F8

About F8

F8 on chromosome Xq28 encodes coagulation factor VIII, a cofactor for factor IXa in the intrinsic tenase complex that activates factor X. Pathogenic variants cause hemophilia A, the most common severe inherited bleeding disorder, inherited in an X linked recessive pattern and therefore affecting mainly males. Severity is classified by residual factor VIII activity as severe, moderate, or mild. Severe disease causes spontaneous bleeding into joints, called hemarthrosis, and muscles, while milder forms cause bleeding mainly after injury or surgery. An inversion involving intron 22 accounts for nearly half of severe cases. Hemophilia was known as the royal disease because it spread through descendants of Queen Victoria. Treatment historically relied on factor concentrates made from pooled plasma, and many people with hemophilia were infected with HIV and hepatitis C through contaminated products in the 1980s. Recombinant factor VIII avoids this risk. Emicizumab, a bispecific antibody that bridges factor IXa and factor X to mimic factor VIII, is used for prophylaxis. Gene therapy with valoctocogene roxaparvovec delivers a functional F8 gene using an AAV5 vector.