An inhibitor-against-factor concentrate is formed when the body's immune system recognizes the factor as a foreign substance. As a result, antibodies are made that attack the factor concentrate, making it ineffective in treating bleeding episodes. Although anyone can develop an inhibitor, genetics play a major role in the risk of developing an inhibitor. Some patients with inhibitors tend to have similar gene mutations. These mutations are also typically found in patients with severe hemophilia.

Diagnosing inhibitors

Inhibitors are found in 25-50 percent of people who have Hemophilia A or factor VIII deficiency; and 1.5-5 percent of people who have Hemophilia B, or factor IX deficiency. Inhibitors-against-factor concentrate generally develop at a young age – usually within the first nine to 50 infusions. Some inhibitors are diagnosed when a patient presents with a bleeding episode that is not improved with their usual factor replacement. Other inhibitors are diagnosed on routine testing of blood work.

Measuring inhibitors

Inhibitors are measured in "Bethesda units." One Bethesda unit equals the amount of antibody that neutralizes 50 percent of the factor activity. Some patients will develop "low-titer" inhibitors, meaning their Bethesda units are never greater than 5. Some "low-titer" inhibitors may be temporary and go away on their own. "High-titer" inhibitors are patients with Bethesda units greater than 5. High titer inhibitor patients may have very low Bethesda if they have not recently received their missing factor replacement. However, shortly after receiving factor VIII or Factor IX, inhibitor titers rise quickly to levels above 5BU.

Eliminating inhibitors

"Immune tolerance" is a process of trying to eliminate an inhibitor. There are different programs used in immune tolerance, each with varying success rates and length of time needed to eliminate or weaken the inhibitor. Immune tolerance therapy can take months to years to achieve and is costly. Though immune tolerance therapy is successful in getting rid of inhibitors 75 percent of the time, there are some people who are resistant to the treatment.

If a person is unsuccessful at eliminating an inhibitor or is unable to participate in immune tolerance therapy, there are a number of treatment options, depending on the type of bleeding episode and his or her current Bethesda Assay. Your physician will help decide which treatment is best for you. Management of hemophilia patients with inhibitors is complex and should be managed by an experienced hemophilia team of experts.

Those who are unable to use factor VIII (8) or factor IX (9) concentrates have several "bypassing" factor products available to help them during a bleeding episode. Bypassing products work with platelets and other factor proteins to help your blood clot, thus they "bypass" the need for factors VIII or IX. There are several different types of bypassing products, including:

• Prothrombin Complex Concentrates –Bebulin VHâ, Profilnine SDâ
• Activated Prothrombin Complex Concentrates-Feiba VH®
• Recombinant activated factor VII (7)-NovoSeven®

Porcine Factor VIII (Hyate C®) is made from pigs. For some inhibitor patients, it may be an option for treatment. The supply of Hyate C is very low and reserved for life-threatening bleeding episodes. A recombinant form of Porcine Factor VIII is undergoing clinical trials and may be a potential therapy in the future.