Hemophilia is an inherited (genetic) disorder that prevents blood from clotting properly. Blood clotting is one of the basic requirements for life. It involves two different and extraordinarily complex set of factors. One factor requires specialized blood cells made in the bone marrow, called platelets. These small white cells play a central role in enabling the blood to clot. The other set of factors includes the coagulation system, which consists of a coordinated series of chemical reactions that are initiated when there is damage to tissue that can disrupt the blood vessels. This leads to bleeding and to the start of the process that can clot and stop the bleeding.

Deficiencies of the clotting process lead to excessive bleeding in people with hemophelia, even when trivial types of trauma occur. In general, clotting means the blood thickens or congeals to form a scab, which keeps a cut from bleeding endlessly. People with hemophilia bleed longer than usual. This bleeding can range from mild to severe. In severe cases, people with hemophilia can bleed to death.

There are approximately 13 clotting factors involved in blood coagulation. These factors are named according to when they become active in the coagulation process. When one clotting factor has been activated (i.e., called to participate in coagulation) it is given the additional letter "a" after the factor. So when Factor X becomes active, it is called Factor Xa. The main and most important clotting factors involved in hemophelia are Factor VIII, Factor IX and Factor XI.

People with hemophilia do not have enough clotting factors. This is caused by a defect in DNA. DNA is the genetic code you inherit from your parents. It defines your eye color, height and much more.

In the United States, about 17,000 people have hemophilia. It is almost exclusively a male disease. Females can get it, but it is very rare. Why is this a "male" disorder? Here's a quick lesson in genetics:

All people have 23 pairs of chromosomes, which are coiled pieces of DNA. Women have two X chromosomes. Men have one X chromosome and one Y chromosome. Hemophilia is caused by defects in X chromosomes. If a woman has a defect on one X chromosome, she can fall back on her other (unaffected) X chromosome and not develop hemophilia. (A person needs both X chromosomes to be abnormal.) Because a man has only one X chromosome, if he has a defect on it, he has no other X chromosome to rely on.

Women with one defective X chromosome and one normal X chromosome are carriers of hemophilia. In the very rare cases in which a woman gets hemophilia, it's because she inherited two defective X chromosomes, one from her mother (a carrier) and one from her father (who has hemophilia).

In most cases, the defective gene that leads to hemophilia is passed down through several generations, but in about 20% of cases, the defect arises as a spontaneous mutation (a new DNA defect) in the parent or affected child.

Hemophilia A and B are the two most common types of hemophilia.

• Hemophilia A is the most common type of hemophilia, occurring in about 80% of people with the disorder. People with hemophilia A do not have enough clotting factor VIII, which is caused by a DNA defect on the X chromosome that produces deficiencies in factor VIII.
  
  The extent of the bleeding problem relates to the amount of clotting factor the person has. People with levels less than 1% of the normal amount of clotting factor have severe disease. People with 1% to 5% of normal levels have moderate disease, and people with more than 5% of normal levels have mild disease. Two-thirds of people with hemophilia A have severe disease.



• Hemophilia B, also known as Christmas disease (named after the family in whom it was first diagnosed), accounts for 12% to 15% of hemophilia cases. Caused by a deficiency in clotting factor IX, hemophilia B is linked to an inherited problem on the X chromosome. It can be mild, moderate or severe. People with hemophilia B are less likely to have severe disease than people with hemophilia A. About half of people with hemophilia B have mild or moderate disease.

Factor XI deficiency, also called hemophilia C, is another type of clotting disorder. Caused by a deficiency in clotting factor XI, it is not inherited on the X chromosome. This means that bleeding problems can be passed to both male and female children and either parent may be a carrier. A child who inherits the problem from only one parent usually has high enough levels of clotting factor XI to prevent significant bleeding. However, a child who inherits the problem from both parents may have only 1% to 10% of normal factor XI levels, which may cause significant bleeding.

People with hemophilia may bleed anywhere throughout the body, but they seldom bleed from small cuts or puncture wounds, such as from the needles used to draw blood. They bleed more than other people do from significant injuries, trauma or surgery. Eighty percent of the time, they bleed into joints (hemarthroses), usually the ankle, knee or elbow. The affected joint becomes warm, painful and swollen, and the person is not able to move the joint as freely as before. This can happen after an injury or without any cause.

Bleeding into muscle (hematomas); into the esophagus, stomach or intestine (gastrointestinal bleeds); into the urine (hematuria); and from the nose and gums, and, in women, heavy menstrual bleeding are also common. A less common, but more serious complication of severe hemophilia is bleeding into the brain. Symptoms include the sudden development of nausea, headache and decreased mental awareness.

