Hemophilia A

Hemophilia A is caused by genetic changes (mutations) in the F8 gene. This gene is responsible for making the Factor VIII protein, an important protein that helps start the formation of blood clots. Mutations in the F8 gene lead to reduced or absent levels of Factor VIII in the blood, making it hard for the body to form blood clots.

The diagnosis of hemophilia A is made through the clinical symptoms and confirmed by laboratory testing. Blood tests are done to measure the time it takes the blood to clot and the amount of clotting factors found in the blood. Genetic testing can also help determine the exact change in the F8 gene and can be helpful for identifying other family members at risk for hemophilia A.

The F8 gene is located on the X-chromosome. Therefore, hemophilia A is inherited in an X-linked recessive pattern. In males (who have only one X chromosome), one mutated copy of the F8 gene in each cell is enough to cause hemophilia A. In females (who have two X chromosomes), a mutation needs to occur in both copies of the F8 gene to cause the disorder. Because it is unlikely that females will have two mutated copies of this gene, hemophilia A, like other X-linked recessive disorders, affects males much more frequently than females. Females who have a mutation in one copy of the F8 gene are called carriers. Most carriers have no signs or symptoms, however about 10% of female carriers of hemophilia A will experience some abnormal bleeding.

A female who carries one F8 gene mutation has a 50% or 1 in 2 chance of having a son with hemophilia A. A male with hemophilia A cannot pass on the disorder to his sons, but all of his daughters will be carriers for hemophilia A.

When a male child is the first person in a family with hemophilia A, further testing may be needed to determine if the child inherited the disorder from his mother, or if the mutation occurred by chance for the first time in the child.

Yes. Approximately 10% of women who are carriers for hemophilia A are at risk for abnormal bleeding episodes. One study found that 5 out of 55 people with mild hemophilia A were female.

Globally, approximately one in 5,000 males is born with hemophilia A. Males of every ethnicity are equally affected. For example, one in 5,000 Hispanic males, one in 5,000 African-American males, and one in 5,000 Caucasian males in the United States have this disorder.

Hemophilia A affects one in 5000 individuals whereas hemophilia B affects one in 20,000.

There are three forms of hemophilia A: severe, moderate, and mild. Up to 70% of people with hemophilia A have the severe form, in which symptoms begin before age 1. Symptoms of the moderate form begin between the ages of 1 and 2 years; at least 15% of affected people have the moderate form. About 15% of individuals have the mild form, which begins at age 2 or older.

Hemophilia A can be mild, moderate, or severe, depending on how much clotting factor VIII is in a person's blood. About 50-60% of people with hemophilia A have the severe form of the disorder.

With education and treatment, people with hemophilia A can live healthy and active lives. Life expectancy may depend on the response to treatment and the presence of other health conditions. Life-threatening complications of hemophilia A include bleeding within the skull (intracranial hemorrhage) and bleeding into the soft tissue around important organs. Chronic, debilitating joint disease may also develop.

About 1/5000 -1/6000 people in the US are born with hemophilia A. This disorder affects males more than females, and occurs equally in all races and ethnic groups.

People with inherited hemophilia A require life-long care, preferably through a specialized hemophilia treatment center. These centers are located around the United States and can be found through the Centers for Disease Control and Prevention. The National Hemophilia Foundation has links to management and treatment guidelines.

There is no cure for hemophilia A, but current treatments can prevent many of the symptoms of hemophilia A. Treatment may include medications and replacing the missing clotting factor (replacement therapy). This type of replacement therapy is done by slowly injecting or dripping concentrated factor VIII into a vein (intravenous infusion). The type and frequency of treatment often depends on the severity of the disorder in each person.

People with mild or moderate hemophilia A may be treated with replacement therapy as needed (for example, when a bleeding episode occurs). This is called ‘on-demand’ therapy. Some people with mild hemophilia A may be treated with desmopressin (DDAVP). Desmopressin raises the levels of factor VIII in the blood and may be given directly into a vein or through a nasal spray. Drugs known as antifibrinolytics, which slow the breakdown of clotting factors in the blood, can also be used to treat a mild form of the disorder.

Some people with severe hemophilia A may receive regular factor VIII replacement therapy to prevent bleeding episodes and other complications such as joint damage. This is referred to as prophylactic or preventative therapy. These factor VIII infusions may be done as often as necessary depending on the severity. The immune system of some people with the severe form of hemophilia A may start to make antibodies (inhibitors) that prevent the replacement factor VIII from working. Treatment for these people includes larger doses of replacement factor VIII and/or medications that may help block the inhibitors.

Infusions of replacement Factor VIII can be given at home. This is especially important for people with severe disease because the infusion works the best within one hour of a bleeding episode. In general, prompt treatment is important because it reduces pain and damage to the joints, muscles, or other affected tissues or organs.