Inhibitors

Inhibitors

Normally, the body’s immune system works to fight off bacteria, viruses, and other foreign substances that can cause illness. Sometimes, however, the immune system attacks the wrong target.

Inhibitors (also called antibodies) occur when your body’s immune system targets factor replacement products. When this happens, the clotting factor is inactivated and unable to effectively perform its job in stopping bleeding. Inhibitors do not affect the location, frequency, or severity of bleeds, but they do make them more difficult to control.

Who’s At Risk for Developing an Inhibitor?

Inhibitors are common in patients with hemophilia—they occur in 15% to 20% of people with hemophilia A (factor VIII [8] deficiency) and 2% to 5% of people with hemophilia B (factor IX [9] deficiency). They can also occur in people with other types of bleeding disorders.

Because inhibitors usually occur within the first 50 days of exposure to treatment, they frequently develop during childhood. In people with mild hemophilia A, however, inhibitors often occur in or are not recognized until adulthood. Any person with a bleeding disorder can develop an inhibitor at any time, but it is usually in the first year or two of life. Having recently initiated treatment with factor replacement products can trigger the development of inhibitors but there are some other variables that can increase the risk of inhibitor development. A person is more likely to develop an inhibitor if he:

  • Has hemophilia A rather than hemophilia B
  • Has severe, rather than mild or moderate hemophilia
  • Is black or Hispanic
  • Has a family history of inhibitor development

Measuring Inhibitors

People who have inhibitors are usually described as high responders or low responders.

  • High Responders. Individuals are considered high responders if the amount of inhibitor in the blood increases quickly after factor is administered. This makes treatment with standard clotting factor difficult. High responders may need a different type of treatment, such as a bypassing agent and may need to undergo immune tolerance induction (ITI)
  • Low Responders. Individuals are considered low responders if the amount of inhibitor does not increase after factor is administered. Low responders are usually able to use standard clotting factor treatment but may need to receive higher doses than standardly given or repeated doses. ITI is also used for low responders if the inhibitor does not go away on its own

Managing Inhibitors

Treating people with an inhibitor is complex and remains one of the biggest challenges in hemophilia care today. (Sometimes inhibitors occur for a short time and then disappear spontaneously. Inhibitors that persist can increase the risks associated with bleeding episodes because factor therapy becomes less effective.) After a new treatment schedule is established, the blood’s factor level must be measured to see if the inhibitor goes away. If feasible, a person with an inhibitor should be cared for under the supervision of a Hemophilia Treatment Center (HTC).

Some treatments for people with inhibitors include:

  • High-dose clotting factor. People who have low-responding inhibitors may need larger amounts of clotting factor. Although some factor binds to the inhibitor and becomes inactive, enough is left to help form a clot
  • Bypassing agents. Bypassing agents are used to treat bleeding in people with high-titer inhibitors. Instead of replacing the missing factor (factor VIII [8] or factor IX [9]), they go around (or bypass) the inhibitor to help the body form a normal clot. People taking bypassing agents should be monitored closely to make sure their blood is not clotting too much or clotting in a wrong place in the body
  • Immune tolerance induction (ITI) therapy. The goal of ITI therapy is to stop the inhibitor reaction from happening. In a way, it teaches the body to accept clotting factor treatments. With ITI therapy, people receive large amounts of clotting factor every day for many weeks or months. ITI therapy requires specialized medical expertise, is costly, and may take a long time to work. In many cases, ITI does get rid of the inhibitor. But, patients may need to continue taking frequent, large amounts of factor for many years to keep the inhibitor from coming back