Rhesus Isoimmunisation Dr Adegoke.pptx

1. RHESUS ISOIMMUNISATION

2. OUTLINE
• INTRODUCTION

3. INTRODUCTION
• The Rh factor (Rhesus factor) is a red blood cell surface antigen that was
named after the monkeys in which it was first discovered.
• Rh incompatibility, also known as Rh disease, is a condition that occurs
when a woman with Rh-negative blood type is exposed to Rh-positive
blood cells, leading to the development of Rh antibodies.
• There are two main mechanisms by which Rh incompatibility can occur:
1. The most common type occurs when a Rhesus negative pregnant mother
is exposed to Rh-positive fetal red blood cells secondary to fetomaternal
hemorrhage during the course of pregnancy from spontaneous or
induced abortion, trauma, invasive obstetric procedures, or normal
delivery.

4. INTRODUCTION(cont’d)
2. Rh incompatibility can also occur when a Rh-negative female
receives a Rh-positive blood transfusion
• The most common cause of Rh incompatibility is exposure from a Rh-
negative mother by Rh-positive fetal blood during pregnancy or
delivery.
• As a consequence, blood from the fetal circulation may leak into the
maternal circulation, and, after a significant exposure, sensitization
occurs leading to maternal antibody production against the foreign Rh
antigen.

5. INTRODUCTION(cont’d)
• Once produced, maternal Rh immunoglobulin G (IgG) antibodies
persist for life and may cross freely from the placenta to the fetal
circulation, where they form antigen-antibody complexes with Rh-
positive fetal erythrocytes and eventually are destroyed, resulting in a
fetal alloimmune-induced hemolytic anemia.
• Although the Rh blood group systems consist of many antigen
subtypes (eg, D, C, c, E, e), the D antigen is the most immunogenic;
therefore, it most commonly is involved in Rh incompatibility.

6. RHESUS SYSTEM
• Rhesus genes = chromosome 1. (short arm)
• Rh genes C, D, and E (dominant genes)
• c, d, and e genes (recessive genes).
• Each chromosome has a C locus, a D locus, and an E locus
• Rhesus D antigen (or Rhesus factor) is the most important or antigenic of all the
Rh antigens.
• Absence = rhesus negative.
• Rhesus system is inherited by Mendelian model of Inheritance. The genotype can
be as follows:
• CDe/cDE Homozygous Rh (D) positive
• CDe/cde Heterozygous Rh (D) positive
• Cde/cde Rhesus negative

7. • Heterozygous Rh (D) positive - 55%
• Homozygous Rh (D) positive - 45%
N.B: Rhesus c and E antigens can also cause maternal
sensitization.

8. EPIDEMIOLOGY
• The incidence of rhesus negativity varies.
• Basque of Spain 30-35%,
• Caucasians 15-16%,
• American Blacks 8%,
• African Blacks 4%, and
• Mongoloid nil

9. AETIOLOGY OF RHESUS ISOIMMUNISATION
• Rhesus disease = Rh –ve woman is sensitized = antibodies cross the
placenta to affect the fetus.
• The sensitization of the Rh –ve woman:
• Transfusion of incompatible blood
• Feto-maternal haemorrhage
• Sensitizing conditions include:
• Silent feto-maternal haemorrhage = 1-2%
• Vaginal delivery
• Abortions: - spontaneous (3-4% risk)
- induced abortions (5-25% risk)

10. AETIOLOGY(Cont’d)
• Antepartum haemorrhage – placenta praevia and placental abruption
• Manual removal of the placenta
• Caesarean section
• External version
• Invasive prenatal testing – chorion villus sampling, amniocentesis and
cordocentesis

11. PATHOGENESIS
• Development of antibodies depends on some factors:
1. Inborn ability to respond to Rh antigenic stimulus = 2/3 of the Rh –
ve women are responsive.
2. ABO incompatibility is protective = reduces the incidence from
about 16% to about 1.5-2%.
3. Variation in the strength of the Rh antigenic stimulus = CDe/cde
genotype seems to be relatively ‘strong’.
4. Volume of fetal blood entering the maternal circulation.
Critical sensitising volume is 0.25ml although sensitization can occur with as
little as 0.1ml

12. • 5. When conditions are favourable for the formation of antibodies:
• IgM (Saline Ab), (abt 7 days after stimulation).
• IgG (Albumin antibody), 7S immunoglobulin, 21 days after stimulation = IgG
crosses the placenta

13. EFFECTS ON THE FETUS
• Haemolysis – the coated fetal RBCs = reticulo-endothelial cells
• anaemia and release of increased amount of unconjugated bilirubin
• increased extramedullary erythropoiesis with immature erythroblasts in the
fetal circulation
• unconjugated bilirubin passes through the placenta into the maternal blood
• Severe anaemia: it occurs when destruction of fetal RBCs far exceeds
production
• Placental hyperplasia 2o to hypoxia

14. EFFECTS ON THE FETUS(Cont’d)
• Erythroblastosis fetalis characterised by:
• Extramedullary haematopoiesis
• Cardiac failure
• Generalized edema
• Ascites
• Pericardial/pleural effusion
• Placental edema

15. EFFECTS ON THE NEONATE
• Severe anaemia = HF, ascites, edema etc
• Hyperbilirubinaemia = immature liver (low level of
glucuronyltransferase)

16. MANAGEMENT OF UNSENSITISED RHESUS
NEGATIVE PREGNANCY
• First visit = Rhesus status and screening test for immune antibodies
(ICT). If Rhesus negative,
• Test paternal Rhesus status. If Rh –ve, no risk of Rh +ve fetus or Rh
disease. If Rh +ve,
• Monitor atypical antibody level at
• 24 weeks
• 28 weeks. If negative, give RhIgG
• 35 or 36 weeks

