All people with hemophilia and VWD type 3 are at risk for developing an inhibitor – an antibody – to treatment used to stop or to prevent a bleeding episode.

Hemophilia and VWD type 3 are bleeding disorders in which the blood does not clot due to missing or low levels of proteins, known as ‘clotting factors,’ in the blood. People with hemophilia and VWD type 3 receive treatment products called ‘clotting factor concentrates’ to replace missing or low blood clotting factor in their blood. This procedure (known as infusion) is carried out by injecting commercially prepared clotting factor concentrates into their vein.

When a person develops an inhibitor, the body thinks that the clotting factor concentrates are harmful, foreign substances and rejects the clotting factor concentrates as treatment. Instead, the body tries to destroy the clotting factor concentrates with an inhibitor to protect the body, which makes it harder to treat a bleeding episode.

All persons with hemophilia and VWD type 3 are at risk of developing an inhibitor. Scientists do not know exactly what causes inhibitors. Multiple research studies have shown that people with certain types of hemophilia gene mutations are more likely to develop an inhibitor.

Genes are inside all cells in the body, and they contain the instructions for the development and functioning of all living things. The genes that a person inherits from his or her parents can determine many things. For example, genes affect what a person will look like and whether the person might have certain diseases. Hemophilia is caused by changes, called mutations, within the genes that control normal blood clotting.

Some studies have found other characteristics that possibly play a role in increasing the risk of inhibitor development among people with hemophilia. These include the following:

• Number of times one has used clotting factor concentrates in their lifetime,
• Increased frequency and dose of treatment,
• Black race or Hispanic ethnicity, and
• Family history of inhibitors (other family members who have had inhibitors).

Only a blood test can determine if an inhibitor is present and it can measure the amount present. Inhibitors are complex, and not everyone with hemophilia and VWD type 3 will develop an inhibitor. Researchers do not yet know why some people will develop an inhibitor and why some will not, but research studies are being conducted to learn more about them. Inhibitors can appear at any time, so it is important that all people with hemophilia and VWD type 3 be tested for an inhibitor each year.

Inhibitors are diagnosed with a blood test. The blood test measures if an inhibitor is present and the amount of inhibitor present (called an inhibitor titer) in the blood. Inhibitor titers are measured in Nijmegen-Bethesda units (NBU) if the lab test used was the Nijmegen-Bethesda assay (NBA), or Bethesda units (BU) if the lab test used was the Bethesda assay. A person with a high inhibitor titer has more inhibitor present in the blood compared to a person with a low inhibitor titer. Test results of 5.0 NBU/BU or lower are called “low titer” inhibitors, whereas test results of greater than 5.0 NBU/BU are called “high titer” inhibitors. People diagnosed with low titer inhibitors are more likely to have shorter and more successful inhibitor treatment than those with high titer inhibitors. For these reasons, it is important that all people with hemophilia or VWD type 3 who use clotting factor concentrates get tested for inhibitors at least once a year.

Treatment for people who have an inhibitor is complex, and it remains one of the biggest challenges in the care of people with bleeding disorders. Some inhibitors, called “transient” inhibitors, may disappear on their own, without treatment. If possible, a person with an inhibitor should consider seeking care at an HTC. HTCs are specialized healthcare centers that bring together a team of doctors (hematologists or blood specialists), nurses, and other health professionals experienced in treating people with bleeding disorders.

Some treatments for people with inhibitors include the following:

• High-Dose Clotting Factor Concentrates: People with low titer inhibitors may be treated with higher amounts or increased frequency of factor to overcome the inhibitor and yet have enough left over to form a clot.
• Bypassing Agents: Special blood products, called bypassing agents, are used to treat bleeding episodes for people with high titer inhibitors. Instead of replacing the missing factor, they go around (or bypass) the factors that are blocked by the inhibitor to help the body form a normal clot. Close monitoring of people taking bypassing agents is important to make sure that their blood is not clotting too much or clotting in the wrong places in the body.
• Products that mimic Factor VIII: This type of product works by replacing the function of factor VIII (8) without being affected by inhibitors, and can be used to treat and prevent bleeding episodes in people with hemophilia A. This treatment product can be given by injection under the skin.
• Immune Tolerance Induction (ITI) Therapy: The goal of ITI therapy is to stop the inhibitor from blocking factor in the blood and to teach the body to accept factor as a normal part of blood. With ITI therapy, people receive large amounts of factor every day for many weeks or months.

All inhibitor treatment options require specialized medical expertise. Treatment can be costly, particularly bypassing agents and ITI. It is important that people who are being treated for inhibitors have their blood tested often to measure their inhibitor titers to be sure that the treatment is working. HTCs can serve a vital role in supporting patients who undergo intensive treatment regimens, such as ITI, for inhibitors.

Treatment for people with an inhibitor poses special challenges. The healthcare costs associated with inhibitors can be staggering because of the amount and type of treatment product required to stop bleeding. Also, people with hemophilia who develop an inhibitor are twice as likely to be hospitalized for a bleeding complication, and they are at increased risk of death. The excess cost of care for each person with hemophilia and an inhibitor is over $800,000 per year and, based on CDC surveillance data, there are nearly 1,500 people living with an inhibitor in the United States.

Anthony was diagnosed with hemophilia A at the age of 3. He needed surgery to remove his appendix, and it was then when doctors learned that he had hemophilia. He began receiving treatment for hemophilia, and shortly after, he developed an inhibitor.

As a child, Anthony used clotting factor replacement products to treat bleeding episodes. He learned to self-infuse at an early age, but he never knew that an inhibitor could go away. He was often on crutches and was home schooled. “There were times in my teens when I was depressed because of hemophilia. I wanted to go to school and try out for basketball and football like my friends, but I knew I couldn’t,” says Anthony. He still wanted to play with his friends so he played basketball in the neighborhood, despite the risks, and it would often lead to pain in his joints, bruises, and jammed fingers.

Over time, he realized the importance of taking care of his body and looked for other activities. He chose to stop focusing on the things he wanted to do and began focusing on the things he could do. “I started producing and writing music. It took me from wanting to play sports to channeling that energy into something else that wouldn’t tear my body up,” says Anthony.

In his early 20s, Anthony began treatment at a hemophilia treatment center at Emory University. At Emory, he had a supportive team of doctors who developed a treatment plan for his inhibitor. This was the first time Anthony learned that he could beat an inhibitor. He was treated once a day, and they practiced infusing with him to help shorten his infusion time so that he would be more likely to keep his infusion schedule. It worked, and since receiving care at Emory, Anthony’s inhibitor levels have been so low that the inhibitor is almost undetectable.

Today, Anthony continues to produce and write music. It went from a hobby to a career, and hemophilia doesn’t slow him down. He travels and performs on stages across the United States. When he’s not performing, he’s at home with his family or participating in hemophilia conferences and events. “To me, hemophilia is just a side thing. It’ll only hold me down if I let it.”

For families with hemophilia, Anthony encourages them to join a support community. “Sometimes it’s hard, and it feels like you can’t relate to anyone else but support communities help. I’ve been there. I’ve lived with hemophilia all my life. As long as you have a good support team, you can do anything,” says Anthony.

“I tell parents to embrace their child being different. I want the younger generation to preserve their bodies to be able to live without worrying about a wheel chair when they’re an adult. They don’t have to play basketball or football to have fun. I took music and made it something I like to do. Sometimes when you’re different, people want to do what you’re doing, so just embrace it. There’s a lot going on with hemophilia right now, and it’s a bright future for our community.”

CDC would like to thank Anthony for sharing his personal story.