WFH NETWORK

What are the treatment options for inhibitors?

People with inhibitors are more difficult to manage and treat than people without inhibitors. There are a number of different approaches. Decisions regarding treatment should take into account the person's inhibitor titer and anamnestic response, the site and severity of the bleed, and whether he/she has started or is planning to start immune tolerance induction therapy. Ideally, a person with inhibitors should be treated at a hemophilia treatment centre with specialized expertise.

High-dose factor concentrates
Administering factor concentrates at higher doses and/or more frequent intervals is the preferred treatment for acute bleeding in low responders. The person's factor level should be measured right after each infusion to make sure that target levels are reached. Continuous infusion may be useful. High-dose factor concentrate is also the preferred treatment option for acute bleeding in previous high responders with current low titer inhibitors — however, it is vital to take into account that the anamnestic response will get stronger within five to seven days, at which time treatment should be switched to bypassing agents.

Bypassing agents
Bypassing agents, such as activated prothrombin complex concentrates (APCC) and recombinant factor VIIa (rFVIIa), are used to treat acute bleeding in people with high titer inhibitors. However, these treatment products are expensive and not always available in every country.

  • APCCs like Factor Eight Inhibitor Bypassing Agent (FEIBA®) are made from human plasma and contain variable amounts of clotting factors such as factor VII, factor IX, and factor X. Treatment is given frequently (usually every eight to twelve hours) but should be limited to a maximum of five consecutive doses. A risk of blood clot formation has been associated with its use.
  • rFVIIa (NovoSeven®) is a synthetic product that also has to be administered frequently (usually every two to three hours), which can lead to problems with access to veins.

Tranexamic acid
Tranexamic acid is an antifibrinolytic drug that can be given as an additional therapy in pill form or by injection to help stop blood clots from breaking down. It is particularly useful for bleeding that involves mucous membranes such as those in the nose or mouth. However, it should not be used in combination with APCCs.

Epsilon aminocaproic acid (AMICAR™)
Epsilon aminocaproic acid is an antifibrinolytic drug that can be given as an additional therapy in pill form or by injection to help hold clots in place in certain parts of the body, such as the mouth, bladder, and uterus.

Plasmapheresis
Plasmapheresis is a procedure that removes inhibitors from the person's bloodstream. It is usually done when the inhibitor titer needs to be brought down quickly (for example, before major surgery or in cases of severe bleeding that are not well controlled with bypassing agents).

Immune tolerance induction therapy
Immune tolerance induction (ITI) therapy involves giving the person with inhibitors frequent doses of factor concentrates over several months, or sometimes years, to train the body to recognize the treatment product without reacting to it. This process is called tolerance induction. If a person plans to undergo immune tolerance induction therapy, but has not yet started, it is better not to use factor products to treat acute bleeding episodes because they are likely to provoke a rise in inhibitor titer.

Content developed by the WFH Inhibitors Working Group


Updated May 2012