This ppt may help in understanding Rh negative women during pregnancy, labour and postpartum. Great advancements have been made in the detection and management of this condition, and many of our Rh-negative women can now have a happy obstetric career.
6. Most immunogenic, Most common
90% Positive; 10% Negative
D – antigen – the ‘BIGG BOSS’
16 Epitopes
7. Over 50 different Rh antigens
6/50
D C c E e G
G – It is an unique antigen, having properties of both Antigen D
and C because one amino acid is different from both of these.
6- Rh factors
8. D
Rh +ve
G
D
Rh -ve
Immune response C/D
(As they share the same property of C/D)
Consider her as Rh +ve
Anti-D to be given
g– antigen
9. “WEAK-D” ANTIGEN / D ANTIGEN
u
Normal D Ag but expression weakened
Partial D-Antigen (small portion of D Ag missing)
Lab 1 report- Rh +ve Lab 2 report- Rh -ve
D
u
16. alloimmunisation
Immune response (development of antibodies) in an individual
of one species to an antigen from a different individual of
the same species.
ISO
AUTO
Same as Allo
One’s own antigen
17. RH ALLO-IMMUNISATIONIN PREGNANCY
Immune response (development of antibodies) in a mother by
Rh antigen from her fetus.
SENSITISATION
Immune response (development of antibodies) in a mother by
Rh antigen from her fetus for the first time.
18. PATHOPHYSIOLOGY
• The amount of foetal blood necessary to produce Rh
incompatibility varies, but as little as 0.1 ml of Rh+ cells have been
documented
• Therefore, the critical sensitizing volume (CSV – 0.1ml)
Studies have suggested that up to 30% of persons (non-
responders) with Rh- blood never develop Rh incompatibility
even when challenged with large volumes of Rh+ blood
19. Rh alloimmunisation occurs by 1 of 2 mechanisms
After incompatible blood transfusion
After foeto-maternal haemorrhage between mother and an
incompatible foetus
Foeto-maternal haemorrhage may occur during pregnancy (10%) or
delivery (90%)
Foetal RBCs have been detected in the maternal blood in all three (7, 16,
29%) trimesters without an apparent predisposing factor
20. The initial maternal response to Rh sensitisation is low levels of IgM Ab (Saline Agglutinating a/b)
- These are confined to maternal circulation being unable to cross the placental barrier (size - big)
970kDa
Within 6 weeks to 6 months, IgG Ab are formed (size- small 150kDa)
These are able to cross the placenta and destroy foetal Rh-positive cells
Therefore, first-born infants with Rh-positive blood type are not affected
The short period of 1st
exposure of mother to foetal RBCs is insufficient for production of
significant IgG Ab response
Subsequent pregnancies may trigger a rapid & robust Ab response - Anamnestic response
Anamnestic theories:
– Grandmother theory
– “Sensibilization” theory
21. Sequence of inutero events
Maternal IgG enters foetal circulation via placenta
Destruction of foetal red cells occur - foetal anaemia [HCT<30%]
Haem is formed and converted to bilirubin – foetal
hyperbilirubinaemia
Both are neurotoxic, but effectively cleared by placenta and
metabolised by the mother
Extramedullary erythropoeisis is stimulated
Immature erythroblasts are produced
22. When cell destruction exceeds production
Severe anaemia occurs
More demand on extramedullary sites to produce more red
cells – hepatosplenomegaly
Heart failure eventually results, with ascites, oedema and
pericardial effusion – erythroblastosis fetalis
Hydrops fetalis, occurs when the haematocrit falls below 15%.
