Hemophilia A is a genetic bleeding disorder caused by a deficiency in clotting factor VIII. Treatment focuses on managing bleeding episode symptoms with clotting factor replacement therapy, immunotherapies, and gene therapy.
Hemophilia A results from genetic variations to the F8 gene on a person’s X chromosome. The F8 gene directs the production of clotting factor VIII, one of many proteins involved in blood clotting during bleeding.
Without enough factor VIII, blood clotting becomes impaired. Clots may not form quickly enough or provide enough structural stability to support wound closure. Bleeding does not speed up in hemophilia A but can persist for longer.
While there is no cure for hemophilia A, various treatment approaches can help manage it. This article looks at the standard treatments used in hemophilia A as well as emerging and novel therapies.
The
Plasma-derived factor VIII goes through an extensive purification process to reduce the risk of transmitting infectious agents, but a small risk does remain.
Recombinant factor VIII is considered much safer. It does not contain components of human blood.
Factor VIII replacement therapy involves an intravenous infusion.
Depending on the severity of hemophilia A, a person may receive infusions as needed during a bleeding episode, known as on-demand treatment, or on a regular schedule proactively, known as prophylaxis therapy.
On-demand treatment may also consist of desmopressin. Desmopressin is a synthetic hormone that stimulates the release of factor VIII contained within the structures of blood vessels. Doctors can use it in mild hemophilia to help manage a bleeding episode.
Results from a
Transfusions of fresh frozen human plasma or whole blood only take place if factor VIII concentrates are not available or there is a need to replace additional blood components.
Antifibrinolytic agents are supplementary medications to prevent blood clots from breaking down. Doctors
Tranexamic acid and aminocaproic acid are antifibrinolytic agents commonly used in hemophilia A.
Doctors consider genetic therapy and other second-line treatments for hemophilia A when a person develops inhibitors to traditional factor VIII replacement. Inhibitors are antibodies the immune system makes that attack replacement factor VIII as if it were a bacteria or virus.
Approximately 30% of people with severe hemophilia develop inhibitors.
Gene therapy
In hemophilia A, gene therapy aims to counteract the genetic alteration that causes factor VIII deficiency. Doctors do this by inserting a functional copy of the F8 gene into a person’s cells using vectors, small molecules that can deliver genetic material into a cell.
The most common vectors in gene therapy for hemophilia A are called adeno-associated virus (AAV) vectors. They use harmless viral variants as their mode of transport.
Gene therapy works by providing a functional copy of F8, which allows the body to produce its own factor VIII.
In 2023, the Food and Drug Administration (FDA) approved the one-time gene therapy Roctavian (valoctocogene roxaparvovec) for hemophilia A treatment. It uses an AAV vector to transport a functional copy of F8 into a person’s liver cells.
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Gene therapy may have more benefits than just providing clotting factor VIII. A 2023 review suggests gene therapy in hemophilia A can help reduce the presence of inhibitors through a process called immune tolerance induction (ITI).
In theory, by allowing the body to make its own controlled amounts of factor VIII with genetic modification, a person’s immune system could be trained to become more tolerant of synthetic factor VIII replacement.
Immunotherapies
Immunotherapies are treatments that target, modify, or enhance a person’s immune function to help treat hemophilia A.
One current targeted immunotherapy medication in hemophilia A is emicizumab.
Emicizumab is a
Sometimes, suppressing the immune system can benefit a person with inhibitors. In these circumstances, doctors use immunosuppressive treatments (ISTs). ISTs focus on eliminating inhibitor antibodies that compromise traditional therapies.
Standard medications in ISTS include:
- corticosteroids
- cyclophosphamide
- mycophenolate mofetil
- rituximab
Bypassing agents
Bypassing agents work to improve a person’s clotting function by enhancing other pathways involved in the clotting process. As with traditional replacement therapy, doctors can administer them on-demand or as prophylaxis treatment.
Examples of available bypassing agents include:
- activated prothrombin complex concentrates
- recombinant factor VIIa
Clinical trials use human volunteers to explore the safety, efficacy, and practicality of emerging therapies. Participating in a clinical trial provides an opportunity to work with a highly specialized medical team with access to otherwise unavailable therapies.
A person might be a candidate for a clinical trial if hemophilia A is not responding adequately to standard therapies or if access to traditional treatment is limited.
People can find clinical trials for hemophilia A by visiting:
With appropriate standard treatment,
New and emerging therapies can improve outcomes when inhibitors complicate first-line therapies.
Hemophilia A is a genetic bleeding disorder caused by a genetic alteration in the F8 gene, which results in clotting factor VIII deficiency. Without enough factor VIII, a person’s blood is unable to form stable clots, and bleeding can become prolonged.
Replacement of factor VIII is the mainstay of hemophilia A treatment. Doctors can supplement this with other therapies to support clotting processes and address challenges with the development of antibodies called inhibitors.
Gene therapy, immunotherapy, and bypassing agents are all second-line treatments that can help improve outcomes.