Rhesus

Isoimmunisation
And Hemolytic Disease of the Newborn

Rhesus Isoimmunization
Rhesus (Rh) factor is an antigenic protein
located on RBCs in Rh- individuals.
Transmission is autosomal dominant. When
fetal RBCs leak into maternal circulation,
maternal anti-Rh IgG antibodies can form.
These antibodies can cross the placenta
hemolysis of fetal Rh- RBCs (erythroblastosis
fetalis)
Hemolytic disease usually occurs during the
second pregnancy owing to rapid production of
anti-Rh IgG antibodies by memory plasma cells.

Pathophysiology

Pathophysiology

Rh Sensitisation Requirements
1)
2)

3)

Mother must be Rh ve
Fetus must be Rh +ve which means father
must be Rh +ve
Adequate fetal RBCs must cross over into
maternal circulation to stimulate her
lymphocytes to produce antibodies to the
fetal RBC antigens

Rh Sensitisation Etiologies
- delivery
- prenatal diagnosis (CVS; amniocentesis,
cordocentesis)
- blunt trauma to the gravid abdomen
- antenatal hemorrhage
- external cephalic version
- ectopic pregnancy
- spontaneous abortion
- hydatidiform mole
- vaginal bleeding
- inadvertent transfusion Rh+ blood

Diagnosis - Maternal
On initial visit, test for ABO and Rh
blood groups and perform antibody
screening (indirect Coombs test). If
ve, repeat Coombs test at 2628 weeks. If
+ve, test serially for critical titers of
maternal anti-Rh IgG (> 1:16 to > 1:32).

Indirect Coombs Test Gold

Standard

Diagnosis - Fetal

Assess during pregnancy using amniocentesis

or ultrasound-guided umbilical blood sampling
for fetal blood type, direct Coombs titer, bilirubin
levels, hematocrit, and reticulocytesor determine Rh
status and hematocrit postnatally using fetal cord
blood.
Amniocentesis to determine amniotic fluid bilirubin
levels (delta OD450) had been the traditional method
for indirectly estimating the severity of fetal anemia.
Bilirubin in amniotic fluid derives from fetal pulmonary
and tracheal effluents and correlates with the degree
of fetal hemolysis. (Refer to Liley Chart in Appendix)

Diagnosis - Fetal
Middle Cerebral Artery Doppler
When the critical titer is reached or exceeded
and the fetus isRHD-positive, Doppler
velocimetry of the middle cerebral artery
(MCA) peak systolic velocity (PSV) is
performed to identify fetuses that may be
severely anemic. Doppler assessment of the
fetal MCA-PSV is based on the principle that
the fetal hemoglobin level determines blood
flow in the MCA: MCA-PSV increases as fetal
hemoglobin level falls.

MCA

Immunoprophylaxis
Current recommendations for immunoprophylaxis from the Royal
College of Obstetricians and Gynaecologists and NICE are as
follows:
After delivery, irrespective of the dose of antenatally administered
anti-D immunoglobulin, postnatal prophylaxis must be given and
include a screening test to identify women with a large
fetomaternal haemorrhage who need additional immunoglobulin
Anti-D immunoglobulin should be given after sensitising events
before delivery and after abortion
Anti-D immunoglobulin is no longer necessary in women with
threatened miscarriage with a viable fetus and cessation of
bleeding before 12 weeks' gestation
At least 500 IU of anti-D immunoglobulin should be given to nonsensitised RhD negative women at 28 weeks and 34 weeks of
pregnancy.
Kumar, S. "Management Of Pregnancies With Rhd Alloimmunisation". BMJ 330.7502 (2005): 12551258. Web.

RhoGAM

Contains IgG anti-D(anti-Rho)

and prevents Rh
alloimmunization
Before immunoprophylaxis
became available, HDN affected
1% of all newborns and was
responsible for the death of one
baby in every 2200 births.
Manufactured from human
plasma that contains anti-D
A single 300mcg dose will
suppress the immune response
to 15 ml of Rh-positive RBCs
(approx 30 mL whole blood)
30 mL of fetal blood or 15 mL of
D-positive red cells (only 1% of
women have 5 mL of fetal
blood mixing with maternal
blood after delivery).

Treatment
If the baby is Rh +ve , give RhoGAM postpartum as well.
Give RhoGAM to Rh- mothers who undergo abortion
(therapeutic or spontaneous) or who have had an ectopic
pregnancy, amniocentesis, vaginal bleeding, or placenta
previa/placental abruption.
Sensitized Rh- mothers with titers > 1:16 should be closely
monitored
with serial ultrasound and amniocentesis for evidence of
fetal hemolysis.
In severe cases, initiate preterm delivery when fetal lungs
are mature.
Prior to delivery, intrauterine blood transfusions may be
given to correct a low fetal hematocrit.

Hemolytic Disease of the

Newborn

Maternal antibodies destroy fetal red blood cells

Baby's responds to the hemolysis by trying to
make more red blood cells very quickly in the
bone marrow and the liver and spleen.
Organs enlarge - hepatosplenomegaly.
New red blood cells released prematurely from
bone marrow and are unable to do the work of
mature red blood cells.
As the red blood cells break down, bilirubin is
formed.
Babies unable to get rid of the bilirubin.
Hyperbilirubinemia results in other tissues and
fluids of the baby's body resulting in jaundice.
The placenta helps get rid of some of the
bilirubin, but not all.

Hemolytic Disease of the

Newborn

Severe anemia with

hepatosplenomegaly
When these organs and the bone marrow
cannot compensate for the fast
destruction of red blood cells, severe
anemia results and other organs are
affected.

Kernicterus (CNS damage) - excess of

unconjugated bilirubin > (310-350 mol/L)

Hydrops Fetalis ( protein and

oncotic pressure, edema, jaundice,
high output cardiac failure) occurs
when hemoglobin drops to < 7 g/dL. A
fetus with hydrops is at great risk of
being stillborn.

Summary of Management

Appendix

Management of HDN