Often results in IUD and still birth
23. The risk and severity of sensitisation response increases with
each subsequent pregnancy involving an ABO-compatible foetus
with Rh-positive blood
Without prophylaxis, risk is:
16% after two deliveries;
1.5-2% occur antepartum
7% within 6 months of delivery
7% manifest early in 2nd pregnancy
With prophylaxis, the risk drops to 0.1%
24. Therefore, mentioned risk depends on the 3 main factors:
Volume of transplacental haemorrhage
Extent of the maternal immune response
Concurrent presence of ABO incompatibility (protective –
risk drops to 1.5-2%)
Rh incompatibility is only of medical concern for females who
are pregnant, or plan to get pregnant in future
25. EFFECTSON A MOTHER
• Polyhydramnios
• PPH
• Placentomegaly
• Mirror syndrome- triple edema
Edema of mother/placenta/baby
27. INVESTIGATIONS
Hydrops occurs at Hb deficit of 7gm%
CTG- Sinusoidal pattern
X RAY- Buddha position- Halo around head due to scalp edema
USG-
1. Placentomegaly- Placental thickness > 4cm (2nd trimester)/
>6cm (3rd trimester)
2. Increased AC (due to hepatosplenomegaly)
3. Increased blood flow through umbilical vein- umbilical vein diameter >5mm
and can find fluid in serious cavities.
1st site of fluid collection- Pericardium
4. Cardiomegaly- Cardiac circumference/ Thoracic circumference >50% and
1st heart chamber to enlarge- RA
34. 1. HOW DOES ANTI –D WORK?
Binds D-antigen sites on fetal RBCs in the maternal circulation
and does not destroy the RBCs and cause haemolysis
ANTI D PROPHYLAXIS
35. Prevents their immune recognition of bound RBCs by B
lymphocytes in maternal blood. Production of IgG blocked
36. • FOGSI guidelines recommends- Routine Antinatal, Anti-D, Prophylaxis
(RAADP) in all non- sensitised Rh –ve pregnancy at 28 weeks
• Informed consent needed (blood product)
• Cold chain to be maintained less than 8 degree (needs refrigeration but not
to be freezed )
• If in room temperature, it is to be used within 4 hours
• Site of injection deep im- intra deltoid
Intra gluteal is not advised. If needed, can be given to anterio lateral part of
the thigh
• I.V. cannot be given due to Risk of Anaphylaxis (blood products)
37. • 1 microgram=5 IU; 300 microgram=1500 IU
• In 1st trimester missed abortion – 50-100 micrograms (5-10ml FMH)
• In 2nd and 3rd trimester – 300 micrograms
• 300 micrograms- at 28 weeks (D antigen is not expressed before 28.
If FMH sensitises, it will be less than 0.1%)
• In molar pregnancy – 300 micrograms (partial/complete mole is difficult to
be diagnosed in early pregnancies. So, even if no fetal tissue/ no RBC, Anti-
D is recommended )
• In DIC, consider s/c route (risk of hematoma)
• After tubal ligation, guidelines suggest “ Neither necessary or cost
effective”. But, recommended Anti-D (in view of recanalization/further
conceptions)
• After Anti-D, ICT becomes +ve after 6-12 weeks (low titer – 1:4)
• In IUFD, Anti-D 300 microgram to be given before induction of labour
39. • If delivery occurs within 3 weeks of the dose of Anti-D or FMH <
15ml (K/B test) Anti-d not required.
• If FMH > 15ml, then calculate :
Keihauer Betke Test
40.
41. Monoclonal Anti – D immunoglobulin
• Highly specific antibodies against
single antigenic epitope produced
by the clone of a single hybrid cell
formed in the laboratory by the
fusion
• Advantages
• Specific
• Consistent
• Uniform
• Safe from transmission of viruses
and harmful proteins
42. FEATURES-ADVANTAGES-BENEFITS
Undoubted safety
Uniformity of
product with
competitive
pricing
No risk from
emerging diseases
like CJD, Parvovirus
infection
Superior
technology
No pooled
plasma
involved in
manufacturing
process
Higher specificity
of action
No shortages
unlike polyclonal
Anti-D
Provides
monoclonal Anti-D
No batch to batch
variation
Unlimited
production
Manufactured
by hybridoma
technology
BENEFITS
ADVANTAGES
FEATURES
43. Polyclonal Anti – D immunoglobulin
• Polyclonal-derived from sera of immunized humans,
made up of mixture of antibodies with affinity for a
wide range of antigenic epitopes
• Difficult to manufacture in large quantities
• Difficult to provide consistent batches
• Chances of transmission of infection and harmful
proteins
52. KELL ANTIBODY
• Incidence 1-3%
• SENSITISATION- Only by BT
• It attacks precursors of RBC in bone marrow causing
anemia
• No haemolysis/jaundice
• Diagnosis- Antibody identification-
MCA/PSV
• “KELL KILLS”
67. Value below which no case of fetal hemolysis
has been Reported
Most labs test for titers by the Gel method
Critical titers by Gel method – Lab dependent
Critical Titer 1:16 (Tube Method)
68.
