Hemophilia with Inhibitors
Hemophilia with Inhibitors

Hemophilia with inhibitors

Inhibitors are antibodies that are made by our immune system. In general, when your immune system identifies a foreign substance, it makes antibodies that will specifically recognize that substance and destroy it to defend you from harmful diseases and/or illnesses. Because the immune system thinks the foreign substance is attacking the body, antibodies — or inhibitors — are produced to destroy that substance. Sometimes the immune system makes a mistake and produces an inhibitor that destroys natural protectors of the body. Scientists aren't sure why this happens.1

When these inhibitors attack the clotting factor, the inhibitors neutralize the factor therapy and stop it from working.1 Since the hemophilia still needs to be treated, other treatment options need to be considered.2

The good news is that there are treatment options available to help manage bleeding episodes in hemophilia patients who develop inhibitors. People who have hemophilia with inhibitors can learn to successfully manage their hemophilia and lead happy lives.3

Having an inhibitor does not lead to more frequent bleeding episodes than those with hemophilia who do not have inhibitors.4

Who develops factor VIII or factor IX inhibitors?

  • Between 20% and 30% of severe hemophilia A patients and 5% to 10% of patients with mild/moderate hemophilia A develop factor VIII inhibitors2
  • Inhibitors are much less likely to develop in hemophilia B, occurring in less than 5% of all patients2

Inhibitors can develop quickly after beginning treatment with factor medicines—usually within the first 5-50 days. Having an inhibitor makes it hard to use factor medicine for successful treatment.1

"If you've had more than 50 factor exposures, then your chances of developing inhibitors are less." — Susana, Takeda community educator

Who is at higher risk of developing inhibitors?

Certain factors may increase the chances that an inhibitor will develop.1

Certain genetic factors may increase the chances that an inhibitor will develop
    Genetics1
  • A family history of inhibitors
  • African or Latino heritage
  • Severe hemophilia (as opposed to mild or moderate hemophilia)
  • People with hemophilia with large genetic mutations
Risk of inhibitors developing is higher early in treatment.
    Timing5
  • Risk of inhibitors developing tend to happen early in treatment, usually within the first 10-20 days after starting factor replacement treatment
  • Inhibitors tend to appear after surgery and intensive factor replacement treatments with high doses
Inhibitors usually develop before the age of 5 years
    Age1
  • Inhibitors usually develop before the age of 5 years, after having received a few factor replacement treatments

The general risk guidelines show a higher chance of children with severe hemophilia developing inhibitors. Yet, the truth is, inhibitors cannot be prevented, and they can happen at any time.1,6

Inhibitor testing: the Bethesda assay

An inhibitor is suspected whenever a bleeding episode is not controlled by a patient's usual dose of replacement clotting factor. Inhibitors are also diagnosed in individuals without symptoms based on the results of routine blood tests.6

Inhibitors are measured using a test called the Bethesda assay, which gives a numeric value and refers to the inhibitor level. This number is quantified in Bethesda units per milliliter (BU/mL) and refers to the inhibitor level. Knowing the level is important. It helps the hemophilia care team decide the best type of treatment to use.6

Inhibitor levels vary from person to person. Over the course of time, inhibitor levels can also vary within the same person.1

Are all inhibitors the same?

Inhibitors are divided into 2 categories based on the Bethesda assay and whether the inhibitor level increases when a patient is treated with replacement clotting factor:

Low-responding inhibitiors remain less than 5 BU/mL

Low-responding inhibitors remain less than 5 BU/mL. These inhibitors may be transient and disappear.1,7

High-responding inhibitors are equal to or greater than 5 BU/mL

High-responding inhibitors are equal to or greater than 5 BU/mL at any time. In the absence of replacement clotting factor exposure, high-responding inhibitors may decrease or become undetectable. However, when the patient is re-exposed to replacement clotting factor, this inhibitor level will increase over 4 to 7 days. This increase is termed anamnesis and is a hallmark of the high-responding inhibitor.1,3,7

There's help for inhibitors, too

You're not alone. More than 30% of hemophilia patients face inhibitors to their treatment.

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  1. Canadian Hemophilia Society. All about inhibitors. https://www.hemophilia.ca/files/All%20About%20Inhibitors.pdf. Accessed August 26, 2019.
  2. Srivastava A, Brewer AK, Mauser-Bunschoten EP, et al; Treatment Guidelines Working Group on Behalf of The World Federation of Hemophilia. Guidelines for the management of hemophilia. Haemophila. 2013;19(1):e1-47. http://www1.wfh.org/publications/files/pdf-1472.pdf. Published January 2013. Accessed August 26, 2019.
  3. Kempton CL, White GC. How we treat a hemophilia A patient with a factor VIII inhibitor. Blood. 2009;113(1):11-17. http://www.bloodjournal.org/content/113/1/11. Published 2009. Accessed August 26, 2019.
  4. How bleeding is stopped when a person has an inhibitor. The Hemophilia, von Willebrand Disease & Platelet Disorders Handbook website. https://www.hog.org/handbook/article/4/17/how-bleeding-is-stopped-when-a-person-has-an-inhibitor. Accessed August 26, 2019.
  5. Collins PW, Chalmers E, Hart DP, et al; UK Haemophilia Centre Doctors. Diagnosis and treatment of factor VIII and IX inhibitors in congenital haemophilia: (4th edition). Br J Haematol. 2013;160(2):153-170. https://onlinelibrary.wiley.com/doi/10.1111/bjh.12091. Accessed August 26, 2019.
  6. National Hemophilia Foundation. Facts about inhibitors. https://www.hemophilia.org/sites/default/files/document/files/Facts-About-Inhibitors.pdf. Published 2017. Accessed August 26, 2019.
  7. Testing for inhibitors. The Hemophilia, von Willebrand Disease & Platelet Disorders Handbook website. https://www.hog.org/handbook/article/4/17/testing-for-inhibitors. Accessed August 26, 2019.

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