Hemophilia

Hemophilia is a bleeding disorder that slows the blood clotting process. People with this condition often experience prolonged bleeding or oozing following an injury, surgery, or having a tooth pulled. In severe cases of hemophilia, heavy bleeding occurs after minor trauma or even in the absence of injury (spontaneous bleeding). Serious complications can result from bleeding into the joints, muscles, brain, or other internal organs. Milder forms of hemophilia do not involve spontaneous bleeding, and the condition may only become apparent when abnormal bleeding occurs following surgery or a serious injury.

The major types of this condition are hemophilia A (also known as classic hemophilia) and hemophilia B (also known as Christmas disease). Although the two types have very similar signs and symptoms, they are caused by mutations in different genes. People with an unusual form of hemophilia B, known as hemophilia B Leyden, experience episodes of excessive bleeding in childhood, but have few bleeding problems after puberty. Another form of the disorder, acquired hemophilia, is not caused by inherited gene mutations. This rare condition is characterized by abnormal bleeding into the skin, muscles, or other soft tissues, usually beginning in adulthood.

The two major forms of hemophilia occur much more commonly in males than in females. Hemophilia A is the most common type of the condition; about 1 in 4,000 males worldwide are born with this disorder. Hemophilia B occurs in approximately 1 in 20,000 newborn males worldwide.

Mutations in the F8 and F9 genes cause hemophilia.

Changes in the F8 gene are responsible for hemophilia A, while mutations in the F9 gene cause hemophilia B. The F8 gene provides instructions for making a protein called coagulation factor VIII. A related protein, coagulation factor IX, is produced from the F9 gene. Coagulation factors are proteins that work together in the clotting process. After an injury, blood clots protect the body by sealing off damaged blood vessels and preventing further blood loss.

Mutations in the F8 or F9 gene lead to the production of an abnormal version of coagulation factor VIII or coagulation factor IX. The altered protein cannot participate effectively in the blood clotting process and, in some cases, the protein does not work at all. A shortage of either protein prevents clots from forming properly in response to injury. These problems with blood clotting lead to excessive bleeding that can be difficult to control. Some mutations almost completely eliminate the activity of coagulation factor VIII or coagulation factor IX, resulting in severe hemophilia. Other mutations reduce but do not eliminate the activity of one of these proteins, which usually causes mild or moderate hemophilia.

The other, rare form of this condition, acquired hemophilia, results when the body makes specialized proteins called autoantibodies that attack and disable coagulation factor VIII. The production of autoantibodies is sometimes associated with pregnancy, immune system disorders, cancer, or allergic reactions to certain drugs. In about half of cases, the cause of acquired hemophilia is unknown.

Read more about the F8 and F9 genes.

Hemophilia A and hemophilia B are inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

In X-linked recessive inheritance, a female with one altered copy of the gene in each cell is called a carrier. She can pass on the altered gene to her children, but usually does not experience signs and symptoms of the disorder. In about 10 percent of cases, however, females who carry one altered copy of the F8 or F9 gene will experience mild problems with bleeding.