Hemophilia A is a rare genetic disorder caused by missing or defective factor VIII (FVIII), a clotting protein in the blood. The disease usually is inherited, but in about a third of the cases, it is caused by a spontaneous mutation. More than half of all patients eventually develop a severe form of the disease.
The disease occurs in more than 400,000 males worldwide, many of whom are still undiagnosed. In the U.S., hemophilia A affects one in about 5,000 male births, and about 400 babies are born with the disease each year. This type of hemophilia accounts for 80% of all disease cases.
Genetics and inheritance
Hemophilia A is caused by changes (mutations) in the F8 gene that is on the X chromosome — one of two sex-determining chromosomes in humans. As such, the disease is inherited in an X-linked pattern.
Females inherit two X chromosomes — one from their mother and one from their father. Males inherit an X chromosome from their mother and a Y chromosome from their father. This means that if a man has inherited an X chromosome from his mother that contains an F8 gene mutation, he will develop hemophilia.
For women, the situation is slightly more complex because they have two X chromosomes. During development, one of the two X chromosomes is inactivated randomly to prevent multiple gene copies from being active at the same time. If a woman inherits a single faulty copy of the F8 gene, but the healthy copy is inactivated in most cells during development, she also may develop hemophilia. If, by contrast, the chromosome containing the F8 gene mutation is inactivated in most cells during development, she most likely will not develop hemophilia, but will be a carrier of the disease and risk passing the faulty gene to her children.
Since females are unlikely to have two mutated copies of the F8 gene, hemophilia A is more common in males.
Symptoms of hemophilia A depend on the amount of FVIII the body can produce. In severe hemophilia A, patients experience excessive spontaneous bleeds that have no apparent cause. Bleeds may occur inside the body, including in the mouth, joints, and muscles. Bleeding also may occur outside the body, from small cuts or injuries.
People with milder forms of hemophilia A usually do not have spontaneous bleeds. Rather, they may have significant bleeding after a severe injury or surgery. Therefore, in these patients hemophilia may remain undiagnosed until adulthood, unlike those with more severe forms of the disease that are often identified earlier in life.
While no cure exists for hemophilia A, the disease can be managed in different ways.
Replacement therapy, a form of treatment that involves providing the missing FVIII to patients, is one of the standard treatments for hemophilia A.
Replacement therapy can be used as an on-demand treatment on specific occasions to treat an acute bleed or on a routine basis to prevent bleeding episodes from occurring. This later form of treatment, known as prophylaxis, often is recommended to patients with more severe forms of hemophilia A.
Some patients with milder forms of the disease may be treated with desmopressin, which raises the levels of all clotting factors in the blood. Antifibrinolytics, which slow the breakdown of blood clots, also may be used to treat milder forms of the disorder.
Last updated: Nov. 23, 2021
Hemophilia News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.