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Dr. Sanjay Curpad. S
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 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 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 prevention-reasonsPrimary reason - Failure to implement
prophylaxis protocols- preventable cause
Failure to administer antenatal prophylaxis
Failure to recognise clinical events causing FMH
Failure of Postnatal immunoprophylaxisSecond– spontaneous isoimmunization
(0.1-0.2%)
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 RhD-negative 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 non-anti-D red cell antibodies in pregnancy-K. Gajjar / C Spencer
Thank You