1. Rh allo-immunisation
Dr.Sareena Gilvaz Prof & HOD of OBG JMMCH, Thrissur

2. Rhesus Blood group System
Five red cell antigens C, c, D,E and e
Rh negative is absence of D antigen

3. C, c, E & e antigens can cause erythroblastosis fetalis
Lower immunogenicity than D
No severe disease
Hence not routinely tested

4. Kell sensitization can be more severe than D
But fewer erythro. are produced  less haemolysis
Anaemia from Kell sensitization > severe than indi. by AF bilirubin
 cut off for anti kell titre is 1:8 or greater

5. ABO group system Most common cause of haemolytic dis
Anti A & anti B (IgM) cannot reach fetal erythrocyles
Resulting anaemia usually mild
Freq seen in first born infants.
Can affect future preg’s but not progressive
No erythroblastosis fetalis
Most often only phototherapy required

6. Pathophysiology in Rh - D
D immunisation  excessive & prolonged anaemia
Marked marrow erythroid hyperplasia
Extra medullary erythropoiesis  spleen & liver

7. Hydrops pathophysiology
1.Heart failure from profound anaemia
2.Hepatic dysfunction & hypoproteinaemia 
 colloid on.pr.
ascites etc
3.Tissue hypoxia  cap. Endo. leak – hydrops

8. Immune hydrops
Hb <5gm % in hydrops Ab. collection of fluid in 2 or more area of fetal body cavities Eg skin, ascites, pl.eff pericardial eff.

9. Hydropic placental changes placento megaly, can cause PE
Hydropic placental changes placento megaly, can cause PE. Pre eclampsia in mother  severe odema in mother mimicking fetal odema -mirror syndrome

10. Formerly called iso immunisation
Now called allo immunisation
Neonatal complication called haemolytic disease of newborn HDN

11. Fetal genotyping performed on :
a. Ch. villous amniocytes b. Fetal blood c. Non invasive fetal D genotype using cell free fetal DNA in mat plasma (used in UK) 85-95% accuracy cell free fetal DNA

12. Identification of allo -immunised preg
Routine practice to perform antibody screen at prenatal visit & unbound antibody in mat serum detected by indirect coombs test.

13. ICT Patient serum incubated with Rh +ve RBCs
Washed 3 times to remove non adherent proteins
Then suspend in anti-human glob. (Coomb’s serum)
Expressed as highest dilution of serum causing agg.

14. Sensibilization In sensiblized women anti D antibodies are low .
Not detected during this index preg.
Instead indentified early in a subsequent preg when rechallenged by another D positive fetus

15. Previously sensitized preg
Antibody titres high in subsequent preg
But fetus D negative - amnestic response

16. Sensitized pregnancy ICT +ve - critical value 1:16
Safe level of anti D antibody level is <15 IU /ml
Fetal / neonatal disease

17. A.F bilirubin
Measured by a spectrophotometer Change in absorbance at 450mm This diff. referred to as OD450

18. Plotted on a graph div. Into three zones of Liley

19. Liley’s graph 27- 40 wks & 3 zones
Zone I = D neg fetus or mild anemia
Zone II = lower zone 2 Hb g%
Upper zone 2 Hb 8 – 10.9g% (premature delivery or IUT)
Zone III indicates severe anemia Hb <8g%
(Fetal death likely in a wk )

20. Liley’s graph subsequently modified by Queenan
Between 14-40wks
Large indeterminate zone where bilirubin conc.does not predict fetal Hb conc.

21. In many centres PSV in MCA has replaced amninocentesis for fetal anemia
As anemic fetus preferentially shunts blood to brain to maintain adequate oxygenation

22. Diag techniques 1. Amniotic fluid bilirubin conc 2
Diag techniques 1.Amniotic fluid bilirubin conc 2.Serial USG doppler –fetal MCA –PSV 3.USG for fetal assessment 4.Fetal blood sampling

23. MCA-PSV
Accurate non invasive method for the diagnosis fetal anemia ( Mari et al 1995)
18-35wks
Before 18wks difficult & after 35wks false +ve

