Rhesus

Isoimmunization

Objectives
Definitions
Incidence
Aetiology
Pathophysiology
Management of the Rhesus Negative
mother with a Rhesus Positive fetus

Definitions
Isoimmunizaion
This is the production of
antibodies by an individual
against antigens that
originate from a different
individual of the same
species.

Rhesus
Isoimmunization
The production of maternal
antibodies to the D
antigen present on fetal
red blood cells.

Blood Groups

35 human blood group

systems
ABO
Rhesus Blood Grp
Most important
system after the
ABO group

Expressed on
chromosome 1
Rhesus: Over 50 antigens
Five important
antigens: D, C, c, E
and e
D is most
immunogenic
Expressed clinically as:
Rh positive (Rh+ if
the D antigen is
present)
Rhesus negative
(Rh- : the D antigen

Country and Percentage of Rh Prevalence

Asia
ns

Caucasi
ans

Taiwan
Phillipines
Japan
Indonesia
China
Nigeria
Jamaica
Israel
Russia
Canada
USA
Poland
France
Australia
Brazil

0.23
0.33
0.5
0.5
0.63
3
7
10
11.9
14.9
15
15
15
19
19.5

Rhesus Prevalence
Prevalence of Rhesus Negative Blood Types among race
Race
Caucasians
African Americans
Asian

Prevalence
15%
6%
<1%

Rhesus:
Distribution of Blood Types in Jamaica

O+ 47%
A+ 23%
B+ 20%
AB+ 3%
O- 3.5%
A- 2%
B- 1%
AB- 0.5%

Affects a total % of 7%
of the population

Source: National Blood Transfusion

Service

Rhesus Inheritance Patterns

50:5
0

25:
25

50:

Aetiology: Rhesus Isoimmunization

Prepregnancy

1st Trimester

2nd trimester 3rd Trimester

Blood
Transfusions

Ectopic
pregnancy

Dilatation and Placental

curettage
separation at birth

Unrecognized
pregnancy
losses

Spontaneous
miscarriages

Placenta praevia

Amniocentesis

Placental
abruption

Chorionic
Villous
sampling

External
cephalic
version

Cordocentesis
Induced

Aetiology: Rhesus Isoimmunization

In 55-80% of cases there is

no identifiable cause of
rhesus isoimmunization, and
sensitization is silent,
secondary to occult
fetomaternal hemorrhages

RCOG, revised 2002 guideline on Rhesus D Prophylaxis

Pathophysiology

Blood production +
fetal circulation
3 4 weeks
respectively

Maternal sensitization
and immunization can
occur early

Rhesus antigen
detected on
erythrocyte
at 38 days

Before 12 weeks
Low risk
As little as 1mL of
blood may stimulate
isoimmunisation.

Pathophysiology

Rh- mother with

Rh+ Fetus

Feto-maternal
Haemorrhage

Fetal Cells interact with

Maternal Circulation

Complications
Haemolysis

Categorized
as mild,
moderate or
severe:

Mild
little to no anaemia
may exhibit
hyperbilirubinaemia only
Moderate
marked anaemia
marked hyperbilirubinaemia/jaundice
marked reticulocytosis haemolysis
persists with erythropoiesis trying to
compensate

Complications contd
SEVERE
Decompensating fetal
compartment
Extra-medullary
erythropoiesis in the
spleen and liver
Erythroblastosis
Fetalis

Kernicterus
Portal Hypertension
Placental Oedema
abnormal placental
perfusion ascites in
the fetus
Liver damage
progresses albumin
production fluid
extravasation leading to
anasarca and effusions

Complications contd
Hydrops Fetalis
preceded by
hepatomegaly,
increased placental
thickness and
polyhydramnios

Still Birth

Haemolytic Disease of the

Newborn/Erythroblastosis Fetalis
Maternal IgG production
rapidly crosses the
placenta and coats fetal
Rh+ rbc
Extravascular
destruction takes place
in the fetal spleen)
Compensatory
erythropoiesis by the
fetal liver and spleen

Erythroblastosis Fetalis

Erythroblastosis Fetalis

Kernicterus
Deposition of bilirubin
in the grey matter of
the fetus
Normally, bilirubin is
cleared from the fetus
via the placenta and
maternal circulation
Due to excess
haemolysis and
bilirubin production
this clearance is
impaired
Bilirubin then crosses

Usually occurs within

days of birth of the
infant
Features include: Loss of the Moro reflex
Posturing
Poor feeding
Inactivity; bulging
fontanelles; high
pitched shrill cry;
seizures
Long term sequelae
may develop:
hypotonia, hearing
impairment, mental
retardation

HydropsFetalis
Classified:
Accumulation of fluid
or oedema in at least
two (2) fetal
compartments
subcutaneous
tissue/scalp
pleura (effusions)
pericardium
(effusions)
abdomen (ascites)

immune or nonimmune
Rhesus
isoimmunisation is
an immune cause
Fetus
pale
low haematocrit
Death
can occur shortly
before or after birth
unless an exchange
transfusion is done

MANAGEMENT

Recognition of AT-Risk Pregnancy

A blood sample is
taken for ABO and
Rhesus grouping at
the booking visit
The Rhesus group
of the father
maybe necessary
to determine if the
fetus is at risk

A complete and
thorough history is
NECESSARY
Previous blood
transfusions
Previous early pregnancy
bleeding or terminations
(miscarriages, ectopic)
Delivery of viable fetus
Prior sensitization
Was Rh-immune globulin
given post delivery?

