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Rh ISOIMMUNISATION
COMPETENCIES OF THE TOPIC
 Mechanism of isoimmunisation in pregnancies
 Prophylaxis
 Fetal complications
 Diagnosis
 Management
INTRODUCTION
 Landsteiner and Weiner in the year 1940, discovered Rh antigen. The individual
having the antigen is called Rh-positive and in whom it is not present, is called Rh
negative.
 INCIDENCE-
India- 5-10%
Europe and American whites- 15-17%
China -1 %
Japan- almost nil
PATHOPHYSIOLOGY
 ALLOIMMUNISATION- production of immune antibodies in an individual in response to foreign red
cell antigen derived from another individual of the same species provided the first one lacks the
antigen.
 Incidence – 6 per 1000
 METHODS OF ALLOIMMUNISATION-
1) As a result of pregnancy
2) Transfusion of mismatched blood
Factors influencing alloimmunization-
- Size of inoculum
- Coexistence of ABO incompatibility between mother and fetus
Types of antibodies-
1) IgM
2) IgG
GENETICS
 Rh factor – 49 antigens.
 Antigens located on 2 rhesus proteins- RhD and RhCE.
 Both genes located on short arm of chromosome 1.
 RhD gene- only RhD antigen
 RhCE gene- four antigens ( E, e, C, c).
 Rh positive- may be homozygous or heterozygous
 Other blood group systems- K(Kell), Fya (Duffy), Jka (Kidd), Lewis group
DIAGNOSIS
- Rh typing
- Indirect coombs test
- Antibody titre
- Gel microcolumn assay
Serious fetal anaemia is unlikely when serum levels of anti-D are <15 mIU /ml.
MANAGEMENT OF RH NEGATIVE NONIMMUNISED
WOMEN
DETECTION OF RH ALLOIMMUNIZATION
- ABO and Rh typing at first visit
- Screening for atypical antibodies- ICT
- Repeated at 28 weeks
- Paternal Rhesus typing
- 4 weekly antibody screening in non-immunized pregnancy not universally
accepted.
PREVENTION – ANTENATAL AND POSTNATAL PROPHYLAXIS
Antenatal prophylaxis-
- 1 dose regimen- at 28 weeks (300 microgram of anti-D)
- 2 dose regimen- at 28 and 34 weeks (100 and 300 microgram of anti-D)
- After anti D, titre should not be >4 at term
 National Institute for Health and Care Excellence in England recommends
fetal RhD genotyping.
 In several countries like Denmark, Sweden, the Netherlands, England, France,
Finland- fetal RhD genotype determination based on maternal cfDNA is being
routinely done.
 POST-NATAL PROPHYLAXIS
- Routine post-natal anti-D (300 microgm) – as soon as possible, preferably
within 72 hours, can be given upto 10 days and even weeks.
- Kleihauer Betke test (UK) done within 2 hrs of delivery to detect large feto-
maternal haemorrhage to calculate dose of anti-D. Better test is flow
cytometry.
- 300 microgm= 1500 IU og anti-D= neutralise 15 ml of Rh positive fetal RBCs=
30 ml of fetal blood.
MANAGEMENT OF RH NEGATIVE IMMUNISED WOMEN
- Paternal Rh phenotype and genotype- homozygous(100% affected)
- Fetal blood group (if father is heterozygous)- CVS, amniocentesis, fetal blood
sampling, maternal cfDNA(98.7 -100% )
- FIRST AFFECTED PREGNANCY-
- maternal antibody titre most useful in first affected pregnancy.
- Titre rarely exceeds critical level.
- Serial quantification of antibody titres every 4 weeks until 28 weeks and then every 2
weeks.
- SUBSEQUENT PREGNANCIES AFTER 1ST
AFFECTED-
- Predictor of severity- titre at which the at which the previous pregnancy was affected.
Assessment of fetal anaemia 10 weeks prior to the gestational age at which previous
pregnancy was affected.
ULTRASOUND ASSESSMENT-
gestational age, fetal hydrops, cardiomegaly, increased umbilical vein diameter,
hepato-splenomegaly, bowel wall. Also for invasive procedures.
MCA PEAK SYSTOLIC VELOCITY-
- superceded the invasive method of amniocentesis then spectrophotometric
analysis for estimation of bilirubin.
- Interval- 1-2 weeks
- From 18 weeks to 36 weeks
- PSV>1.5 MoM - cordocentesis
FETAL BLOOD SAMPLING AND INTRAUTERINE TRANSFUSION-
- Placental end of umbilical cord
- Needle in umbilical vein- ABO and Rh, Hb, haematocrit
- Haematocrit 30%= 8 gm/dl of Hb= indication for intrauterine
transfusion( intravenous or intraperitoneal)
- Cordocentesis- 5% fetal death if performed before 24 weeks
- Overtransfusion done so that interval between transfusion is 2-4 weeks.
- Generally 3-4 transfusions required but 10 may be required in some.
- IUT done upto 34 weeks.
- After invasive procedure no use of antibody titre.
CARE AT DELIVERY-
- Fetal surveillance reassuring- labour induced at 37-38 weeks.
- Corticosteroids given if preterm delivery anticipated.
- If delivery before 34 weeks then LSCS.
DURING DELIVERY-
- Keep cross-matched blood ready before induction of labour.
- Clamp the cord immediately
- Keep cord long for possible catheterisation
- Collect cord blood- ABO and Rh typing, bilirubin, Hb, direct coombs test
Haemolytic disease of the fetus and
newborn
 Neonates from severely affected pregnancies are less likely to show signs of
haemolytic disease
HYDROPS FETALIS
-most severe form
-Severe anaemia, tissue anoxemia, metabolic acidosis
- Hyperplasia of placental tissue
- Hypoproteinemia(liver damage)
- Congestive heart failure
- Hydrops
- Fetal death
- Sonography – Buddha position
ICTERUS GRAVIDARUM NEONATORUM-
- Baby born alive without jaundice but develops within 24 hours of birth.
- If bilirubin>20 mg/dl- kernicterus
CONGENITAL ANAEMIA OF NEWBORN
- Mildest form of the disease.
- RBCs destruction continues upto 6 weeks after which the antibodies are not
available for haemolysis.
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