69.
70.
71. Plan of management if ICT –ve
Booking ICT –ve
Repeat ICT
28 and 34 weeks
ICT –ve
Give Anti-D prophylaxis at 28-32 weeks
Weak D (known as DU +ve need not receive Anti-D)
Deliver at 40 weeks
Anti –D prophylaxis within 72 hours of deliver
72. ICT+VE
Critical Titer – 1:16 (tube method)
< 1:16 > 1:16 WARNING
Rpt titer every 4 wks
Anti-D at 28-32 wks
Rpt Anti-D within 72 hours
of birth if baby is Rh +ve
Monitor every 2 wks
Fetal USG (20 wks onwards)
MCA/PSV and features of
hydrops
73. Middle Cerebral Artery Doppler (MCAD) Velocimetry
• Accurate and non-invasive screening tool for detecting moderate
to severe foetal anemia
• A sensitivity of 100% and a 12% false positive rate for anemia
• Use has resulted in up to 80% reduction in invasive testing(i.e.,
amniocentesis, cordocentesis)
• Not useful before 18 weeks of gestation – RES too immature to
haemolyse enough cells to cause significant anemia
• Not a reliable predictor of severe anemia
after 35 weeks of gestation
GOLDSTANDARDTO DIAGNOSEISOIMMUNISEDFOETALANEMIA
74.
75. MCA- is opted as this was 1st described by Mary’s chart
based on Doppler Equation which calculates angel as 0
In MCA- It is easy to get an angel of 0 between the USG
beam and direction of blood flow.
The pulsed-wave Doppler gate should then be placed at the
proximal third of the MCA, close to its origin in the internal
carotid artery(the systolic velocity decreases with distance
from the point of origin of this vessel).
76. • Care should be taken to avoid unnecessary pressure on the fetal head.
• At least three and fewer than 10 consecutive waveforms should be recorded. The
highest point of the waveform is considered as the PSV (cm/s).
• PSV is gestational age dependent. So, absolute value is converted to MOM-
Multiples Of Median
• >1.5 MOM – indicates severe anemia
• We have calculations available in USG softwares/perinatology.com website
77.
78.
79. INTRAUTERINE FETALTRANSFUSION
• Indication-
Before 26 wks POG- Hematocrit <25%
After 26 wks- HCT<30%
Zone 3 of Liley’s charts
• Routes- Intravascular, Intraperitoneal, Combined Intracardiac
• Intravascular
1. Site- umbilical vein at placental insertion site
2. Done using 20-22 G spinal needle
3. Blood used- ABO identical of fetus (if known)> O negative
Cross matched with mother’s blood
Irradicated to prevent any viral infection
Leucodepleted to avoid GVH reaction- done with gamma rays, RCBs lack DNA and hence not affected
4. Packed to a HCT of 80-90% to achieve fetal HCT of 50%
5. Amount of blood- (Final HCT-Initial HCT)/HCT of transfused blood *fetal placental volume (usually
transfuse 40-60ml of blood at one time)
6. Repeated when HCT falls below 30%
7. Can be started at 18 wks, repeated 1-2 weekly till 34 weeks
• Intraperitoneal- if POG<18wks, absorbed by subdiaphragmatic lymphatics
80.
81.
82.
83. Invasive procedures for fetal testing is decreasing
• Amniocentesis – Fetal loss = 0.1-1.4%
PPROM = 1-2%
Needle injuries = 0.1%
Vaginal bleeding = 10%
• Prophylactic Anti-D should be given to n on-sensitised
women within 72 hours post procedure unless the alleged
father of the fetus is proven also to be Rh –ve.