How bad and how often people bleed directly relates to how much coagulation factor they have. People with severe hemophilia often develop bleeding problems within the first two years of life. Many infants are diagnosed when they have prolonged bleeding after circumcision. Others are diagnosed after they develop excessive bruising and bleeding into joints after typical childhood injuries. People with mild hemophilia may not be diagnosed for decades, and only after they experience abnormal bleeding after trauma, injury or surgery.

In general, symptoms of factor XI deficiency usually appear only in people who inherit two defective chromosomes (one from each parent). These symptoms can include prolonged and/or excessive bleeding after cuts, surgery or dental extractions; nosebleeds (epistaxis); blood in the urine (hematuria); and (in girls) abnormally heavy or prolonged menstrual bleeding. Unlike in hemophilia A and B, bleeding without any cause is rare.

If your doctor suspects that you have hemophilia, he or she will ask how often you bleed and how severely. Your doctor will also ask if anyone in your family has a bleeding problem. In most cases, the person's mother will have a family member with a bleeding problem. Your doctor will examine you, focusing on evidence of past bleeding into the skin, muscles and joints. A variety of blood tests will show if your blood has a clotting defect. If you have a clotting defect, the diagnosis of hemophilia A or B or factor XI deficiency can be confirmed by examining specific clotting factors.

Hemophilia is a lifelong illness. Symptoms usually can be controlled with proper medical treatment.

People with a family history of hemophilia can talk to a genetic counselor to learn their risks of passing hemophilia to their children. A simple blood test is usually all that is necessary.

People with hemophilia can help to prevent episodes of bleeding by avoiding injuries, accidents and excessive strain on the joints. An infant with hemophilia should have appropriate padding in his crib or playpen, and he should be supervised as he learns to walk. In school, he should avoid contact sports and physical education activities that have a high risk of trauma. Instead, encourage the child to participate in walking and swimming, although he should avoid the diving team.

You can decrease the risk of joint damage significantly through preventive treatment. This means using clotting factor concentrates, starting early in life. These products help to decrease how often and how severely you bleed. People with hemophilia must avoid aspirin and other medications that affect blood clotting.

Because people with hemophilia may need a blood transfusion at some point, you should be immunized against hepatitis A and B, diseases that can be carried in blood products.

In the past, people would receive concentrates of the clotting factors that had been collected from the blood of many donors. The transfusion of material sometimes spread deadly viruses such as hepatitis and the AIDS virus. At the time that AIDS was just beginning to be understood, many hemopheliacs contracted the HIV virus that later caused AIDS and death.

When the biotechnology industry began to understand how to clone portions of the DNA that controlled Factor VIII and Factor IX production, advances were made into understanding the structure of these complicated, large molecules. Eventually, biotechnology techniques, called recombinant DNA technology, led to the creation of vast quantities of Factor VIII and Factor IX (called recombinant Factor VIII and recombinant Factor IX). This eliminated the need for blood donors and the risk of transmitting viruses.

Hospital treatment is necessary when bleeding occurs. The situation is an emergency when it involves the brain, neck, any component of the central nervous system or any vital organ. All surgical or invasive procedures should be done in a hospital to properly handle bleeding. Consult your doctor before having dental work. While the use of the recombinant factors can certainly help avoid these situations, hemophiliacs can still develop complications associated with blood transfusions when these blood products are needed to treat excessive blood loss.

If you are a parent, call your doctor whenever you notice unexplained or severe bruises on your child's body, or a warm, painful joint. If you are an adult and you experience these symptoms, call your doctor. The testing of blood factors and the appropriate interpretation requires the skill of professionals trained in both hematology and blood coagulation disorders. It is strongly recommended that people with bleeding disorders consult with one of these specialists.

How well you do depends on the type of hemophilia and its severity. In the 1950s, 60% of males with severe hemophilia A did not live to become adults. Today, thanks to the development of clotting factor products, most people with hemophilia can look forward to a near-normal lifespan.

There are three main complications that may develop in people with hemophilia:

• Joint destruction � Many people with hemophilia develop severe joint damage from multiple episodes of bleeding into joints (hemarthroses).



• Blood-borne infection � In the 1970s and early 1980s, many people with hemophilia developed hepatitis C, and up to half developed HIV. However, with improved testing and purification techniques, it is now exceedingly rare for these infections to be transmitted through blood products.



• Development of inhibitor antibodies � About 25% of people with severe hemophilia A and up to 5% of people with severe hemophilia B who are treated with clotting factors will develop inhibitor antibodies. These are infection-fighting proteins that decrease the effectiveness of the clotting treatment. When this occurs, treatment can be complicated and expensive.

National Heart, Lung, and Blood Institute (NHLBI)
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Phone: 301-592-8573
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Email: nhlbiinfo@rover.nhlbi.nih.gov
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