The most dreaded complication of hemophilia treatment is the formation of an antibody to the normal clotting factor being given as therapy. These antibodies, called “inhibitors”, arise in approximately 30% of people with severe hemophilia A at some point in their lives.
An inhibitor usually occurs between the 5th and 50th infusion of factor concentrate, but in rare cases can also be developed later in life.
While people with severe hemophilia are more likely to develop inhibitors, approximately 5-8% of people with mild or moderate hemophilia A develop inhibitors. The antibodies destroy not only the factor concentrate infused but also the small percentage of factor protein that the body was producing naturally. So, a person with mild or moderate hemophilia who develops an inhibitor now, in effect, has severe hemophilia (<1% circulating factor).
Approximately 2-3% of people with hemophilia B develop inhibitors. While inhibitors in people with hemophilia B are less common than hemophilia A, it can be even more challenging as about half of hemophilia B inhibitor patients will develop an anaphylactic reaction to infused factor IX, which can be life-threatening.
Patients with inhibitors require careful attention. Treatment of a hemorrhage may require very high doses of the deficient clotting factor, or use of a so-called “bypassing agent”, a plasma-derived concentrate containing several activated clotting factors, or a recombinant activated factor VII.
Inhibitors sometimes can be eliminated by giving the patient very high doses of the clotting factor every day for many months. This program is called “immune tolerance induction”. It is successful in about 75% of patients, in OHTC’s experience.
At OHTC we measure inhibitor levels in the coagulation laboratory by a test, the Bethesda test, standardized in the 1970’s. Results are in Bethesda units, BU. Normally, we measure the degree to which the plasma containing an inhibitor destroys normal human factor VIII (or IX).