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.
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.
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.
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:
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.
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).