Hemophilia

Hemophilia is a group of inherited bleeding disorders caused by deficiency or dysfunction of specific clotting factors in the blood. The two main forms are Hemophilia A (also called classic hemophilia), caused by deficiency of coagulation factor VIII, and Hemophilia B (also called Christmas disease), caused by deficiency of coagulation factor IX. Both forms are X-linked recessive conditions, meaning they predominantly affect males, while females are typically carriers who may occasionally experience mild bleeding symptoms. The hallmark of hemophilia is a tendency toward prolonged and excessive bleeding, particularly into joints (hemarthrosis) and muscles. Repeated joint bleeds can lead to chronic joint damage known as hemophilic arthropathy, which is a major source of disability. Other manifestations include easy bruising, prolonged bleeding after surgery or dental procedures, gastrointestinal bleeding, hematuria, and in severe cases, spontaneous intracranial hemorrhage, which can be life-threatening. The severity of bleeding correlates with the residual level of the affected clotting factor: severe hemophilia (factor level <1%) is associated with spontaneous bleeding episodes, moderate hemophilia (1–5%) with bleeding after minor trauma, and mild hemophilia (5–40%) with bleeding mainly after significant trauma or surgery. The treatment landscape for hemophilia has evolved significantly. Standard treatment involves replacement therapy with intravenous infusions of the deficient clotting factor, either on-demand (to treat active bleeds) or prophylactically (to prevent bleeds). Both plasma-derived and recombinant factor concentrates are available, and extended half-life products have reduced the frequency of infusions. For Hemophilia A, emicizumab, a bispecific antibody that mimics the function of factor VIII, represents a major therapeutic advance and is administered subcutaneously. Gene therapy has recently been approved for both Hemophilia A (valoctocogene roxaparvovec) and Hemophilia B (etranacogene dezaparvovec), offering the potential for sustained factor production. A significant complication of treatment is the development of inhibitory antibodies (inhibitors) against the infused factor, which occurs in approximately 25–30% of severe Hemophilia A patients and 3–5% of Hemophilia B patients, requiring alternative bypassing therapies or immune tolerance induction.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Hemophilia