17. • Postpartum, take fetal cord for Rhesus status, PCV, DCT and bilirubin
level. If rhesus +ve,
• Give standard dose of anti-D IgG (RhIgG) within 72 hrs of delivery
(give up to 28 days, if necessary).
• Kleihauer-Betke test (acid elution test) on maternal blood = estimate
volume of fetal blood = fetal RBCs in x50 LPF (80 fetal RBCs = 4mLof
fetal blood, 0.05ml = 1 cell).
• 1500 IU(300μg) of RhIgG(RhoGAM) neutralizes 15mL of Rh +ve blood
• Anti-D IgG prophylaxis reduces risk of isoimmunisation to 0.2%

18. ]FG00PPPP
• Give RhIgG in case of some fetomaternal risk states:
• Abortion: 1st trimester = 50μg (250 IU)
2nd trimester = 300μg
• Amniocentesis, CVS, Cordocentesis = 300 μg
• APH – placenta praevia, placental abruption = 300 μg stat, repeat if pregnancy
is carried more than 12 weeks after the administration of the anti-D IgG
• ECV = 300 μg RhIgG. It carries 2-6% risk of fetomaternal haemorrhage.
• Avoid manual removal of placenta as much as possible during CS in a
Rh –ve woman.
• Pack off the uterus from peritoneal cavity
• Amniocentesis = under direct ultrasound guidance

19. • COOMB’s TEST – an antiglobulin test.
• Coomb’s reagent is an immune anti-globulin .
• DCT (DAGT) = detects an affected fetus at birth
• Cells from fetal cord + reagent = agglutination if affected.
• ICT (IAGT) = detects and measures antibody in the maternal serum.
• Maternal serum + test cells = coated cells + reagent = agglutination if
sensitized.
• Dilute maternal serum to quantify antibody (titre)

20. MANAGEMENT OF PREGNANCY
COMPLICATED BY RHESUS IMMUNISATION
• Depends on two factors:
• Whether the patient has a history of an affected fetus in a previous
pregnancy.
• Maternal antibody titre
• a) No history of previous fetus affected by Rh isoimmunisation
• Monitor antibody titre at booking, 20 weeks, then 4 weekly.
• If antibody titre is >15IU/mL or ≥ 1:32 by ICT, amniocentesis should be carried
out

21. • b) Has history of prior fetus affected by Rh isoimmunisation
• stillbirth or neonatal death
• Severely affected baby (cord Hb < 10g/dL)
• Fetal transfusion in previous pregnancy
• No need for serial antibody monitoring
• 1st amniocentesis or cordocentesis = performed 10 weeks earlier
than the gestation in the previous pregnancy when Rh-associated
morbidity/mortality was first identified (Action line method of
Whitfield)
• Cordocentesis (fetal haematocrit and rhesus status) is preferable < 28
weeks
• If no serious outcome in previous pregnancy, 1st amniocentesis
should be btw 28 and 30 weeks. Repeat in 3 -4 weeks = establish the
trend and eliminate error from bloody tap or from measurement

22. • The concentration of bilirubin in the amniotic fluid
• Spectrophotometry = optical density deviation of 450nm
• Liley’s chart = delta OD450 plotted against GA. Has zones 1-3.
• N.B: Liley’s prediction zones are valid only in 3rd trimester.
• Manage based on the zone
• Biophysical Surveillance
• UltraGFsound to monitor
• Features of hydrops fetalis – ascites, hydrothorax, pericardial effusion, or generalized
edema
• Fetal heart size
• Amniotic fluid index - polyhydramnios
• Fetal movement
• Doppler USS = increase blood flow velocities in umbilical vein, middle cerebral artery
and descending aorta = fetal anaemia

23. • FHR tracing
• Sinusoidal rhythm = severe anaemia
• Abnormal CTG
• Non-reactive
• Reduced variability
• N.B: Clinical and USS features of fetal anaemia only become evident
when fetal Hb >5-7g/dL less than the mean for gestation or become
obvious when the Hb < 5-6g/dL.

24. INTERVENTION
• Depends on result of investigation
• Mildly affected / unaffected fetus
• Zone 1 of Liley’s curve
• Repeat amniocentesis 2-3 weekly
• Deliver near term or after the fetus has achieved pulmonary maturity
• Moderately affected fetus
• Zone 2
• Amniocentesis 1-2 weekly
• Preterm delivery as soon as pulmonary maturity is achieved (naturally or
facilitated)

25. • Severely affected fetus
• Zone 3
• Intrauterine intervention necessary
• Weekly amniocentesis
• Close ultrasound monitoring
• Intrauterine transfusion may be required every 7-10 days until pulmonary
maturity is achieved

26. DELIVERY OF AN AFFECTED FETUS
• Paediatrician should be present.
• - Induction of labour preferable
• - Low threshold for C/S with signs of fetal distress
• - Anaemia predisposes to fetal distress
• - Hypoxia and acidosis impair baby’s ability to conjugate bilirubin
• - Get blood ready for possible exchange transfusion
• - Take cord blood for PCV, blood group and rhesus status, Direct
Coomb’s test, and bilirubin level.

27. POSTPARTUM COUNSELLING AND
CONTRACEPTION
• Counsel patient based on prognosis
• Rh mortality rate range from:
• 2% when no previous baby has been affected to
• 30% when there has been a previous Rhesus death despite intensive
management by experienced Rh team
• Advise on contraception

28. THANKS FOR YOUR TIME