Dr.

Samira alsagher
Elmugharif teaching hospital
Agdabia - Libya

1
 Rh Isoimmunization: it is haemolytic disease of fetus
and/or neonate due to Rh Ag-Ab reaction.
 Rh antigen was discovered on rhesus monkey
RBCs (hence the name)
 People having Rh antigen on their RBC are named
Rh+ve and people lacking it are named Rh –ve.
 RH factor is lipoprotein present as component of
RBCs cell wall.
 It is coded in 3 pairs of genes Cc,Dd,Ee – ( D- is
the most important because the D is dominant.

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 RH –ve Rh –ve
mother father
dd (homozygote)
dd

dd dd dd dd

All offspring Rh -ve

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 Rh –ve Rh +ve
father
mother
(heterozygote)
dd Dd

dd Dd dd Dd

Half offspring Rh +ve

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 Rh –ve mother Rh +vr father
dd (homozygote)
DD

Dd Dd Dd Dd

All offspring Rh + ve

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D incompatibility developed when D –ve
women is pregnant with D +ve fetus
which occure in up to 9-10 % of
pregnancy depending on the race.

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 Population incidence

chinese and japanese 1%

North american indian and inuit 1-2%

indo- eurasian 2%
african american 4-8%
Caucasian 15-16%
Basque 30-35%

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 If no preventing measures are taking
 0.7- 1.8% of these women will become
isoimmunized antenatally
 8-17% will become isoimmunized at delivery
 3-6% after spontaneous or elective abortion
 2-5% after amniocentesis
 In subsequent D +ve pregnancy of
isoimmunized women 25-30% of their offspring
have some degree of hemolytic and
hyperbilirubinemia
 20%-25% will have hydropic fetalis and often die
either in utero or in the neonatal perio

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 Pathogenesis

 Blood production in the fetus begins at about 3

weeks' and Rh antigen has been identifed in the
red cell membrane bas early as 38 days after
conception.
1- Exposure to the antigen:
Minute amount of fetal RBCs pass to the maternal
circulation with placental separation,this occure
during pregnancy and labour( the most important
risk).

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 During pregnancy due to

 Abortion
 Antipartium haemorrage
 Invasive prenatal testing :
chorion villus sampling
amniocentisis
cordocetisis
 Accidental haemorrhage

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 2- Antibody formation:
 Foetal RBCs carrying RH antigen will induce an
immunological response with formation of antibodies against
RH antigen in maternal circulation.
 1ry immune response IGM. Large and can,t cross the
placenta. this is why the first baby not affected.
 2ry immune response IgG. small and can cross the placental
barrier.
 This is why first baby affected when RH –ve mother
previously received RH +ve B.T
 Previous fetomaternal haemorrhage like ectopic / abortion

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 3- Foetal affection
 When maternal antibodies cross the placenta,they become
attached to foetal RBCS and shorten their live span.the net
result is haemolysis which lead to these clinical pictures:
1-Congenital haemolytic anaemia (mild form).
2- Icterus gravidarum neonatorum( serious form)
3- Hydrops fetalis(most severe)
 -severe intrauterine anaemia causing hyperdynamic circulation,
heart failure and subsequent generalized edema.
 Marked hematopoiesis in th liver causes hepatocellular
damage . Portal hypertension,ascites,enlargement and edema
of placental villi.
 polyhydramnios

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 Screening and management
 Any women in their 1st pregnancy should have
blood group and RH type.If she is RH –ve and
her husband are RH +ve,so the risk exists.
 To confirm maternal immunization
 Indirect coomb’s test- at 1st antenatal care visit.
 If –ve Repeat at 28 wk, then monthly
with prophylactic treatment

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 Anti D antibody injection at 28 wk and 34
wk gestation.
 Within 48-72 hour after delivery if the baby
RH +ve
 Dose : 300 mcg of RhiG intramuscular .is
enough for feto-maternal haemorrhage
equal or less than 30 ml

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 Kleihauer test
 Detection of fetal red blood cells in maternal
circulation .and quantitate size of feto - maternal
haemorrhage.
 And then the dose of RHIg given according to the
quantity of feto-maternal haemorrhage.

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 Dose of RH immune Globulin
according to indication
50 µ 300 µ g > 300 µ g

Chorionic villus Spontaneous abortion Large

sampling induced abortion transplacental
Ectopic pregnancy haemorrhage
Mismached-
Multifetal pregnancy
reductions blood
transfusion
Amniocentesis 28wks
gestations
Premature delivery
Term delivery
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 Failure of prophylaxis

1. Dose too small

2. Dose too late >72 hours

3. Patient already immunized but antibody titer too low for

laboratory recognition

4. Defective immune globulin given

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 If indirect coomb’s test + ve
 Identification of antibodies and it’s titre.
 If the albumin titre below the critical level(1:16)
or anti D concentration < or = 15 IU/ml. repeat
the titre every 2-3 weeks until the critical level is
reached.
 If the titre remain below the critica level Delivery
at 38 wk gestation.in the presence of neonatal
team.
 If the albumin titre reach the critical level or
above (1:16) proceed to confirm foetal
haemolysis and active management.

