Hemophilia A is a bleeding disorder caused by pathogenic variants in the F8 gene resulting in deficient or dysfunctional clotting factor VIII.
Clinical severity is classified by residual factor VIII activity: severe (<1% activity) presents in infancy or early childhood with spontaneous joint and muscle bleeds and bleeding with minor trauma or procedures, moderate (1–5%) presents with bleeding after minor trauma, and mild (>5%–40%) may present with bleeding only after significant trauma or surgery. Diagnosis rests on prolonged activated partial thromboplastin time with low factor VIII activity and confirmation by F8 molecular genetic testing; management centers on prevention or on-demand replacement with factor VIII concentrates, use of non-factor therapies for selected patients, and comprehensive care to prevent and treat bleeding complications, including inhibitor surveillance and individualized obstetric management for affected females.
Hemophilia A is caused by pathogenic variants in the F8 gene that exhibit X-linked recessive inheritance. This means that one pathogenic variant is enough to cause the disease in both individuals assigned male at birth (who have one X chromosome and one Y chromosome) and individuals assigned female at birth (who have two X chromosomes) may experience symptoms depending on how many copies of the X chromosome that has the pathogenic variant are turned on in the cells.
Resources:
National Bleeding Disorders Foundation
Written October 2025
