Haemophilia A and B
Haemophilia A and B are disorders of blood clotting
caused by mutations in one of two closely linked genes on the X
Haemophilia A and B are two diseases characterised by slow and
inefficient formation of blood clots leading to prolonged bleeding
from minor wounds and spontaneous internal haemorrhage. The
diseases are caused by mutations in two closely linked genes on the
Haemophilia A and B are single gene disorders caused by
malfunctioning genes on the X chromosome. They are both recessive
diseases, and therefore occur much more commonly in males than
females. This is because two defective chromosomes must be present
for the disease to occur in females, whereas only one is required
in males. Haemophilia A is the commoner of the two diseases,
affecting one in 5000 males, whereas haemophilia B affects
approximately one in 40 000 males.
Haemophilia A is one of the better-known inherited disorders
because Queen Victoria was a carrier and transmitted the disease to
several European royal families.
The disease genes, known as F8 and F9 are found close together
on the long arm of the X chromosome. They encode proteins known
respectively as factor VIII and factor IX, which play key roles in
the blood coagulation cascade. In response to trauma or injury,
these proteins are needed to activate another component of the
cascade, factor X. It is factor X that converts the inert
circulating protein prothrombin into active thrombin, which in turn
converts fibrinogen into fibrin, the protein that forms the
substance of blood clots.
Haemophilia A and B have very similar symptoms, and both can
range from mild to severe depending on how little of each protein
is produced. Mild forms of the diseases, in which there is only a
moderate reduction in factor VIII or factor IX, result in longer
than normal healing times for minor wounds caused by trauma or
In the most severe cases, where factor VIII or IX are reduced to
below 1 per cent of their normal levels, there is a significant
delay in clotting resulting in protracted bleeding, and there may
be spontaneous haemorrhaging into joints in muscles, resulting in
swelling and pain and eventual deformation of joints.
The severe forms of the disease are diagnosed by the easily
recognisable symptoms - bleeding, haemorrhaging and bruising.
The two different forms of the disease can be distinguished by a
process of elimination (seeing whether the administration of factor
VIII or factor IX helps alleviate the symptoms) and by direct
testing of DNA for the presence of mutations in the F8 and F9
For many years, haemophilia has been treated successfully by the
regular injection of purified factor VIII or factor IX into the
blood. To avoid risks of contamination with viruses and prions,
recombinant factor VIII produced in bacteria can be used instead.
In each case, the injected protein lasts only a few hours, so the
doses must be maintained especially under circumstances where
bleeding is likely (e.g. surgery).
Haemophilia gene therapy is also being investigated because only
small amounts of each factor are required in the blood to alleviate
the disease symptoms.