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What Is It?
Hemophilia is a bleeding disorder caused by a deficiency in one of the
blood clotting factors. Hemophilia B (also called "Christmas disease" after
Stephen Christmas, a 20th-century British boy who was first diagnosed with
it) is a deficiency in clotting factor IX.
Hemophilia A is 7 times more common than hemophilia B. The incidence of
hemophilia B is 1 out of 34,500 men.
Hemophilia B is a hereditary disorder in which the clotting ability of the
blood is impaired and prolonged bleeding results. Small wounds and punctures
are usually not a problem. But uncontrolled internal bleeding can result in
pain and swelling and permanent damage, especially to joints and muscles.
The outcome is good with treatment and management. Most people with
Hemophilia B are able to lead relatively normal lives.
Inheritance Pattern
Hemophilia B is caused by an inherited sex-linked recessive trait with the
defective gene located on the X chromosome. Females are carriers of this
trait. Fifty percent of the male offspring of female carriers will have the
disease, and 50% of their female offspring will be carriers. All female
children of a male with hemophilia will be carriers of the trait.
One fifth of all cases of hemophilia B occur when there is no family history
of the disorder. In these cases, hemophilia develops as the result of a new
or spontaneous gene mutation.
Genetic counseling may be advised for carriers. Female carriers can be
identified by testing.
A woman is definitely a hemophilia carrier if she is:
• The biological daughter of a man with hemophilia
• The biological mother of more than one son with hemophilia
• The biological mother of one hemophilic son and has at least one other
blood relative with hemophilia
A woman may or may not be a hemophilia carrier if she is:
• The biological mother of one son with hemophilia
• The sister of a male with hemophilia
• An aunt, cousin, or niece of an affected male related through maternal
ties
• The biological grandmother of one grandson with hemophilia
Symptoms & Diagnosis
Hemophilia is caused by several different gene abnormalities. Severity of
Hemophilia B symptoms depends on how a particular gene abnormality affects
the activity of factor IX. When the activity is less than 1 percent of
normal, episodes of prolonged bleeding may occur for no apparent reason.
Severity of symptoms can vary, but severe forms become apparent early on.
Prolonged bleeding is the disease's hallmark and typically manifests itself
when an infant is circumcised. Additional bleeding manifestations make their
appearance when the infant becomes mobile. Mild cases may go unnoticed until
later in life, when they occur in response to surgery or trauma. Internal
bleeding may occur anywhere and bleeding into joints is common.
Risk factors are a family history of bleeding and being male. The incidence
of hemophilia B is 1 out of 34,500 men.
Symptoms include:
• Nosebleeds
• Bruising
• Spontaneous bleeding
• Bleeding into joints and associated pain and swelling
• Gastrointestinal tract and urinary tract hemorrhage
• Blood in the urine or stool
• Prolonged bleeding from cuts, tooth extraction, and surgery
• Prolonged bleeding following circumcision
People whose clotting activity is 5 percent of normal may have only mild
hemophilia. They rarely have unprovoked bleeding episodes, but surgery or
injury may cause uncontrolled bleeding, which can be fatal. Milder
hemophilia may not be diagnosed at all, although some people whose clotting
activity is 10 to 25 percent of normal may bleed excessively after surgery,
dental extractions, or a major injury.
Generally, the first bleeding episode occurs before 18 months of age, often
after a minor injury. A child who has hemophilia bruises easily. Even an
injection into a muscle can cause bleeding that results in a large bruise (hematoma).
Continuous bleeding into the joints and muscles can ultimately lead to
crippling deformities. Bleeding can swell the base of the tongue until it
blocks the airway, making breathing difficult. A slight bump on the head can
trigger substantial bleeding in the skull, causing brain damage and death.
A doctor may suspect hemophilia in a child whose bleeding is unusual. A
laboratory analysis of blood samples can determine whether the child's
clotting is abnormally slow. If it is, the doctor can confirm the diagnosis
of hemophilia and can determine the severity by testing the activity of
factor IX.
