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