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Hemophilia A
(Factor
VIII Deficiency)
What Is It?
Hemophilia is a bleeding disorder caused by
a deficiency in one of the blood clotting factors. Hemophilia A (often called
classic hemophilia) accounts for about 80 percent of all hemophilia cases. It is
a deficiency in clotting factor VIII.
Hemophilia A is a hereditary disorder in which the clotting ability of the blood
is impaired and excessive 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.
Severity of symptoms can vary, and severe forms become apparent early on.
Prolonged bleeding is the hallmark of hemophilia A and typically occurs 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 there is excessive bleeding and clotting problems in response to surgery or
trauma. Internal bleeding may happen anywhere, and bleeding into joints is
common.
The incidence of hemophilia A is 1 out of 10,000 live male births. About 17,000
Americans have hemophilia. Women may have it, but it's very rare. With treatment
and management, the outcome is good. Most men with hemophilia are able to lead
relatively normal lives.
Inheritance Pattern
Hemophilia A 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 have the disease and 50%
of their female offspring are carriers. All female children of a male with
hemophilia are carriers of the trait.
One third of all cases of hemophilia A 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
The only way a woman could ever have hemophilia is if her father has it and her
mother carries the gene. Women who are carriers can also be symptomatic
carriers, whereby they do experience factor deficiencies.
Symptoms & Diagnosis
Hemophilia is caused by several different gene abnormalities. The severity of
the symptoms of hemophilia A depends on how a particular gene abnormality
affects the activity of factor VIII. When the activity is less than 1 percent of
normal, episodes of severe bleeding occur and recur for no apparent reason.
Symptoms include:
• 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
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 have prolonged bleeding 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).
Recurring 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
A and can determine the severity by testing the activity of factor VIII.
Treatments
Hemophilia is 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. In the past, mild hemophilia A was typically treated with
infusion of cryoprecipitate or desmopressin acetate (DDAVP), which causes
release of factor VIII that is stored within the body on the lining of blood
vessels. Today, experts recommend desmopressin injection or Stimate nasal spray.
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 day, 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.
To prevent a bleeding crisis, people with hemophilia and their families can be
taught to administer factor VIII concentrates at home at the first signs of
bleeding. People with severe forms of the disease may need regular prophylactic
infusions, which bring factor levels higher than 1% to prevent bleeds.
Depending on the severity of the disease, DDAVP or factor VIII concentrate may
be given prior to dental extractions and surgery to prevent bleeding.
Immunization with hepatitis B vaccine is necessary because of the increased risk
of exposure to hepatitis due to frequent infusions of blood products.
Gene therapy and fetal tissue implant techniques are under study as possible
treatments.
People who have hemophilia should avoid situations that might cause bleeding.
They should be conscientious about dental care so they won't need to have teeth
extracted. 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
Treatment should be coordinated by a healthcare practitioner who is expert in
the field, such as a hematologist of hemophilia treatment center nurse.
The National Hemophilia Foundation's Medical and Scientific Advisory Council (MASAC)
made recommendations for treatment of hemophilia in November of 1999. They
include:
• Factor VIII products for patients who are HIV seronegative, including
Recombinant factor VIII, especially for young and newly diagnosed patients who
have not received any blood or plasma-derived products.
• Immunoaffinity purified factor VIII concentrates for patients who are HIV
seropositive.
• Cryoprecipitate is not recommended because of the risk of HIV and hepatitis
infection. Despite greatly improved screening and purification for viral
inactivation in blood products, cryoprecipitate can still contain viruses.
• Mild hemophilia A should be treated with desmopressin, in a DDAVP injection or
Stimate nasal spray.
Complications
• Chronic joint deformities, caused by recurrent bleeding into the joint, may be
managed by an orthopedic specialist.
• Intracerebral hemorrhage is another possible complication.
Some persons with hemophilia develop antibodies to transfused factor VIII. As a
result, the transfusions are 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 and a genetically engineered factor VIII (Recombinant).
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