Inhibitors

In rare instances, people with hemophilia B can develop an inhibitor to standard factor treatment. Only about 3% to 5% of patients with severe hemophilia B develop an inhibitor, a much lower incidence than in severe hemophilia A.

Inhibitors most often develop during childhood, especially during the first 50 exposure days (the period of time after starting a replacement therapy for hemophilia that an individual may develop an inhibitor; if the individual does not develop an inhibitor during this time, it is unlikely that an inhibitor will develop). The risk of developing an inhibitor is higher if someone in the patient's family also has an inhibitor. In addition, development of an inhibitor is more frequent among African Americans.

How do inhibitors develop?

Inhibitors develop as a result of an abnormal immune response to replacement therapy.

The role of the immune system is to protect the body from disease. When a foreign substance (such as a virus or bacteria) finds its way past barriers like the skin and mucus membranes, the immune system launches a cellular response and produces antibodies. In most cases, antibodies are able to destroy the foreign substances.

People with hemophilia B may be unable to produce the coagulation protein needed for this to happen. In some cases, when a person with hemophilia B receives replacement therapy, the body's immune system will perceive the normal clotting factor as different from itself or as an antigen to which an antibody is produced. These antibodies are called inhibitors. The inhibitor binds itself to the infused clotting factor making it difficult, if not impossible, to obtain enough clotting factor to control bleeding.

Often, a person will not have symptoms associated with the presence of an inhibitor. In these cases, inhibitors are likely to be discovered by laboratory testing during regular physician visits. For those who are symptomatic, an inhibitor is usually suspected when bleeding does not stop after being treated with factor concentrate. Once an inhibitor is suspected, confirmation is made using a blood test called the "Bethesda inhibitor assay." This test measures the presence and amount of antibodies directed against a coagulation factor in a person's blood after being exposed to factor.