Factor VIII replacement therapy for hemophilia A
Fact-checked by Factor VIII (FVIII) replacement therapy is a cornerstone of treatment for many people with hemophilia A, a rare bleeding disorder caused by deficient or dysfunctional FVIII, a protein needed for blood clotting.
Because people with hemophilia A have reduced FVIII activity, they are prone to prolonged bleeding after injuries, surgery, or dental procedures. Those with severe disease may also experience spontaneous bleeding into joints and muscles.
FVIII replacement therapy is a treatment approach in which a version of the deficient FVIII protein is infused into the bloodstream to help the blood clot more normally. It can be administered on demand to control an active bleed or prophylactically, on a regular schedule, to prevent bleeds.
Multiple factor replacement products are available for people with hemophilia A. They differ in how they are produced, how long they remain active in the body, and how often they need to be administered. People with hemophilia A should work closely with their healthcare team to select a product and treatment schedule that suits their individual needs and preferences.
Recombinant vs. plasma-derived products
FVIII replacement products are categorized as either plasma-derived or recombinant, depending on how they are produced.
- Plasma-derived: Products that contain clotting factors isolated from donated human plasma. Examples include Alphanate, Humate-P, Koāte, and Wilate.
- Recombinant: Products manufactured in the lab using DNA technology and specially engineered cells, rather than being collected from donated human blood. Examples include Advate, Adynovate, Afstyla, Altuviiio, Eloctate, Esperoct, Jivi, Kovaltry, Novoeight, Nuwiq, Obizur, and Xyntha.
While both types of products are highly effective for controlling and preventing bleeds, they have distinct characteristics that should be considered when selecting a treatment.
For example, although donor blood is rigorously screened and processed before use, plasma-derived products carry a theoretical risk of contamination with infectious agents, such as viruses, due to their human origin. Because recombinant FVIII products are made in the lab, they eliminate the risk of transmitting known blood-borne infections. However, with modern safety practices, this risk difference is negligible.
Recombinant products also come in extended half-life formulations, which allow for less frequent dosing. Plasma-derived factor concentrates, on the other hand, are generally more affordable and may be more commonly used in resource-limited areas where recombinant products are inaccessible.
Finally, some data suggest that, in previously untreated people with severe hemophilia A, plasma-derived products may be less likely than recombinant products to trigger the production of neutralizing antibodies, called inhibitors, that make the therapy less effective. However, this is an area of active study.
Standard half-life vs. extended half-life products
When using a recombinant product, patients may need to choose between two types: standard half-life (SHL) or extended half-life (EHL) products.
- SHL products: Contain FVIII molecules that remain in circulation for approximately the same amount of time as natural FVIII. Most people receiving prophylaxis with these products require infusions several times per week. Examples include Advate, Kovaltry, Novoeight, Nuwiq, Obizur, and Xyntha.
- EHL products: Contain FVIII proteins modified to remain active in the bloodstream for longer, enabling less frequent dosing. Examples include Adynovate, Afstyla, Altuviiio, Eloctate, Esperoct, and Jivi.
Various modifications may be used to help EHL products stay active longer, including:
- albumin fusion
- Fc fusion
- PEGylation
- XTENylation
- fusion with the von Willebrand factor
Although treatment schedules with either product type can vary widely, EHL products may reduce the treatment burden for some patients by allowing less frequent infusions, which could make it easier to follow a treatment plan.
EHL therapies may also help keep FVIII levels more stable, lowering the risk of breakthrough bleeds between infusions. However, EHL products may be more expensive than SHL products.
Establishing a prophylactic infusion schedule
Prophylactic treatment is generally recommended for people with more severe hemophilia who are prone to significant bleeding. Patients should work with their care team to determine the appropriate infusion schedule, which can vary based on:
- the product being used
- the person’s age
- bleeding history
- FVIII activity levels
- physical activity level
- treatment goals
Infusions can be given by a healthcare provider or self-administered at home after proper training.
Typically, SHL therapies are administered two to four times a week, and EHL therapies are given once or twice a week, though infusions can be more or less frequent based on individual needs. For example, children tend to clear FVIII from the bloodstream faster and may require more frequent infusions.
Additional clotting factor infusions beyond the set schedule may also be recommended around surgery, dental procedures, or other situations where the risk of bleeding is increased, as well as to treat breakthrough bleeding episodes.
Monitoring treatment success
Patients receiving FVIII replacement therapy should be regularly monitored by their care team to ensure the treatment is working as intended. Doctors will look at two main things:
- Clinical outcomes: Clinicians will ask about the frequency and severity of hemophilia A symptoms, including bleeds and pain, as well as quality of life. They may also ask whether the patient is following the treatment plan as prescribed.
- FVIII activity levels: Laboratory tests will measure FVIII activity levels and other aspects of blood clotting to determine whether treatment continues to provide adequate protection against bleeding.
If symptoms have worsened or FVIII activity is not increasing to a level needed for bleed control, a doctor may recommend adjusting the dose or frequency of an existing medication or switching to a new one.
Doctors may also test for inhibitors, which can make FVIII replacement therapy less effective. If inhibitors develop, other treatments can help the blood clot through mechanisms that don’t rely on FVIII.
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.
