Hemophilia A is a rare bleeding disorder in which the blood doesn’t clot properly. Some people who receive treatment develop inhibitors, which are immune proteins that attack infused clotting factors. This can make treatment harder to manage.

Here’s what to know about inhibitors in hemophilia A, including how they’re diagnosed and treated.

What Are Inhibitors in Hemophilia A?

People with hemophilia A have low levels of a clotting factor called factor VIII (8). Clotting factors are usually written with Roman numerals. The lower the levels of clotting factors in the blood, the more severe hemophilia will be.

🗳️ Which has worked best for you to help manage inhibitors in hemophilia A?

High-dose clotting factor concentrates

Bypassing agents (BPAs)

Immune tolerance induction (ITI) therapy

Nothing has worked well to manage inhibitors.

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Hemophilia treatments help replace missing blood-clotting factors or help the blood clot in another way.

Some people receive infusions of clotting factor concentrates that are either plasma-derived (from donated human blood) or recombinant (made in a lab) to help their blood clot and prevent bleeding episodes.

Others, including many people with inhibitors, use nonfactor therapies. These treatments don’t replace factor VIII, but they still help blood clot in a different way.

Inhibitors are antibodies — proteins made by the immune system — that target infused clotting factors. Normally, the immune system makes antibodies to target harmful substances like bacteria or viruses to help destroy them and keep us healthy.

Sometimes, the immune system makes antibodies against substances that are harmless or helpful, such as clotting factors used to treat hemophilia. These antibodies are called inhibitors because they block clotting factors from helping the blood clot.

Inhibitors can keep treatment from working. This can lead to uncontrolled bleeding and make hemophilia harder to manage.

Living With Inhibitors

MyHemophiliaTeam members have shared their questions and experiences with developing inhibitors.

One member asked, “I’m getting curious if I could possibly have developed an inhibitor. Is that likely at my age? I’ve been infusing a lot lately, and nothing seems to be changing.”

Others have shared experiences of their loved ones developing inhibitors. “I’m the uncle of a toddler diagnosed with severe hemophilia A. During the last week, we discovered that my nephew has inhibitors,” wrote one member.

Another responded, “That really sucks, but there is hope. My son had the same problem. They gave him a 100 percent clotting factor per pound for about one or two years, and he no longer has an inhibitor.”

Why Does a Person Develop Inhibitors?

The risk of developing inhibitors mainly depends on the type and severity of hemophilia you have. According to the Hemophilia Federation of America, around 30 percent of people with severe hemophilia A will develop inhibitors at some point.

Typically, inhibitors develop during childhood, especially within the first 50 infusion treatments. In some cases, inhibitors may develop later in life after treatment is complete, but this is rare.

Although it’s less common, people with mild to moderate hemophilia can also develop inhibitors. It’s estimated that between 5 percent to 8 percent of those with mild to moderate hemophilia A may develop inhibitors.

It’s less common to develop inhibitors with hemophilia B. This only happens in 2 percent to 3 percent of cases.

Certain risk factors can increase the likelihood of developing inhibitors. According to the Hemophilia Federation of America, these include:

• Being of African American or Hispanic descent
• Having a family history of inhibitors
• Receiving higher doses of clotting factors due to trauma or surgery
• Being younger
• Having certain gene mutations (changes)

Inhibitor Testing and Monitoring Frequency

The most obvious symptom of having inhibitors is uncontrolled bleeding that doesn’t stop even after treatment with clotting factor. This is called breakthrough bleeding. Your body also may not heal as well after an injury.

If your doctor thinks you may have inhibitors, they’ll order a blood test called the Bethesda assay. This test is often done using a version called the Nijmegen-modified assay. This test, also known as an inhibitor titer, measures how much inhibitor is in the blood.

To be safe, it’s recommended that people with hemophilia and von Willebrand disease type 3 get tested once a year for inhibitors. Inhibitor symptoms aren’t always obvious, so testing is important to monitor for their development.

According to the Centers for Disease Control and Prevention (CDC), free inhibitor testing is offered through federally funded hemophilia treatment centers to those who qualify.

