RH ISO IMMUNIZATION

RH ALLO IMMUNIZATION

RH NEGATIVE COMPLICATING
PREGNANCY
 Rh- antigen
• Rh- system – LANDSTEINER – 1940
• Rhesus blood group antigens – C, c, D, E, e
• Short arm of chromosome 1
• RH (D) – most immunogenic
• Person lacking D-antigen called Rh-ve
• Lewis and Kell
• 38th day after conception
• INDIA- incidence =8-10%
RH ISOIMMUNIZATION = MAJOR CAUSE OF HEMOLYTIC
DISEASE OF FETUS AND NEWBORN (HDFN)
PATHOGENESIS

FETOMATERNAL
HEMORRHAGE
FIRST PREGNANCY – SENSITIZING PREGNANCY

MOST FMH OCCURS DURING DELIVERY

Weak IgM response

First baby is not affected

Fetal effects of isoimmunization –
non severe
 SUBSEQUENT PREGNANCY – SENSITIZED PREGNANCY

RH POSITIVE FETUS – FMH occurs

AMNESTIC IgG RESPONSE

FETAL CELL HEMOLYSIS

•Congenital anemia of newborn
•Hydrops fetalis
•Fetal Hyperbilirubinemia / ICTERUS GRAVIS NEONATORUM

OUTCOME WORSENS WITH EVERY PREGNANCY

  Rh Antibodies
CRITICAL AMOUNT = 0.1 ml
 Antibodies Coated Red Cells

 Destruction of Fetal Cells by Fetal RES

 Fetal Anemia

 Fetal Hypoxia and Stimulation of Erythropoitin

 Extra Medullary red Cells Synthesis

 Hepato spleenomegally

 Hepatic Cell Failure

 Hypoproteinemia, Increased Intrahepatic

Pressure, Portal hypertension

Ascitis , Edema, hypoxia, Placental

Thickness, Polyhydramnios, Pericardial
effusion
GRAND MOTHER THEORY
 FETO MATERNAL HEMORRHAGE
• Abortion, ectopic pregnancy, molar pregnancy
• Cordocentesis, amniocentesis, chorionic villus
sampling
• Attempted version
5% - First trimester
• Manual removal of placenta 46% - third trimester
• Trauma Maximum (75%) at time of delivery

• Antepartum hemorrhage
• Vaginal delivery, cesarean section, forceps delivery -
<3ml
• Placental abruption
• Blood transfusion
 Risk of sensitization in relation to
volume of FMH
Volume of FMH Risk of
(mL) sensitization (%)
0.1 3
0.2-1 25
>5 65
ABO INCOMPATIBILITY PROTECTIVE
• ABO incompatibility – most common
• HEMOLYTIC DISEASE in newborn
• Very mild anemia
• IGM antibodies – do not cross placenta
• Fetal red cells have fewer A and B antigenic sites than
adult cells- less immunogenic
 Red blood cells is easily destroyed, so not
reaching enough immunological component
to cause antibody response and reaction.
 The risk of sensitization after ABO
incompatible pregnancy is only 2%.

If ABO is compatible:

Rh+ fetal cells  remain in circulation (life

span) until removed by (R.E.S)  destroyed
 liberating antigen (D)  isoimmunization
 Macroph.Antigen
Mother
Presenting Cell Group “O” Rh Negative
T-Hellper
Anti - A Anti - B

B-cell

Anti-D
Placenta

A Rh positive B Rh
“O” Rh positive Positive
Infant
FETAL EFFECTS OF ISOIMMUNIZATION
•Fetal anemia USG
•Hydrops fetalis
•Fetal Hyperbilirubinemia
HEMOLYTIC DISEASE OF FETUS AND NEWBORN
• Hemolysis tolerated by fetus
•Mild anemia and jaundice at birth
•Usually resolves without treatment

• increased circulating bilirubin cleared by placenta

•After birth bilirubin not cleared by immature liver
• hyperbilirunbinemia  Kernicterus
•Moderate anemia – post natal treatment required

• severe fetal anemia

•Hepatosplenomegaly
•Erthryoblasts in circulation
•Liver dysfunction
•Fetal cardiac failure
•Fetal hydrops – stillbirth, neonatal
death
 SIGNS OF FETAL ANEMIA
• Polyhydramnios
• Hyperplacentosis- as an effort to increase the
transfer of oxygen but available fetal red cells
• Fetal ascites
• Hepatosplenomegaly
• Increased right atrial size
• Foetal hydrops(generalised edema)
 Hydrops Fetalis
•Ground glass placenta
•Ascites HALO SIGN

•Pleural effusion

•Pericardial effusion

•Buddha posture

•Halo sign – subcutaneous

edema of scalp

•MCA PSV >1.5 MoM

FETAL DEATH = due to cardiac failure
 MATERNAL EFFECTS OF Rh
ALLOIMMUNISATION
• Hyper placentosis – pre eclampsia
• Cordocentesis ,amniocentesis complications
 MATERNAL MIRROR SYNDROME
Ballantyne
syndrome

Swollen baby
Swollen placenta
Swollen mother !
ROUTINE ANTENATAL MANAGEMENT
OF NORMAL SINGLETON PREGNANCY
BABY

MOTHER
 DETERMINING FETAL Rh factor
• Non invasive fetal testing for Rh D gene
• Cell – free fetal DNA (cfDNA) in maternal
plasma
 SCREENING OF ALLO IMMUNISATION
• In the first pregnancy:
 At first booking
 20 weeks
 28 weeks
• In subsequent pregnancies
previous pregnancy with no or mild hemolytic disease
1. At first booking
2. Every 4-6 weeks subsequently
 Previous pregnancy with severe hemolytic disease
1. Titre not required
2. Testing for fetal anemia beginning from 16-18 weeks
 ICT = NEGATIVE

