Health A-Z

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Harvard Medical School

Hemophilia

What Is It?

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 hemophilia, 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 hemophilia 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.