Transcript Hemophilia presentation

Hemophilia
in
Canis familiaris
(dogs)
General information


MIM number: 306900
MIA number: 000438
What is hemophilia?



Hemophilia is a bleeding disorder of
varying severity that is due to a deficiency
in specific clotting factors.
It is an X-linked, recessive disorder which
is one of the few sex-linked traits in dogs.
Hemophilia found in dogs are very closely
related to the hemophilia found in
humans.
Sex
chromosomes
Chromosomes present in a
female dog

There are two major types of hemophilia:
Hemophilia A is defective in coagulation factor
VIII and is sometimes called royal hemophilia
because it occurred in descendants of Queen
Victoria.
 Hemophilia B is defective in coagulation factor
IX and is also known as Christmas disease
because it was first observed in a patient
named Stephen Christmas.


Both hemophilia types are X-linked
disorders but however differentiated
because it occurs on different genes on
the X chromosome.
History
Queen Victoria
Molecular Genetics of hemophilia


The molecular basis of hemophilia B are
mutations in the F9 gene.
This genetic disorder is caused by many
different types of mutations such as:
Deletions
 Insertions
 Point mutations
 Duplications
 Inversions




Because males have only 1 X
chromosome, a male dog is either affected
or clear of the defect.
Females, with 2 X chromosomes, may be
affected (abnormal gene on both
chromosomes), clear, or a carrier with no
clinical signs (one gene affected).
In effect, the disease is carried by
females but affects mostly males.
Factor IX
F9 gene





Cytogenetic Location: Xq27.1q27.2
The factor IX gene is about
34kb long.
Encompasses 8 exons and 7
introns.
Encodes a protein that
consists of 415 amino acids
And has a molecular weight of
57 000D
How does hemophilia work?
Clotting Cascade
Factor XII
Types of dogs affected
Bull Terrier
Lhasa Apso
Airedale Terrier
Labrador
Clinical signs of hemophilia B
Symptoms vary widely, based on the
severity of the bleeding disorder
 bloody diarrhea
 bleeding under the skin
 lameness
Clinical signs of hemophilia B
Where hemophilia is more severe, you may
see signs of a problem at a fairly early age
 Pups may have prolonged bleeding associated
with the loss of baby teeth.
 Bleeding under the skin
 Bleeding into muscles or joints will often cause
lameness.
 Unfortunately, dogs with severe hemophilia
often die or are euthanized because of recurrent
or uncontrollable bleeding problems.
Detection of hemophilia

Diagnosis is made through blood tests to
determine:
Blood clotting
 Level of clotting factors
 Missing clotting factors

How is hemophilia treated?
There is no cure for this disorder.


Periodic transfusions
Administer fresh plasma, fresh frozen
plasma, or cryosupernatant (factor IX)
plasma.
Gene Therapy