Inhibitors do not develop in everyone with a bleeding disorder, but they can have a serious impact on those people who do have one. Often people do not demonstrate symptoms unless they experience a bleeding episode. Yet, detecting an inhibitor early will help you have a better chance at eliminating it.
This section of Inhibitors will cover:
Who Is More Likely to Develop an Inhibitor?
What Are the Symptoms of an Inhibitor?
How Do You Test for an Inhibitor?
What Is an Inhibitor?
The immune system helps protect your body and keep it healthy by fighting off bacteria and viruses that can cause illnesses. An unknown substance that enters your body is called an antigen. When the antigen comes into your body it activates an immune response. Your body will produce antibodies to fight off the antigen. Sometimes, the immune system attacks the wrong target1.
Inhibitors happen when your body’s immune system targets your bleeding disorder medication as an unfamiliar substance, or antigen. Your body then creates an antibody against your bleeding disorder medication. This antibody is called an inhibitor. The antibody, or inhibitor, attacks your bleeding disorder medication by binding to it. Your medication will inactivate and is no longer able to perform its intended job of stopping bleeding. Inhibitors do not affect the location, frequency, or severity of bleeds. They do make bleeds more difficult to control1.
Who Is More Likely to Develop an Inhibitor?
Experts are not clear on the exact reason why someone has an inhibitor. Currently, there is no effective method of predicting who will develop an inhibitor. Still, most researchers agree that it can be linked to a combination of factors like your genes, your family and health history, and other aspects like the type of product, and treatment intensity 2,3,4,5.
Inhibitors most commonly occur in people with hemophilia but can also happen in people with von Willebrand disease (type 3). It is estimated that about 30 percent of people with severe hemophilia A may develop an inhibitor at some point in their lives. It is thought to affect about 4% of people with severe hemophilia B. There are some additional factors which are believed to increase the potential of developing an inhibitor. These include:
- People with severe hemophilia
- People who are Black and Hispanic
- People who have a family member with an inhibitor
- People with certain genetic mutations of hemophilia
Inhibitors most commonly develop within the first 50 exposures to treatment. Since many people with severe bleeding disorders will begin treatment when they are young, it frequently develops during childhood. However, inhibitors can occur later in life as well. This is more often seen in people with milder bleeding severity. It is important to test for the presence of an inhibitor regularly4.
What Are the Symptoms of an Inhibitor?
Signs and symptoms of an inhibitor include frequent bleeds while on a regular treatment schedule, and/or lack of response to treatment. If you have an inhibitor, you may not get better after receiving your normal medication or the bleeding may take longer to stop. Some people have also experienced allergic reactions or anaphylaxis. This has been mostly seen in people with hemophilia B. However, inhibitors are frequently difficult to detect and may go unnoticed for quite some time. It is recommended to test for inhibitors regularly1,2.
If you want more information about the testing recommendations, please go to MASAC Document 236.
How Do You Test for an Inhibitor?
The most common test used to diagnose an inhibitor is a blood test called the Bethesda inhibitor assay. It can be ordered by your health care provider at your Hemophilia Treatment Center (HTC). If you get a positive result on the Bethesda assay it means you have an inhibitor. The inhibitor that you have is working against your bleeding disorder medication. There is the possibility of a false positive test result. In this case a second test is completed 1.
The amount of an inhibitor in a person’s blood is called a titer. The titer is measured in Bethesda units. If you have more than five Bethesda units, you have a high-titer inhibitor. This means your body has a strong response against your medication. If you have less than five Bethesda units, you have a low-titer inhibitor. This means your body does not have a strong response to your medication1. If your test result shows that you have an inhibitor, your health care provider will discuss options for treatment and management. Together you will design the best plan of care for you. If you want more information about how inhibitors can be treated, please go to Managing Inhibitors.
National Bleeding Disorders Foundation (NBDF) has developed helpful resources to provide you with information about inhibitors and how to manage having an inhibitor. Check out these publications to learn more:
NBDF also provides in-person inhibitor focused education during the annual Bleeding Disorders Conference. To lessen the burden attendance costs, travel grants are available. If you want more information about these, please go to the Bleeding Disorders Conference website.
- DIMICHELE. (2002). Inhibitors: resolving diagnostic and therapeutic dilemmas. Haemophilia: the Official Journal of the World Federation of Hemophilia, 8(3), 280–287. https://doi.org/10.1046/j.1365-2516.2002.00626.x
- Oldenburg, Schröder, J., Hermann Brackmann, H., Müller-Reible, C., Schwaab, R., & Tuddenham, E. (2004). Environmental and genetic factors influencing inhibitor development. Seminars in Hematology, 41(1), 82–88. https://doi.org/10.1053/j.seminhematol.2003.11.016
- Ragni, M., Ojeifo, O., Feng, J., Yan, J., Hill, K. A., Sommer, S. S., Trucco, M. N., & Brambilla, D. J. (2009). Risk factors for inhibitor formation in haemophilia: a prevalent case-control study. Haemophilia: the Official Journal of the World Federation of Hemophilia, 15(5), 1074–1082. https://doi.org/10.1111/j.1365-2516.2009.02058.x
- van den Berg, Fischer, K., Carcao, M., Chambost, H., Kenet, G., Kurnik, K., Königs, C., Male, C., Santagostino, E., & Ljung, R. (2019). Timing of inhibitor development in more than 1000 previously untreated patients with severe hemophilia A. Blood, 134(3), 317–320. https://doi.org/10.1182/blood.2019000658
- Wroblewska, Reipert, B. M., Pratt, K. P., & Voorberg, J. (2013). Dangerous liaisons: how the immune system deals with factor VIII. Journal of Thrombosis and Haemostasis, 11(1), 47–55. https://doi.org/10.1111/jth.12065