Has Feto-Maternal Haemorrhage

Occurred?
Determined using the
Kleihauer-Betke
test/acid elution test
Flow Cytometry is an
alternative

Indirect Coombs Test

Determining Fetal Rhesus

Status
Invasive Methods

Amniocentesis
Cordocentesis

Non-Invasive Methods
Doppler Ultrasound
Flow Cytometry sorts
fetal cells from
maternal blood
DNA amplification using
a single fetal nucleated
erythrocyte
Determination of free
fetal DNA in maternal
plasma/serum

Determining Fetal Rhesus

Status
Invasive Methods
Amniocentesis
The most common method
employed is
Under ultrasound guidance,
a sterile 22 gauge needle
into a pool of liquor and a
sample is obtained
Fetal red cell antigen typing
is then done on amniotic
cells present in the sample
Risk of amnionitis and
preterm labour are a cause
for concern

Spectrophotometry

The Liley Chart

Cordocentesis
NOT first line
Provides accurate
diagnosis
Experienced practitioners
Haemorrhage (40%)
Exsanguination and
death
22 gauge spinal needle
Fetal Hb, haematocrit,
blood gases, pH, and
bilirubin levels

Non-Invasive Fetal Monitoring

Doppler
ultrasound
Assess peak
velocity in
Middle
Cerebral
Artery
(cm/min)
Valuable tool
for detecting
fetal
anaemia

Ultrasound Assessment
Determines Fetal:-

Liver size
Spleen size
Placenta size
Features of Fetal Hydrops

Intrauterine Transfusion
When?
Why?
How?
Repeated every 1-2
weeks to keep fetal
haematocrit above
30%

Survival rate:
Overall: 85%
Fetuses with no
evidence of Hydrops:
90%
Fetuses with
Hydrops: 75%

Rhogam
Rhesus Immune Globulin
Pools of fractionated human
plasma (sensitized donors)
EXPENSIVE
Preferred means of preventing
Rh isoimmunisation
Given mostly in postpartum
period
1-2% risk of failure due to
antepartum sensitizing
events

Indications and
Contraindications
Indications:
All the sensitizing
events mentioned
previously
Routine antenatal
administration to
non-sensitized Rhmothers.

Contraindications:
Patient refusal
Rh- mothers with
known Rh- fetus
Rh- mothers who
have already been
immunized

Dosing
According to the Royal
College of Obstetricians
and Gynaecologists,
Green-Top Guideline No.
22, March 2011: - 500 IU will neutralize
an FMH up to 4mL. For
each 1mL in excess,
add 125 IU
- less than 20+0 weeks:
250 IU

20+0 weeks: 500 IU

- Must be given in the
deltoid muscle
- 12+0 weeks:
Rhogam is administered
for spontaneous,
complete or incomplete
miscarriages.

Routine Antenatal
Prophylaxis
Given as a single dose
at 28 weeks gestation
or a split dose at 28
and 34 weeks
gestation.
RCOG states 500 IU at
28 and 34 weeks or
1500 IU at 28 weeks
only
At UHWI 350 mcg (1500
IU) are given at
delivery/ within 72
hours

No evidence that
single or double
dose differ in
efficacy

Timing of Delivery
While the goal is a term neonate, the risks
for intrauterine demise must be balanced
against the risks of prematurity.
After 34 weeks, the risk of intrauterine loss
is great
Ensure lung maturity before delivery with
dexamethasone or betamethasone
Careful fetal monitoring is crucial if
prolongation of intrauterine life is deemed
appropriate beyond 34 weeks

Post Partum Rhogam Administration

Should be given within 72
hours of delivery
Some efficacy even after 72
hours so do not withhold if
this time has passed
At least 500 IU are given to
non-sensitized Rh- women at
delivery
Quantify FMH above 4 mL so
additional Anti-D can be
administered

Summary
Although, Rh isoimmunization is relatively low in
incidence, when it does occur the consequences
are very severe to mother and baby.
Therefore, it is important to identify those who
at risk
Monitor closely so that steps can be taken to
save the babys life and spare the mother and
family from fetal demise

References
http://
www.embryology.ch/anglais/pcardio/umstellung01.html#fetalerkreisl
auf
http://
www.gfmer.ch/SRH-Course-2010/national-guidelines/pdf/Managemen
t-Rhesus-Negative-Mother-SLCOG.pdf
http://emedicine.medscape.com/article/797150-overview#a0199
Royal College of Obstetricians and Gynaecologists (2011). Green-Top
Guideline No. 22: The Use of Anti-D Immunoglobulin for Rhesus D
Prophylaxis.
Roopnarinesingh (n.d.). Textbook of Obstetrics, 3 rd Edition
Hacker, Neville F., Gambone, Joseph C., Hobel, Calvin J. Essentials of
Obstetrics and Gynecology, Fifth Edition (2010)
http://
www.utilis.net/Morning%20Topics/Obstetrics/RH%20Isoimmunization.
pdf
http://www.nbts.gov.jm/pages.php?id=6

Aetiology
Non-Iatrogenic
Causes

At delivery (90%)
Stillbirths and
Intrauterine Deaths
Threatened Miscarriage
Spontaneous Abortion
(3.5%)

Induced Abortion (5.5%)

Ectopic Pregnancy
(~1%)
Antepartum
Haemorrhage
Abdominal Trauma (in
the third trimester)
Twin pregnancy (at
delivery)

Aetiology
Iatrogenic Causes
Maternal blood
transfusion
Amniocentesis
Chorionic Villus
Sampling
Cordocentesis/
Percutaneous
Umbilical Blood
Sampling

External Cephalic
Version
Dilation and Curettage
(to remove POC)
Caesarean Section
Active Management of
the 3rd stage of labour