Rhesus Disease
Rhesus Disease is a maternal, anti-Rhesus factor antibody induced, hemolytic response in the fetus and
neonate.
Epidemiology
Prior to the availability and wide use of immunoprophylaxis, Rhesus disease had an incidence of 1% and
killed one neonate in every 2200 births. 16% of Caucasian mothers are Rhesus negative and the
identification of these women is fundamental to the prevention of Rhesus disease.* Genotyping of both
parents to assess fetal risk

Non-invasive fetal genotyping using maternal plasma

Amniocentesis to assess fetal anemia - fetal bilirubin is excreted into the amniotic fluid

Doppler ultrasound scans can also assess anemia

Checking maternal antibodies
Etiology
Rhesus disease is always caused by maternal antibodies crossing the placenta into the fetal circulation and
mounting an immune response against the fetal red blood cells. These antibodies recognize and attack red
blood cells expressing the antigen protein rhesus factor. For this to happen, the mother must be Rhesusnegative and the fetus must be Rhesus positive. Also, the mother must have had previous exposure to the
Rhesus factor antigen. This can happen in two ways:

A previous pregnancy with a Rhesus-positive child whose red blood cells crossed the placenta into the
mother's circulation

A previous blood transfusion with Rhesus-positive blood
The former cause of isoimmunisation of the mother is the most common. A newly-sensitized mother will
now remain sensitized for life. Therefore, any subsequent exposure to Rhesus-positive blood will result in
an immune response against the Rhesus factor antigen.
The genetics of this condition begins with the genetics of the parents. The gene that codes for the Rhesus
factor antigen on the surface of red blood cells is autosomal dominant. So a woman who is genotypically
DD or Dd will be phenotypically Rhesus-positive and she will express Rhesus factor on the surface of her
red cells. Alternatively, if she is genotypically dd, she will be phenotypically Rhesus-negative, and will not
express the Rhesus factor antigen.
From this we can see that if a fetus is to be Rhesus positive, the father must be Rhesus positive too. He
may be of the heterozygous genotype, Dd, or the homozygous type DD. So, if a woman who is dd,
conceives a child with a man who is Dd, then there is a 50% chance that the child will be Dd and a 50%
chance the child will be dd. Alternatively, if a woman who is dd, conceives a child with a man who is DD,
then there is a 100% chance that the child will be Dd.
Therefore, for Rhesus disease to be possible, the following genetic criteria must be met:

The mother must be Rhesus negative (dd) and have had previous exposure to the Rhesus factor
antigen

The father must be Rhesus positive for Rhesus factor (Dd/DD)

The child must be Rhesus positive (Dd is the only genotype possible)
The newly-sensitized mother will now remain sensitized for life. Therefore, any subsequent exposure to
Rhesus-positive blood will result in an immune response against the Rhesus factor antigen. In a pregnancy
with an immunosensitised Rhesus-negative mother and a Rhesus-positive fetus, the anitbodies against
Rhesus factor will cross the placenta from the maternal circulation to the fetal circulation. This is Rhesus
disease, and has many complications.
Pathogenesis
Maternal antibodies in the fetal circulation target, attack and damage the fetal red blood cells. The affected
red cells travel in the circulation until they are cleared by the reticuloendothelial system of the fetus. The
liver works hard to metabolize the products of hemolysis and increases in size. There is an increase in
circulatory bilirubin which is excreted by the kidneys into the amniotic fluid. Fetal anemia results. In severe
cases the fetus may suffer from:

cardiac failure

oedema

hydrops fetalis
Prevention
The evidence of Rhesus disease can be assessed by:

Genotyping both parents to assess fetal risk

Non-invasive fetal genotyping using maternal plasma

Amniocentesis to assess fetal anemia - fetal bilirubin is excreted into the amniotic fluid

Doppler ultrasound scans can also assess anemia

Checking maternal antibodies
Anti-D can be given pre-delivery in those at risk to clear the fetal red cells before the mother has any
chance to mount an immune response. This preventative measure has revolutionized the obstetric
mangement of rhesus disease and saved the lives of numerous neonates.
Clinical Features
Clinical features include:

anemia

jaundice

hydrops fetalis

gross edema

hepatosplenomegaly

death
References

www.gpnotebook.co.uk

Kumar S, Regan F. Management of pregnancies with RhD alloimmunisation. BMJ 2005;330:1255-1258

O'Connor, J. Pathology 2nd ed. Mosby. Edinburgh. 2002.

McCarthy, A & Hunter, B (2003) Master Medicine: Obstetrics and Gynaecology (2nd ed.) Philadelphia:
Elsevier Saunder