Dr. Sanjay Curpad. S
RED CELL ALLOIMMUNIZATION
What is it?
 A condition that has an adverse effect on the
foetal red cells in response to the maternal
immunization.
History
 1609 First recognised by French midwife
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Louise Bourgeois
20 century Icterus gravis, erythroblastosis
and hydrops as a continuum of same
pathology
1939- Levine Steton identification of ABO
blood group
1940 Lansteiner Rh group identified
1953 Chown identified pathophysiology and
foetal maternal bleeding
Rhesus antigens
Fischer and Race
 3 pairs of antigens Cc,Dd,Ee
 D is major cause of incompatibility
 1945 Indirect coombs test
 1950’s IgG & its Fc, Fab fragments
 1965- identification of Pathophysiology
 1969- Demonstration of Passive
immunization
Pathophysiology
3 stages
 Paternally derived antigen foreign to mother
derived by foetus
 Access of these red cells to maternal
circulation to mount an immune response
 Transplacental crossing of these antibodies to
initiate destruction of foetal cells
Pathophysiology cont...
 D antigen strongly immunogenic ( 50 times
more than others)
 Antibodies produced because of sensitization
in pregnancy or transfusion
 Multiple foeto-maternal bleed more likely to
produce immunization than single dose
Factors influencing immune
response
• Immunization risk if ABO compatable-16%
• Risk if ABO incompatible 1.5-2%
• Immunization depends on size of FMH
• 1ml FMH- %)% risk of immunization in ABO
compatible women
• 0.1ml FMH -31% risk
• 1% women immunised by end of 3rd trimester
• 16% risk of immunization after 1st delivery
 cDE/cde more risk of immunising
 Finally depends on immune response of
mother
 First child rarely affected in Rh
incompatibility
Incidence
• Anti D prophylaxis reduces HDN to
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1.3/100000 live births
England & Wales 17% births to Rh neg women
59% are Rh Positive foetuses
Postnatal antiD prophylaxis reduced
frequency to 1 in 21000 births
500 foetus develop HDN with loss of 20
foetus before 28 weeks, 20-25 babies and 45
foetus affected
Prevention
 Administration of anti D immunoglobulin
dramatically reduces rate of
alloimmunization
 Administration within 72 hours of sensitising
event reduces risk of immunization by 90%
 All Rh neg women delivering Rh pos babies to
undergo screen for quantity of FMH to
determine additional dose required(British
committee for standards in Haematology)
Prevention cont...
Antenatal prophylaxis
NICE - recommendations
 AntiD 500 IU @28 & 34 weeks
 1500 IU @ 28 weeks
Failure of preventionreasons
Primary reason - Failure to implement
prophylaxis protocols- preventable cause
 Failure to administer antenatal prophylaxis
 Failure to recognise clinical events causing
FMH
 Failure of Postnatal immunoprophylaxis
Second– spontaneous isoimmunization (0.10.2%)
Preparations
 Pooled sera- Risk of Infection ( west Nile
fever, Creutzfeldt-Jokob disease etc)
 Recombinant technology
Non Rh D alloimmunization
 Antenatal screen detects clinically significant
antibodies in 0.24-1% patients
 Incidence of RhD isoimmunization decreasing
hence more importance to other causes
 43 other redcell antigens implicated
 Other important causes antic, anti Kell, less
so in anti E, anti C, anti k & anti Fya
Non Rh D alloimmunization
 Manitoba study anti c resulted in 2-7 fold
greater incidence of non Anti RhD
haemolytic disease
 Study from Netherlands- 10% of cases
involved anti K, 3.5% anti-c.
Anti Kell antibody
• 20 antigens
• Kell (K) & Cellano(k) are strongest
immunogens
• 91% population Kell negative(kk)
• Development of immunization
Previous transfusion (most common)
Previous pregnancy (less common)
Naturally ( rare)
Kell antibodies Cont...
 Partners are likely to be Kell positive in 10%
 Potential incompatibility in 5% ( because of
heterozygosity)
 2.5-10% of Kell immunised pregnancies
deliver affected infants, half of them require
intervention
Kell antibodies Cont...
 Causes suppression of erythropoisis rather
than red cell destruction
 Not affected by previous obstetric history
 Maternal Kell antibody titres – No co relation
to severity
Management –Diagnosis if not
previously affected
 Obstetric history
 Paternal Blood group
 Prenatal diagnosis of Foetal Rh D status- 1997
Lo et.al
 Maternal Serology Indirect IAT ( Coombs test)
• Non-invasive fetal genotyping using maternal
blood is now possible for D, C, c, E, e and K
antigens performed in the first instance for
the relevant antigen when maternal red cell
antibodies are present.
• For other antigens, invasive testing (chorionic
villus sampling [CVS] or amniocentesis) may
be considered if fetal anaemia is a concern or
if invasive testing is performed for another
reason (e.g. karyotyping).
Referral to a fetal medicine specialist
 when there are rising antibody levels/titres
 level/titre above a specific threshold or
ultrasound features suggestive of fetal
anaemia
Previously affected baby
 Maternal serum testing for titres
 Percutaneous Umbilical blood sampling
(PUBS)- Cordocentesis
 Real-time Ultrasonography Peak MCA
 Amniotic fluid spectrometry no longer used
Management anti Kell
 Anti Kell titres – no co relation with severity
 MCA dopplers helpful in detection of foetal
anaemia
Referral to foetal medicine
clinic
 For antibodies other than anti-D, anti-c and
anti-K
 A history of previous significant HDFN
 Intrauterine transfusion (IUT)
 A titre of 32 or above, especially if the titre is
rising as rising titres correlate with increasing
risk and severity of anaemia.
MCA DOPPLERS
MCA – psv dopplers
 Reference range for normal foetuses 0.86 to
1.16 times median
 Moderate to severe anaemia if ≥ 1.5 times of
median
Management
 Titers ≤ 1:64 testing for titres every 4 weeks
prior to 28 weeks and 2 weeks after 28 weeks
 Titres > 1:64 referral to tertiary centre
 Previous h/o Hydrops see at 14-16 weeks
review
 MCA dopplers start 18 week/ atleast
fornightly
 Stable MCA below 1.29 MoM is reassuring. If
antibodies are high, but stable and MCA
persistently normal, foetal genotyping should
be considered- Negative result will avoid
further
 When MCA peak systolic velocity reaches 1.5
MoM before 32 weeks - foetal blood sampling
to detect foetal haemoglobin
 Delivery- high risk affected pregnancies 36-38
weeks
 Low risk no evidence - ?38-40 weeks.
Management of mother
• For antibodies other than anti-D, anti-c, anti-C,
anti-E or anti-K, maternity staff should liaise with
their local transfusion laboratory to assess and
plan for any possible transfusion requirements,
as obtaining the relevant blood may take longer
• Pregnant women with red cell antibodies, who
are assessed as being at high risk of requiring a
blood transfusion, should have a cross-match
sample taken at least every week.
Management of Mother
• Anti-D immunoglobulin should be given to RhDnegative women with non-anti-D antibodies for
routine
• Antenatal prophylaxis, for potential antenatal
sensitising events and postnatal prophylaxis.
• If immune anti-D is detected, prophylaxis is no
longer necessary.
• Discussion and liaison with the transfusion
laboratory are essential in determining whether
anti-D antibodies are immune or passive in
women who have previously received anti-D
prophylaxis.
References
 RCOG green top giuideline
 Red cell immunization review Bidyut Kumar
et-al
 Review Diagnosis and management of nonanti-D red cell antibodies in pregnancy-K.
Gajjar / C Spencer
Thank You