NO ISOIMMUNIZATION AT PRESENT

AIM:
Minimizing chances of FMH
Preventing alloimmunization – Anti D

ANTI – D
•28 weeks of gestation – ICT NEGATIVE
•within 72 hours of delivery – RH POSITIVE FETUS -DCT
NEGATIVE - atleast within 13 days
 ANTI – D
•IgG antibody

•Binds to fetal RBCs and prevent

stimulation of maternal immune
system

•POLYCLONAL (MOST COMMON)

•300mcg = 15 ml of fetal RBCs

= 30 ml of fetal blood

•50 mcg = 2.5 ml of fetal RBCs

•Half life = 16-24 days

•IM – Deltoid/ Anterolateral aspect

of thigh
 Dose of Anti D ≈ Amount of FMH
KLEIHAUER BETKE TEST / ACID ELUTION TEST
• Sample: Maternal blood
• Principle : HbF is more resistant to acid elution than HbA
MBV x maternal Hct x %fetal cells in KB
Fetal blood volume = ---------------------------------------------------------
Newborn Hct
• 100mcg of Anti D neutralise 4ml of fetomaternal blood

Flow cytometry
 Maternal red cells/ ghost
cells

Dark red fetal cells

 FETO MATERNAL HEMORRHAGE
Indications Recommended Dose (mcg)
First trimester abortion/ 50
MTP
First trimester ectopic 50
pregnancy
Second trimester 300
abortion/MTP
Second trimester 300
300 mcg = 1500IU
amniocentesis
Prophylaxis at 28 weeks 300

After delivery 300

 ICT = POSITIVE

Rh ISOIMMUNIZED PREGNANCY

Assess Antibody titre

CRITICAL TITRE = 1:16
< 1:16 > 1:16
MONITOR
FETAL
ANEMIA
ICT EVERY 4 WEEKS
< 1.5 MoM >1.5 MoM

>34 weeks >34 weeks

FETAL BLOOD
DELIVER SAMPLING

HEMATOCRIT <30% HEMATOCRIT >30%

WEEKLY FBS, depending

on MCA-PSV
 SERIAL AMNIOCENTESIS AND LILEY
CURVE
• Hemolysis  high levels of bilirubin into
amniotic fluid
• Amniocentesis done
• Amount of bilirubin is quantitated by
spectrophotometrically measuring delta
optical density (∆OD 450nm wavelength)
LILEY’S CHART
 Serial Amniocentesis

Lily zone I Upper Zone II Zone III

Lower Zone II Hydramnios & Hydrops

Repeat
Fetal blood sampling
Amniocentesis every
2-4 weeks
Fetal Fetal
hematocrit<30% hematocrit>30%
Delivery at OR near term

Intrauterine
Transfusion
Repeat Amniocentesis in 7 Follow with fetal
days or FBS Blood sampling
& USG
Hct < 30% Hct > 30%

DELIVERY
Intrauterine Repeat Sampling
WHEN LUNG
Transfusion 7 to 14 days
MATURE
Suggested management after amniocentesis for ΔO D 450
 FETAL MIDDLE CEREBRAL ARTERY
PEAK SYSTOLIC VELOCITY
• Presently used Fetal anemia
Normal
 INTRA UTERINE TRANSFUSION
• HCT <30%
• O Negative
• Crossmatched with mother’s blood
• Tightly packed to achieve hematocrit of 75-85%

ROUTES

INTRA- INTRA-
VASCULAR PERITONEAL

Intra hepatic
Umbilical vein at Diaphragmatic
portion of umbilical
cord insertion lymphatics
vein
INTRA UTERINE TRANSFUSION
MANAGEMENT DURING DELIVERY

Indication for LSCS:

 Severe form of hemolytic

infant disease in the term
or 34-35 weeks after
previous antenatal
prevention of fetal hyaline
membranes syndrome;
Measures to be taken during LSCS
 prevent spillage of blood from the placenta
to into the peritoneal cavity.
 Spontaneous delivery of placenta using
control cord traction without squeezing the
uterus.
Avoid avulsions of the cord.
Vaginal delivery in Rh-
isoimmunization
 undergo delivery in
the term of 37-38
weeks of gestation.
 Induction of labor is
performed by
prostaglandin (in the
case of “unripe”
uterine cervix) or by
intravenous oxytocin
infusion
administration (in the
case of “ripe” uterine
cervix).
 Vaginal delivery in Rh-isoimmunization
 During labor:
 No fundal pushing in 1st or 2nd stage of labor.
 Withhold inj methergin after ant. shoulder delivery.
 Early cord clamping and no milking.
 No uterine massage or squeeze in 3rd stage.
 Let the placenta to be delivered spontaneous to
avoid avulsions of the cord.
 Protect the vaginal and perineal wounds and
laceration from being exposed to the fetal blood spilled
from cord
 At birth
 Maternal blood

a. antibodies by indirect Comb's test ( ICT )..

b. fetal red blood cells in maternal circulation

 Cord blood sample ( Neonatal blood sample ) for
a. antibodies by Direct Comb's test ( DCT )
b. Infant blood group and rh-typing.
c. Infant bilirubin level
d. Infant Hb & Hct level
 Management of sensitized
newborn
Mild anemia (Hb <14gm/dl,
cord bilirubin>4 mg/dl)---
Phototherapy
-Moderate to severe----
Exchange
transfusion.
-Mild Hydrops improves in
88% of cases
-Severe hydrops—Mortality is
39%