Trait Document

Individuals with hemophilia bleed longer than individuals without hemophilia. Hemophilia A is characterized by a wide range of signs and symptoms. These can include but are not limited to bleeding into joints and muscles, spontaneous bleeding (bleeding for no apparent reason), bleeding after trauma or surgery, easy bruising, intracranial bleeding (i.e., bleeding around the skull), gastrointestinal bleeding, and hematuria (blood in the urine). The degree of bleeding often depends on the severity of hemophilia present in the individual. Individuals with hemophilia A can have a variety of complications resulting from their bleeding disorder. These complications include varying degrees of joint disease due to a history of bleeding into the joint. The degree of joint disease depends on a variety of factors including the number of bleeds into the joint, past treatment for bleeding, and age.

Hemophilia A is caused by a changes or mutations in a gene called F8. The F8 gene makes the clotting factor VIII protein. Clotting factors are proteins that control bleeding. Mutations in the F8 gene do not allow the factor VIII protein to work properly, and this leads to the bleeding problems seen in affected individuals. Hemophilia A can be also be diagnosed by a laboratory finding of a decreased factor VIII activity level in blood. The normal range of factor VIII is generally between 50 and 150%. Levels below 40% are consistent with hemophilia. The bleeding disorder is divided into three categories of severity: severe (<1% factor VIII), moderate (1-5% factor VIII), mild (6-35% factor VIII).

Hemophilia A is treated with intravenous (IV) replacement of the missing clotting factor. Thus, individuals with hemophilia A are given replacement of factor VIII protein. Some individuals with mild hemophilia A can also be treated with DDAVP (also called desmopressin), a hormone that stimulates the release of factor VIII, depending on the severity of the bleed. Individuals with hemophilia A are treated with regular IV infusion of the missing clotting factor or by an “on-demand” schedule meaning they are infused when they experience a bleed. Which regimen an individual is prescribed depends on multiple factors including severity of hemophilia, age, lifestyle, number of bleeds, etc. When possible, aspirin and aspirin-containing products should be avoided in individuals with hemophilia A.

Hemophilia A is inherited in an X-linked recessive pattern. This means that in females, both copies of the F8 gene (i.e., one on each X chromosome) must have a change or mutation, whereas in males, only one copy of the F8 gene must have a mutation to be affected. A female with a mutation in one copy of the F8 gene is said to be a “carrier” of Hemophilia A, and is typically not affected.

If a father is affected with hemophilia A, his daughters will be carriers of hemophilia A and his sons will be unaffected. If a mother is a carrier of hemophilia A, each daughter has a 1 in 2 chance (i.e., 50%) of being a carrier and each son has a 1 in 2 chance (i.e., 50%) of being affected with hemophilia A.

A variety of reproductive options are available to individuals with a family history of hemophilia including natural conception, egg/sperm donation, prenatal diagnosis, and preimplantation diagnosis. Additional information about these options can be discussed with a genetic counselor.

Unlike many X-linked recessive disorders, female carriers of hemophilia A can have symptoms related to having a decreased factor VIII level. For this reason it is important that females as well as males with a family history of hemophilia A have their clotting factor activity levels checked.