84. Choose time of inductionand the best method of delivery
• Balance the risks of prematurity (too soon) with that of
worsening Rh disease (too late)
• Consider the risks of vaginal delivery and be prepared for a
lower segment Caesarean section (LSCS)
• Usually done only after 34 weeks of gestation
• The paediatric team should be present at the delivery
• Fresh Rh-negative blood available
86. MEASURESTO BETAKENduring vaginal delivery
During Labor -
• No fundal pushing in 1st or 2nd stage of labor
• Withhold inj methergine after ant.shoulder delivery
• Early cord clamping and no milking
• No uterine massage in 3rd stage
• Spontaneous delivery of placenta to avoid avulsion of the cord
• Protect the vaginal and perineal wounds and laceration from
being exposed to the foetal blood spilled from cord
Cord Blood Sample -
DCT/ Baby blood group and Rh type/ Hb/ bilirubin / HCT/ P-smear
87. MEASURESTO BE TAKENDURINGlscs
• Prevent spillage of blood from the placenta into the
peritoneal cavity by packing paracollic gutter with mops
• Allow spontaneous delivery of placenta/ control cord
traction without squeezing the uterus
• Avoid avulsion of the cord
• Early cord clamping and no milking
88. Post Delivery
• Psychological support
• Educating about the need of Anti-D injection
• Consent if they are not willing for Anti-D injection
• Counselling for further conceptions
89. RESUSCIATION AND EXCHANGE TRANSFUSION
• Good resuscitation is essential. In an anemic and premature infant, lung
disease is common. It can be due to:
SURFACTANT DEFICIENCY at very early delivery
PULMONARY OEDEMA from anemia and hypoproteinemia
HYPOPLASTIC LUNGS secondary to pleural effusions
• In severe Rh haemolytic disease of the newborn, an umbilical artery
catheter should be inserted as soon as possible to assess and control PaO2
and pH
• Central venous pressure should be measured
Drain pleural effusions and ascites at resuscitation
90. PHOTOTHERAPY
- Mild anemia (Hb<14gm/dl, cord bilirubin > 4mg/d)
• Placing newborn under a halogen or fluorescent lamp with
their eyes covered
• Lowers the bilirubin levels in the baby’s blood through photo-
oxidation
• During phototherapy, intravenous hydration is require
Exchange transfusion
- Moderate Anemia
- mild hydrops improves on 88% cases
- Severe hydrops mortality – 39%
91. Recent Advances
• cffDNA is fetal DNA that circulates freely in maternal blood
• cffDNA originates from placental trophoblast and is present after 5-7 wks of
gestasion
• Fetal DNA is fragmented when placental microparticles are shed into maternal
blood circulation
• cffDNA fragments are approximately 200 base pairs in length – they are smaller
than maternal DNA fragments
• The difference in size allows cffDNA to be distinguished from maternal DNA
fragments
• Genotype can be done at 16 wks (KELL-20wks)
• It is reasonable not to perform fetal genotype until antibody reaches a level that
would warrant MCA monitoring
92. Problemin our setting
• High cost of the immunoglobulin
• Lack of resources to adequately investigate and monitor
fetus inutero
• Low turnout for antenatal clinics – missed cases
• Poor documentation of prior sensitizing events – some are
yet to fully grasp the import
• Loss of case notes
93. RECOMMENDATIONS
• Advocacy for partnership by government and NGOs to
help subsidize the cost of the immunoglobulin
• Special insurance cover for Rh negative women to ensure
ease of procurement when needed
• Involvement of clergy as part of pre-marital counsellors
• Creation of special for a/groups for Rh-negative people
where potential Rh-negative spouses can be met
94. conclusion
• Rhesus alloimmunization is a real problem and real efforts
need to be made to mitigate its impact
• Although its incidence has decreased dramatically, yet the
consequences of haemolytic disease of the newborn
remain
• Great advancements have been made in the detection and
management of this condition, and many of our Rh-
negative women can now have a happy obstetric career
