. of the delivery (should be given
after each pregnancy of RH +ve baby ) .
also given within 72 hr. of abortion , delivery of ectopic pregnancy , amniocentesis ,
abdominal trauma in pregnancy , chorionic villous biopsy & trans placental hemorrhage .
also we have to prevent exposure of Rh –ve mother to Rh +ve Ag ( Rh +ve blood
transfusion
It is more common & usually result in milder haemolytic disease than Rh incomp.
The cause is reaction of maternal Anti A or Anti B Ab to A or B Ag in fetal RBC or
newborn .Usually seen in infant of type A or B blood group born to mother type O
blood group .
although Anti- A & Anti - B Ab are naturally present without previous
immunization that is usually in form of IgM that can not cross the placenta , but
when mother expose A or B Ag (during first ABO incompatibility pregnancy or
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abortion ) leading to maternal sensitization & formation of IgG
which cross
placenta & leading to fetal hemolysis during 2nd or next ABO incomp. pregnancy .
however some mother (usually type O blood group ) has naturally present Anti A
or Anti B Ab of IgG ( 7S ) type which cross the placenta easily , that is why ABO
Incompatibility can occur in the 1st pregnancy .
Although ABO Incomp. occur in 20 – 25 % of pregnancies haemolytic disease
develop in only 10 % of such of
Clinical Manifestation
Infant generally not affected at birth , most cases are mild with jaundice as the
only manifestation . Jaundice may appear in the 1st 24 hr. or later 2nd , 3rd day &
rarely develop severe jaundice & kernicterus . 10 – 20 % of patients having TSB
reaching 20 or more.
Pallor may not present ,
generally no hepatosplenomegally
hydrops fetalis extremly rare .
Diagnosis
Blood group of the mother (usually group O) & baby ( usually A or B )
Increase TSB ( often the only abnormality )
Hb. Usually normal but may be as low as 10 – 12 gm /dL .
Coomb's test either –ve or mild to moderately +ve , with increase retic. Count .
Polychromasia , nucleated RBC , microspherocyte ,
As Kell , C , e , Duffy these subgroup incomp.
Also may associated with anemia & hyperbilirubinemia
,some time Hepato-spleenomegally ,
coombs test is invariably +ve
Also some time may present with hydrops fetalis ,
exchange transfusion also may be needed some time .
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