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 Active management during
pregnancy
1- U/S.SAVE ACCURATE NON INVASIVE
 When the fetus is moderatly to severly affected
signs of hydrops fetalis(Buddha attitude)
polyhydramins
cardiomegaly
Pericardial effusion
Ascitis and oedema
increse placental thickness
 Are readily detectable by u/s

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 2- Middle cerebral artery (MCA) peak
systolic velocity.
 The major advantage of MCA doppler study is
that non invasive means of detecting fetal
anemia and indecated when transfusion is
necessarly
 Sensitivity 100% for prediction of moderate to
severe fetal anaemia either in the presence or
absence of hydrops fetalis.
 False +ve 12%


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 MCA-PSV

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 3- Cordiocentesis
Indications:
 - when fetal haemolysis is expected befor 20 weeks
 -when intrauterine transfusion is decided.
Procedure:
 Percutaneous umblical blood sampling( PUBS)
 -sampling of blood from the umblical cord using
ultrasound - directed needle aspiration.
It is done to test
1- ABO and RH typing
2- haemoglobin and haematocrite values
3- bilirubin level
4- direct coomb’s test
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 4- amniocentesis
 Done after 20 wk for AF DNA RH typing and
Α F delta.O.D.450
 Aspirated AF is tested for bilirubin concentration
by spetrophotometry at wave length 450 nm.
 The optical density reading (delta.O.D.450) is
directly related to the severity of haemolysis.
 When plotted against GA on Liley’s
curve.degree of the haemolysis are obtained.

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The curve is divided into 3 prognostic zones:

Zone I (Lowest zone)

 The fetus usually unaffected
 Repeated every 4 wks
 Continue maternal antibody titre to detect rise in titre.
 Delivery at term with prophylactic treatment.

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 Zone II (MID ZONE)

 The fetus moderatelly affected

 Repeat 1-2 WKs
 Termination of the pregnancy is advised
once the L/S ratio is mature.

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 ZONE III ( highest zone)

 Fetus is severly affected

 Options include:
 Intra-uterine BT (CORDOCENTESIS)

OR
Immediate termination of the pregnancy,
and arrange for extra uterine exchange
transfusion

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 Zone III
Liley’s curve

Zone II

Zone I

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 Intra uterine transfusion
Indications:
 - Delta O D 450 within liley’s zone III.
 - to treat the fetus 10 WKs earlier than in previous
pregnancy loss or hydrops.
Character:
 Transfusion with fresh blood
 Ht% > 75%
 Cytomegalo virus –ve.
 RH –ve blood that is compatible with mother
serum.

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Site of transfusion:
- Intraperitoneal
- Umblical vein
-Fetal intrahepatic vein
When to transfuse:
 - Fetal Ht% >40% at any gestational age,no
need for transfusion.
 - Ht% < 25% at less than 26 WKs or Ht% <30%
at more than 26 WKs need transfusion.

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 Fetal Hemoglobin (g/dl) by Gestational Age
Weeks Multiples of the Median
Gestation 1.16 1.00 0.84 0.65 0.55

18 12.3 10.6 8.9 6.9 5.8

20 12.9 11.1 9.3 7.2 6.1
22 13.4 11.6 9.7 7.5 6.4
24 13.9 12.0 10.1 7.8 6.6
26 14.3 12.3 10.3 8.0 6.8
Hgb
28 14.6 12.6 10.6 8.2 6.9
30 Values 14.8 12.8 10.8 8.3 7.1
32 15.2 13.1 10.9 8.5 7.2
34 15.4 13.3 11.2 8.6 7.3
36 15.6 13.5 11.3 8.7 7.4
38 15.8 13.6 11.4 8.9 7.5
40 16.0 13.8 11.6 9.0 7.6
mild moderate severe
anemia anemia anemia 30
 Mode of delivery
 Vaginal delivery versus cls
 Management during labour
 No cord milking,cut the cord about 30 cm away from the fetus.
 Cord blood examination for
 ABO
 RH typing
 HB
 Haematocrite
 Serum bilirubin
 Direct coomb,s test.
 Exchange transfusion If HB < 100 g/l

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 Management during C/S
 Use abdominal packs in the sides of
the uterus before opening the lower
segment to prevent spilled blood from
the placenta to inter the peritoneal
cavity.
 Let the placenta to be delivered
spontaneous using control cord
traction without squeezing the uterus.


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 Other red cells antibodies
 Anti kell
 Anti c
 Anti fy and fyb
 Anti Ra and Rb

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 Anti kell
 90% of population are kell –ve
 Most kell antibodies developed because of
icompatible transfusion.
 Management of anti kell in pregnancy:
 Antibodies screen:if antikell is
present,genotype the father:if he is kell –ve …
No further investigation
 If the father is kell +ve>>> Do antibodies
titre( if the titre> 1:64 amniocentesis or
cordiocentesis is indacated.
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 ABO Incompatibility
 The mother is group O and the fetus A or B
blood group.
 Occure in 15% of all pregnancy
 Antibodies IgM, sometimes IgG.
 Its occure in 1st pregnancy with no tendency to
increase in severity with subsequent pregnancy.
 1 in 30 fetus = mild jaundice
 1 in 50 fetus = mild anemia
 1 in 3000 fetus require exchange transfusion.
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 Timeline: hemolytic disease of the newborn
HDN Amniotic fluid Maternal Fetal RhD
described bilirubin serum Maternal
measurement antibody titers Plasma
Discovery of
Rh factor
Landsteiner & Weiner Liley Curve
Queenan MCA
ΔOD450
Postnatal Modification Doppler
Exchange Noninvasive
Transfusions
ΔOD450
detection
Prevention
α-RhD Ig
60

90
50

0
0
40

0
8

36
19

19
19

19

20
19
19
 thanks
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