Hemophilia A:

The Royal
Disease


Rojensa Cekrezi
Definition
Hemophilia- love of bleeding
Factor VIII deficiency
X linked recessive trait, predominantly affects
males; females are often carriers unless both
parents carry hemophilia gene.
Clinical history: joint hemorrhage with joint
deformities, oral bleeding, bleeding into soft
tissues

Disease Discovery
1
st
written description-2
nd
century during Babylonian era
2
nd
century AD the Jewish Rabbinical stated If she circumcised her first
child and he died, the second one also died, she must not circumcise her
third child.
1803 Dr. John Conrad Otto wrote about a hemorrhagic disposition
existing in certain families.

History Cont
The Royal
Disease

Queen Victoria, Queen of
England from 1837 1901 Carrier
Queen Victorias granddaughter
married the Tsar of Russia and her
only son had hemophilia too.
Mode of
Inheritance
Chromosome involved
Coagulation factors
Necessary to form blood
clotting- 13 proteins,
platelets, and fibrin
Hemophilia A is caused
by a deficiency of
clotting of Factor VIII;
therefore, a person with
hemophilia has low or
non-existent levels of
blood clotting protein
factor
Bleed longer than usually


Hemophilia A is an inherited
bleeding disorders that causes
abnormal or prolonged bleeding
and poor blood clotting
2/3 of the cases of hemophilia are
inherited, whereas the other 1/3
occurs with no family history and
are called spontaneous genetic
mutations and acquired.
This rare condition is characterized
by abnormal bleeding into the skin,
muscles, or other soft tissues,
usually beginning in adulthood


Cont
Father with Hemophilia
and Mother Carrier
Deficiency of blood
clotting
Hemophilia Genetics
Carrier Mother
Genetics

Father with
Hemophilia Genetics

Gene Mutation
Since the disease follows an X-linked recessive mode of inheritance- the
genes for both coagulation factors are located at the distal end of the
long arm of the human X-chromosome at Xq28.
Normal carriers - clotting factor level is 50 = haemostasis, however; the
application of clotting and immunological methods allow to detect only
about 80% of the carriers due to the random inactivation of one X-
chromosome in females.
Molecular diagnosis of this disease as well as a carrier and prenatal
diagnosis is possible since the FVIII gene where cloned and
characterized.
The gene that codes for the factor VIII protein is 186 kilobit long and has
26 exons which code for the factor VIII protein.

Molecular techniques
used for detection
Southern blot
showing the the
factor VIII gene. intron
22 inversion of