Rhesus Isoimmunization

Ishen Perumal
A 29yo G2P0+1 presents at 12 weeks gestation f
or antenatal care.Had a miscarriage for an unpla
nned pregnancy as a teen but never sought med
ical help at the time. Routine scan-viable pregna
ncy consistent with dates. Her blood group is A R
h- and an antibody screen positive for anti-D at t
itre of 1:8. Outline your management for this pt,
as well as the potential complications for this an
d subsequent pregnancies.
 Rhesus iso-immunization
•Blood groups
-ABO
-Rhesus
-dan lain-lain (over 200)

Mismatch between mother and fetus can lead

to HDFN
•Rhesus antigens
-C,c,E,e,D

•Only Anti-D and anti-c cause HDFN

- D is much more common
• HDFN – Hemolytic disease of the fetus and ne
wborn (HDFN) refers to hemolysis of fetal or ne
onatal RBCs by maternal alloantibodies to a fet
al RBC antigen. Previously called hemolytic dise
ase of the newborn (HDN).

• Hydrops fetalis – The most severe manifestati

on of HDFN, in which severe anemia and extra
medullary hematopoiesis in the liver and spleen
lead to heart failure and generalized edema (hy
drops).
HDFN as a result of Rh isoimmunization invo
lves 3 stages

Rh negative mother and Rh positive fetus

Fetal cells gain access to maternal circulation in

sufficient volume

Maternal antibodies cross placenta and cause

immune destruction of RBCs in fetus.
 Potential sensitizing events for Rhesus disease

The development of anti-D antibodies usually occurs as a

result of fetomaternal haemorrhage (FMH) in a
rhesus D (RhD)-negative woman with an RhD-positive fet
us.

Other events

●Injection with needles contaminated by Rh(D)-positive

blood
●Inadvertent transfusion of Rh(D)-positive blood
●D-mismatched allogeneic hematopoietic stem cell trans
plantation
Rhesus antigens are well expressed by fetus at 30-
40 days gestation

Fetal hemolysis occurs when IgG is present in suffic

ient quantities in the fetal circulation, leading to se
vere anemia.

Usually first pregnancy not affected

-IgM produced, does not cross placenta
 Assessment
History
Rhesus negative woman – ask about previous pr
egnancies- was Ig given? Any invasive procedure
s? C section? Miscarriage? Instrumentation to ute
rus? Ectopic? Etc. (events that could lead to FMH)
History of blood transfusions?
Ask about partner-blood group? Confirm father
of fetus.

PE
Signs of anemia?
Polyhydramnios?
Evaluation of maternal ABO blood group, Rh typ
e and anti D antibodies (indirect Coombs test) sh
ould be detected at every first prenatal visit.

The diagnosis of Rh(D) alloimmunization is base

d upon detection of anti-Rh(D) antibody in mate
rnal serum.
-Indirect Coomb’s test
• Women who are Rh D negative with a positive
anti D antibody screen test are considered Rh a
lloimmunized 
• In general, women with titers higher than 1:4 s
hould be considered Rh alloimmunized.
Investigations
•  Diagnostic - Indirect Coombs test - determinat
ion of antibodies in the plasma
• Gel Microcolumn Assay (GMA) card - alternative to
traditional tube agglutination tests for determining
anti-D antibody titers.
• To quantify FMH
- Kleihauer test
- Flow cytometry
 Prevention
Post
Anti D exposure
prophylaxi
s Routine

Anti-D immunoglobulins ‘mop up’ any circulating rhesus-positive cel

ls before an immune response is excited in the mother.
An intramuscular dose of 500 iu of anti-D Ig will neutralise an FMH of up to 4 ml. For e
ach millilitre of FMH in excess of 4 ml, a further 125 micrograms of anti-D Ig is nece
ssary *1 mcg = 5 IU
Post exposure prophylaxis

Anti D Ig IM asap(within 72 hrs) after exposure

to fetal red cells (FMH)

Below 20 weeks : 250IU minimum

After 20 weeks : 500IU minimum
+ Kleihauer test

Recurrent vaginal bleeding/Threatened miscarria

ge
-anti D at 6 week intervals from 12 weeks
For miscarriage
• Anti-D Ig should be given to all non-sensitised RhD-nega
tive women who have a spontaneous complete or incom
plete miscarriage at or after 12+0 weeks of gestation.
• Anti-D Ig is not required for spontaneous miscarriage bef
ore 12+0 weeks of gestation, provided there is no instru
mentation of the uterus or pain.
• Anti-D Ig should be given to non-sensitised RhD-negative
women undergoing surgical evacuation of the uterus, reg
ardless of gestation.
• Anti-D Ig should be considered for non-sensitised RhD-ne
gative women undergoing medical evacuation of the uter
us, regardless of gestation.
Prevention (continued)
• Routine prophylaxis – Dosage (HKL)
Either
2 doses of Anti D Ig 500IU at 28 and 34 weeks
OR
1 dose of Anti D Ig 1500IU at 28-30 weeks

Administration of anti-D immune globulin postnatal is wi

thin 72 hours of delivery of an Rh(D)-positive infant
1500IU minimum + Kleihauer test

*1 mcg = 5 IU
• Once alloimmunization has occurred, anti-D im
mune globulin is not effective for preventing or
reducing the severity of fetal/neonatal disease.
MANAGEMENT OF PREGNANCIES COMP
LICATED BY ALLOIMMUNIZATION

•Determine fetal Rh type

• Titres performed monthly until 24 wks, then fortnightly
• if the titer is 1:16 or higher, fetal wellness assessment is m
andatory

•Monitor for fetal anemia

- Maternal anti D titers
- Ultrasound – fetal middle cerebral artery peak systolic v
elocity
- Amniotic fluid delta OD 450
- At 18 weeks
 Severe fetal anemia
•Near term (35 weeks or more)
-delivery – neonatal treatment

•Far from term(<35 weeks)

-Intrauterine fetal transfusion
After 1st pregnancy
• Severe anemia manifests earlier in subsequent preg
nancies
• determine fetal RHD type using cfDNA and a baselin
e maternal titer early in gestation.
• measure MCA-PSV weekly, beginning at 16 to 18 we
eks gestation.
•Hematologist
•Pediatrician/Neonatologist
•Patient should be given written information (le
aflet, etc) about her condition, risk in future pre
gnancies

•In general, patients should be given written inf

o to make an informed decision about routine
antenatal anti-D prophylaxis (RAADP). Consent
should be recorded.