People with inhibitors are categorized based on the concentration of inhibitors. They either have low-titer (low-responding) inhibitors or high-titer (high-responding) inhibitors.

A person with low-titer inhibitors is more likely to respond well to inhibitor treatment. Those with high-responding titers are less likely to have successful treatment.

How Are Inhibitors Treated?

Inhibitors can be challenging, but treatment options can help many people. Options may include high-dose clotting factor concentrates, bypassing agents (BPAs), and immune tolerance induction (ITI) therapy.

Treatments for Low-Titer Inhibitors

If you have low-titer inhibitors, your doctor may give you high doses of clotting factor concentrates.

Higher doses can help overcome inhibitors in your blood and give your body more clotting factor so your blood can clot. You may need treatments more often for this method to work.

Treatments for High-Titer Inhibitors

High-titer inhibitors can make treatment more complicated. Your doctor will consider the type of hemophilia you have and how severe your bleeding is when making a treatment plan.

In an emergency, plasmapheresis can filter high concentrations of inhibitors out of the blood. However, this is only a temporary solution, as the body will continue to make new inhibitors.

One class of treatments, called bypassing agents, helps blood clot without using factor VIII.

To date, the U.S. Food and Drug Administration (FDA) has approved a few BPAs to treat people with inhibitors, including:

• Coagulation factor VIIa (7a) (recombinant) (NovoSeven RT) — Used in people who have developed inhibitors against factor VIII or factor IX (9), this treatment activates a different clotting pathway in the body.
• Anti-inhibitor coagulant complex (Feiba) — This medication contains a combination of factors IIa (2a), VIIa, IXa (9a), and Xa (10a) to help clot blood.
• Coagulation factor VIIa, (recombinant)-jncw (Sevenfact) — This medication contains a synthetic, or human-made, version of factor VIIa used to treat people with hemophilia A or B.

Nonfactor Prophylaxis for People With Inhibitors

Some people with hemophilia A and inhibitors use a different type of treatment called nonfactor prophylaxis. These medicines don’t replace factor VIII. Instead, they help the blood clot in other ways.

FDA-approved nonfactor therapies are injected under the skin. Options currently include:

• Emicizumab-kxwh (Hemlibra) — This antibody brings together factor IXa and factor X (10) to mimic the role of factor VIII, helping blood clot without replacing the missing factor. It’s approved for prophylaxis in people with hemophilia A, with or without inhibitors.
• Fitusiran (Qfitlia) — This antibody works by lowering antithrombin, a protein that normally slows clotting. It’s approved for adults and adolescents (12 and older) with hemophilia A or B, with or without inhibitors.

MyHemophiliaTeam members have shared their experiences with nonfactor prophylaxis.

One member wrote, “I’m on Hemlibra now and have been bleed-free for a little over two years. Hemlibra has changed my life.”

Another said, “I’ve been on Hemlibra for months with no treatable bleeds and no side effects.”

Immune Tolerance Induction Therapy

To target the cause of inhibitors, some people undergo immune tolerance induction therapy. ITI therapy makes the immune system get used to clotting factors, so it doesn’t make antibodies against them.

During ITI therapy, clotting factors are given every day for weeks or months. This helps train the immune system to accept them.

Your doctor may also prescribe medications that suppress the immune system so it doesn’t overreact during ITI therapy.

ITI therapy is generally successful in people with hemophilia A and inhibitors. Around 70 percent become tolerant to infused clotting factors. On the other hand, this treatment only works in around 30 percent of those with hemophilia B and inhibitors.

Talk to Your Doctor About Inhibitors

Depending on the type of hemophilia you have, you may be at a higher risk of developing inhibitors. Talk to your healthcare provider about yearly testing and what it could mean if you develop an inhibitor to your treatment.

The cost of inhibitor treatment can be expensive, especially when combined with other hemophilia treatments. If you’re worried about the cost of treatment, talk with your doctor. They can connect you with a hemophilia treatment center or social worker who can help you learn more about coverage, costs, and any available resources.

Join the Conversation

On MyHemophiliaTeam, people share their experiences with hemophilia, get advice, and find support from others who understand.

Have you or your loved one with hemophilia had success treating inhibitors? Let others know in the comments below.