According to The Hemophilia Federation of America (HFA) approximately 30% of people with severe hemophilia A are affected by inhibitors at some point in their lives. An inhibitor usually occurs between the 5th and 50th infusion of factor concentrate, but in rare cases can also be developed later in life.
This can be challenging because inhibitors can create more problems like joint arthropathy, which adds to the overall cost of hemophilia.
Sheh-Li Chen, PharmD, BCOP researched the economic costs of hemophilia and how that impacts treatment and reported that, “costs rise substantially for patients with complications, such as HIV seropositivity, arthropathy, and/or development of inhibitors. Some estimates claim treatment costs as high as $1 million per year for these patients.”
Approximately 2-3% of people with hemophilia B develop inhibitors, as well. Although less common than people living with hemophilia A inhibitors, 50% of patients with hemophilia B inhibitors will develop a severe allergic reaction to their factor IX infusion therapy. HFA says this could be life threatening.
Inhibitors can create more challenges than just the severity of hemophilia of a patient. These challenges can create more risk factors to think about:
- age/number of exposures to factor product
- family history of an inhibitor
- race/ethnicity (people of African American and Hispanic descent are at a higher risk of developing an inhibitor)
- gene mutation (there are ongoing studies that indicate the type of genetic mutation one has may indicate a higher risk of inhibitor development)
- intensive factor therapy related to surgery or trauma
Who is the most at risk for an inhibitor?
The National Hemophilia Foundation states inhibitors most often develop during childhood, especially during the first 50 exposure days. People with hemophilia have the greatest risk for developing an inhibitor during childhood. The incidence of inhibitors is highest among those with severe hemophilia, followed by moderate and mild deficiency or moderately severe hemophilia. The risk of inhibitor development is higher if someone in the patient’s family also has an inhibitor, and is more frequent among African Americans.
What are the symptoms of an inhibitor?
Inhibitors destroy the infused factor concentrate, as well as the factor produced naturally by the body in people with mild and moderate hemophilia. A person who doesn’t have inhibitors will heal from injuries or feel better soon after the factor concentrate is infused. A person with an inhibitor does not get better after receiving a dose of factor that is appropriate for their weight.
How are inhibitors detected?
According to the CDC, they say that a blood test is need to diagnose an inhibitor. 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.1 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. Eligible individuals can receive free inhibitor testing at federally funded HTCs through the Community Counts Registry for Bleeding Disorders Surveillance.
Are inhibitors all the same?
No. HFA says that Inhibitors come in different degrees of severity. Inhibitors are measured in titer (the amount of inhibitors present in a person’s blood) and immune response strength (how the immune system responds to additional infusions of factor concentrate).
- Titer: The inhibitor titer is measured in Bethesda units (BU). This number represents the amount of inhibitors in the person’s body. Inhibitors are classified as follows:
- Low Titer – Amount in the blood is less than 5 BU. The number, and therefore strength, of the inhibitor is low. People with low titer inhibitors can sometimes continue to use factor VIII or factor IX products to treat bleeds; they just need a lot more of it. Low titer inhibitors can sometimes resolve on their own.
- High Titer – Amount of inhibitors found in the blood is greater than 5 BU. The number, and therefore strength of the inhibitor, is high. People with a high titer inhibitor get no benefit from factor VIII or factor IX, no matter how much they infuse.
- Anamnestic Response: Once an inhibitor is present, the strength with which the body reacts to further exposure of factor concentrate, also called anamnestic response, can further classify the inhibitor type.
- Low Responder – when people with low-responding inhibitors receive factor VIII or factor IX, the inhibitor titer does not rise. Because the titer stays low, they may be able to control bleeding by using larger quantities of those factor concentrates.
- High Responder – when people with high-responding inhibitors are exposed to factor VIII or factor IX the immune system quickly triggers even more inhibitor development.
HF Healthcare provides all of the products used to treat inhibitors and can create a manageable care plan that works in concert with your physician and insurance payer. We are here to guide you to a healthy future! Call today! 866.981.1171
1. Hay CR, DiMichele DM, International Immune Tolerance Study. The principal results of the International Immune Tolerance Study: a randomized dose comparison. Blood. 2012; 119(6):1335-1344.