Coagulation studies involving many tests are performed if the person tested
is the first one in the family to have the bleeding disorder. Once the
defect has been identified, other family members will need less testing to
diagnose the disorder.
Treatments
Like hemophilia A, hemophilia B is typically treated by infusing the missing
clotting factor. The amount infused depends upon the severity of bleeding,
the site of the bleeding, and the size of the patient. Hepatitis B vaccine
is recommended for individuals with hemophilia B because they are at
increased risk of developing hepatitis due to exposure to blood products.
Clotting factors are found in plasma and, to a greater extent, in
plasma concentrates. Some plasma concentrates are intended for home use and
can be self-administered, either on a regular basis to prevent bleeding or
at the first sign of bleeding. More often, they are administered three times
a week (prophylaxis), but both the dose and frequency depend on the severity
of the bleeding problem. The dose is adjusted according to the results of
periodic blood tests. During a bleeding episode, more clotting factors are
needed. Treatment should be coordinated by a health care practitioner who is
expert in the disease.
To prevent a bleeding crisis, people with hemophilia and their families can
be taught to administer factor IX concentrates at home at the first signs of
bleeding. People with severe forms of the disease may need regular
prophylaxis infusions two to three time a week. Depending on the severity of
the disease, factor IX concentrate may be given prior to dental extractions
and surgery to prevent bleeding.
Gene therapy and fetal tissue implant techniques are under study as possible
treatments.
People who have hemophilia should avoid situations that might provoke
bleeding. They should be conscientious about dental care so they won't need
to have teeth extracted. If people who have milder forms of hemophilia need
to have dental or other surgery, the drug desmopressin acetate (DDAVP may be
given to improve clotting temporarily so that transfusions can be avoided.
People who have hemophilia should also avoid certain drugs that can
aggravate bleeding problems:
• Aspirin
• Heparin
• Warfarin
• Certain analgesics such as nonsteroidal anti-inflammatory drugs
The National Hemophilia Foundation's Medical and Scientific Advisory Council
(MASAC) made recommendations for treatment of hemophilia B in November of
1999. They include:
• Recombinant factor IX products for patients who are HIV seronegative,
especially for young and newly diagnosed patients who have not received any
blood or plasma-derived products.
• Today, plasma-derived factor IX products offer greatly reduced risk for
HIV and hepatitis B and C transmission, but there is still some risk. Dry
heating, solvent-detergent treatment, vapor treatment, and sodium
thiocyanate plus ultrafiltration and are all effective purification steps
but there remains a slight possibility of viral transmission.
• Patients who are HIV seropositive should also be treated with high purity
products such as immunoaffinity purified and recombinant factor VIII
products.
• For patients with inhibitors to factors VIII and IX, there is Recombinant
Factor VIIa (NovoSeven). Produced by baby hamster kidney cells, no human
albumin or other proteins are used in its production, reducing virus risk.
There is also Porcine factor VIII (Hyate C), and activated prothrombin
complex concentrates.
Complications
• Chronic joint deformities, caused by recurrent bleeding into the joint,
may be managed by an orthopedic specialist.
• Intracerebral hemorrhage may also occur.
• Thrombosis may occur following use of factor IX concentrate.
Some persons with hemophilia develop antibodies to transfused factor IX. As
a result, transfusions become ineffective. If antibodies are detected in
blood samples, the dosage of the plasma concentrates may be increased, or
different types of clotting factors or drugs to reduce the antibody levels
may be used.
In the past, the plasma concentrates carried the risk of transmitting
blood-borne diseases such as hepatitis and AIDS. About 60 percent of persons
with hemophilia who were treated with plasma concentrates in the early 1980s
were infected with HIV. However, the risk of transmitting HIV infection
through plasma concentrates has been virtually eliminated by today's use of
screened and processed blood. |
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