Factor 8 deficiency
Factor VIII deficiency
Hemophilia A, congenital
Hemophilia A is a bleeding disorder in which the blood does not clot normally. People with this disorder have prolonged bleeding or oozing after an injury, surgery, or tooth extraction. In severe cases, heavy bleeding occurs after minor injury or even when there is no injury (spontaneous bleeding). Serious complications can result from bleeding into the joints, muscles, brain, or other internal organs. In milder forms there is no spontaneous bleeding, and the disorder may not become apparent until after a surgery or serious injury.
The major types of this condition are hemophilia A (also known as classic hemophilia or factor VIII deficiency) and hemophilia B (also known as Christmas disease or factor IX deficiency). Although the two types have very similar signs and symptoms, they are caused by mutations in different genes.
The severity of symptoms vary. Bleeding is the main symptom of the disease. It is often first seen when an infant is circumcised. Other bleeding problems are seen when the infant starts crawling and walking.
Mild cases may go unnoticed until later in life. Symptoms may first occur after surgery or injury. Internal bleeding may occur anywhere.
Symptoms can include:
- Bleeding into joints, with associated pain and swelling
- Blood in the urine or stool
- Gastrointestinal tract and urinary tract hemorrhage
- Prolonged bleeding from cuts, tooth extraction, and surgery
- Spontaneous bleeding
Hemophilia A is inherited in an X-linked recessive manner and is caused by changes (mutations) in the F8 gene and with the defective gene located on the X chromosome. Females have two copies of the X chromosome. So if the factor VIII gene on one chromosome does not work, the gene on the other chromosome can do the job of making enough factor VIII.
Males have only one X chromosome. If the factor VIII gene is missing on a boy's X chromosome, he will have hemophilia A. For this reason, most people with hemophilia A are male.
If a woman has a defective factor VIII gene, she is considered a carrier. This means the defective gene can be passed down to her children. Boys born to such women have a 50% chance of having hemophilia A. Their daughters have a 50% chance of being a carrier. When a father has hemophilia A, none of his sons will inherit the condition, but all of his daughters will be carriers.
Risk factors for hemophilia A include:
- Family history of bleeding
- Being male
- Genetic counseling
- Prenatal intrauterine diagnosis with termination of pregnancy as an option
For a female carrier, there are four possible outcomes for each pregnancy:
- A girl who is not a carrier
- A girl who is a carrier
- A boy without hemophilia
- A boy with hemophilia
If you are the first person in the family to have a suspected bleeding disorder, your doctor will order a series of tests called a coagulation study. Once the specific defect has been identified, other people in your family will need to be tested to diagnose the disorder.
Tests to diagnose hemophilia A include:
- Serum factor VIII activity
- Prothrombin time
- Bleeding time
- Fibrinogen level
- Partial thromboplastin time (PTT)
With treatment, the outcome is good. Most people with hemophilia A are able to lead relatively normal lives. A small percentage of people with hemophilia A will develop inhibitors of factor VIII, and may die from loss of blood. People with hemophilia A should establish regular care with a hematologist (blood doctor), especially one is associated with a hemophilia treatment center. The ability to have quick and easy access to medical records documenting the level of factor VIII that the person has had, the history of factor transfusions (including the types and amounts), any complications, and the type and amount of any inhibitors can be lifesaving in the event the person with hemophilia is in an emergency situation.
Hemophilia can be mild, moderate, or severe, depending on how much clotting factor is in an affected person's blood. However, about 70% of patients have the severe form of the disorder.
With appropriate education and treatment, people with hemophilia can live full and productive lives. Prophylaxis (preventive measures) and early treatment have dramatically improved the long-term outlook (prognosis) for people with severe hemophilia. Replacement therapy has significantly improved life expectancy, and the availability of therapy at home has improved quality of life. About 25% of people with severe disease between 6-18 years of age do have below-normal motor skills and academic performance, and have more emotional and behavioral problems than others.
The most important life-threatening complications of hemophilia are intracranial hemorrhage (bleeding within the skull) and hemorrhages into the soft tissue around vital areas (such as the airway or internal organs). The lifetime risk of intracranial bleeding in affected people is 2-8% and accounts for one third of deaths due to hemorrhage. About 10% of those with severe hemophilia have intracranial bleeding, with a mortality rate of 30%. Chronic, debilitating joint disease can also develop.
Overall, the mortality rate for affected people is about twice that of the healthy male population. For severe hemophilia, the rate is about 4-6 times higher. In some cases the mortality rate depends on whether any other underlying diseases or conditions are present.
People with inherited hemophilia A require life-long care, preferably through a specialized hemophilia treatment center. Although there is no cure for hemophilia A, current treatments usually work well. Treatment primarily consists of replacing the missing clotting factor VIII (replacement therapy) and preventing complications that are associated with the disorder. The type and frequency of treatment often depends on the severity of the disorder in each person. The U.S. Food and Drug Administration (FDA) has approved ADYNOVATE [Antihemophilic Factor (Recombinant), PEGylated], an extended circulating half-life recombinant Factor VIII (rFVIII) treatment for hemophilia A, in pediatric patients under 12 years of age. The FDA also approved ADYNOVATE for use in surgical settings for both adult and pediatric patients.
People with mild or moderate hemophilia A may be treated with replacement therapy as needed (for example, when a specific bleeding episode occurs). This is called episodic 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 taken intravenously 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 those with a mild form of the disorder.