Hemophilia type A

Hemophilia A is a genetic disorder caused by missing or defective Factor VIII protein. It is inherited, but
in about one-third of known cases it is caused by a spontaneous genetic mutation.

The blood disorder affects all ethnic groups equally. More than half of all people with hemophilia A have
a severe form of the disease.

Hemophilia A is carried by the X chromosome. It is inherited in an X-linked recessive manner. As such,

two hemophilia-carrying X chromosomes must be inherited for the disease to be active in women, but
only in one X chromosome for men.

A female inherits two XX chromosomes, one from her mother and one from her father (XX). A male
inherits an X chromosome and a Y chromosome from her father (XY). This means that if a son inherits an
X chromosome from his mother who carries hemophilia, he will have hemophilia. But because women
receive two X chromosomes, only if both parents carry the defective gene can they develop the disease.

Hemophilia A has three stages: mild, moderate and severe, depending on the ratio of Factor VIII clotting
protein in the blood. Mild hemophilia 6-49 percent, moderate hemophilia is 1-5 percent, and severe is
less than 1 percent.

People with hemophilia A bleed longer than others, internally or externally. Those with mild hemophilia
A generally bleed only after serious injury, trauma or surgery. Often, the disease is diagnosed after one
of these situations due to prolonged bleeding, and the first episode may occur only in adulthood.
Women often experience heavy menstrual periods and can hemorrhage after giving birth.

Moderate hemophilia patients tend to have more frequent bleeding episodes after less important
injuries, or even spontaneously. In severe cases, bleeding may occur spontaneously in the joints and
muscles.
Hemophilia A should be diagnosed and treated at a specialized hemophilia center. Tests that evaluate
clotting time and a patient’s ability to form a clot may be ordered. A clotting factor test, called an assay,
will determine the type of hemophilia and its severity.

The main treatment for hemophilia A is concentrated Factor VIII product, which is administered
intravenously.

Patients with severe hemophilia may be given a routine treatment regimen called prophylaxis to
maintain enough clotting factor in their bloodstream to prevent bleeds.

Hemophilia type B
Hemophilia B is a genetic disorder caused by missing or defective Factor IX clotting protein. It is also
inherited, and just like hemophilia A, it can be caused by a spontaneous genetic mutation in one-third of
the cases. This type of hemophilia also affects all ethnic groups equally, but it is about four times as rare
as hemophilia A.

Hemophilia B is also carried in the X chromosome, in an X-linked recessive manner, meaning that two
hemophilia-carrying X chromosomes must be inherited for the disease to be active in women, but only
in one X chromosome in men.

Females inherit two XX chromosomes, one from their mother and one from their father (XX). Males
inherit an X chromosome and a Y chromosome from their father (XY). This means that is a son inherits
an X chromosome from his mother that has carries hemophilia, he will have hemophilia. But because
women receive two X chromosomes, it’s only if the two carry the defective gene, that they develop the
disease.

Severity levels are the same as hemophilia A, as well as symptoms.

Like hemophilia A, hemophilia B should be diagnosed at a specialized medical facility. Tests that evaluate
clotting time and a patient’s ability to form a clot may be ordered. A clotting factor test, called an assay,
will determine the type of hemophilia and its severity.
In hemophilia B, the most common treatment is the administration of concentrated Factor IX,
administered intravenously. Severe cases of hemophilia B will also be on prophylaxis treatment, to
maintain Factor IX clotting factor.

Hemophilia type C
Hemophilia C is a genetic disorder caused by missing or defective Factor XI clotting protein. The disease
was first recognized in 1953 in patients who experienced severe bleeding after dental extractions.

The incidence of hemophilia C is estimated at one in every 100,000 people in the general population. In
Israel, Factor XI deficiency occurs in up to 8 percent of Ashkenazi Jews due to intermarriage. This is
because a Factor XI deficiency is inherited in an autosomal recessive pattern, meaning both parents
must carry the gene to pass it on to their children. Unlike hemophilia A and B, men and women are
affected equally.

Factor XI plays an important role in the clotting cascade, which leads to clotting. It helps generate more
thrombin, a protein that converts fibrinogen to fibrin, which traps platelets and helps hold a clot in
place.

Unlike hemophilia A and B, symptoms don’t correlate with Factor XI levels in the blood. People with
lower levels may bleed less than those with higher levels of Factor XI. Patients often experience
nosebleeds or soft tissue bleeds, as well as hemorrhaging after tooth extraction.

Many women may not know they’re deficient in Factor XI until they experience menorrhagia (heavy
menstrual periods) or postpartum bleeding. In hemophilia C, joint and muscle bleeds are uncommon.

To diagnose hemophilia C, doctors will order a bleeding time test, platelet function tests, and
prothrombin time (PT) and activated partial thromboplastin time (aPTT) tests.
Factor XI concentrates are unavailable in the United States as yet, so doctors normally treat hemophilia
C with fresh frozen plasma. But because Factor XI is not concentrated in this treatment, large amounts
may be necessary, which can lead to blood clots. This treatment must be administered carefully.