24. Threshold of >1.5 MOM identified for fetuses with severe anemia (sensitivity 100%)

25. If PCV >1. 5MoM ,then fetal blood sampling reqd
If PCV >1.5MoM ,then fetal blood sampling reqd. for determining need for transfusion
When haematocrit below 30% give intrauterine transfusion

26. Fetal blood transfusion
When haematocrit below 30%
2 std deviations below mean at all gest. ages

27. Indication for FBS (1-2 % fetal loss) (Cordocentesis )
Zone II & III on Liley’s curve
PSV >1.5MoM
Hydrops on USG

28. USG
USG to detect the progress of dis. from mild to severe 1.Hepatosplenomegaly 2.in portal venous diameter flow velocity (N<5mm) 3.Fluid in serous cavities ( pericardial effusion first) 4.Subcutaneous odema – later 5.Liquor disturbances –poly hydraminos 6.Placentomegaly

29. Routes of intrauterine transfusion
Intraperitoneal Intravascular Intracardiac Umb.vein Intra hepatic portion of umb.vein

30. For intraperitoneal transfusion
With early onset haemolytic disease intra peritoneal transfusion done as vascular access difficult in the cord
For intraperitoneal transfusion
Gest .age – 20 x 10 =-ml

31. Nicholaides Chart
Mean fetoplacental bl. Volume (left e.g 100ml at 27 weeks)
Multiplied by F ( right e.g 0.8 for a pre transfusion fetal hct of 10%. And a donor hct of 80%)
Accurate method to give exact amount blood can be calculated using
Mean Feto pl.bld.vol. x F = vol transfused

32. O-ve double packed RBC with haematocrit 75-85%
It should be screened
Aim is to increase fetal Hct to 50% with the IUT

33. Timing of delivery
Depends upon the severity of disease & neonatal facilities
Steroids for lung maturity
Deliver by 37-38wks (never beyond 40wks)

34. Management during labour
Cont.CTG monitoring(sinusoidal pattern late decel)
Early cord clamping
Avoid methergine
No MROP
Cord kept long
Take cord bl. for Hb, Hct, DCT, Bld Gp & Rh

35. Anti D immunoglobulin
Std dose 300g of anti D in non sensitised mother
ACOG 50 g mini dose for early preg. indication

36. Note
Anti D not required in spont.abortion less than 12wks with out surgical intervention
If in doubt give anti D
In vesicular mole now thought that trophoblast cells may express D antigen. Therefore give Anti D

37. 300 g is for 15ml fetal haematocrit
30 ml or of fetal blood

38. Kleihauer Betke test Proformed on mat.bld to assess feto mat.bleed
To mat.bld add acid solution ( citric acid PO4 buffer)
Acid will elute adult Hb – ghost cells .
Fetal cells look dark red

39. 80 fetal red cells in 50 low power field =4ml of
feto maternal hge
100 g of anti D will neutralize 4ml of feto mat. hge

40. Routine antepartum administration
Prophylactically to all D –ve women at 28 wk(300 g)
Second dose after deli if infant +ve
Without prophylaxis 1.8% woman sensitised
with prophylaxis only 0.07%
(IInd dose routine as half life of immunoglobulin is 24days
protective levels predictably persist for 6wks or so)

41. ed risk large feto mat.Hge 1. Abd trauma
2. Pl.abrutpito
3. Pl.praevia
4. Intrauterine manipulation Multifetal gest
6. MRP

42. Kernicterus Unconjugated hyper bilirubinaemia in the newborn
Unconjugated bilirubin deposition in basal ganglia & hippocampus
Profound neuronal degeneration
Surviving infants show -spasticity
muscular incoordination
M.R
Positive correlation bet bilirubin levels >18-20 mg% & kernicterus

43. Phototherapy –light increases oxidation of bilirubin
Phototherapy –light increases oxidation of bilirubin .Thus enhances renal clearance & lowers s.bilirubin

44. Other treatment modalities
Plasma pheresis
IV Immunoglobulin therapy
D positive erythrocyte mems in enteric capsules
Immunosuppression with corticosteriods
Administration of promethazine
None have proved beneficial

45. In repeated preg loss
IVF with embryo biopsy & transfer only if Rh-ve embryos
Donor insemination from Rh –ve male donor