What is an inhibitor?

Inhibitors are antibodies to Factor VIII or Factor IX. Antibodies are a protein made by the body in response to recognition of a substance within the body as foreign. Their role is to eliminate foreign substances from the body.

Inhibitor Facts

• Inhibitors interfere with infused factor concentrate.
  
• Bleeding continues despite treatment.
  
• Inhibitor development can occur at any time but most likely to develop in the early days of treatment.
  
• Most develop in the first 10-20 days of treatment with Factor VIII.

What is the percentage of individuals with an inhibitor?

15% to 35% of individuals with severe Factor VIII deficiency
-may be as high as 22%-52%
1% to 4% of individuals with severe Factor IX deficiency

Individuals most likely to develop an inhibitor are:

• Those affected with severe hemophilia.
• A family history of hemophilia and inhibitors.
• People of African-American or Hispanic descent.

Factor IX inhibitors pose special challenges.

What are the signs of inhibitor development?

Typically, there is a poor response to treatment.

• Higher doses of factor are needed
• More frequent dosing is required to stop the bleeding
• Treatment doesn’t work

If you notice a change in response to treatment, call your HTC immediately. You may need only a change in dose, but it could also be a sign of an inhibitor. Your HTC staff will direct you.

When should inhibitor levels be tested?

• During routine comprehensive evaluation
• Before surgery
• If regular doses of factor do not seem to work

What is the impact of an inhibitor?

Inhibitors may cause normal factor replacement to not work.
All surgeries in hemophilia require special planning with HTC. Treatment is more challenging.

If you suspect an inhibitor is developing, it is important to contact your HTC, as your treatment plan WILL change.

How are inhibitors detected?

A blood test is give known as a Bethesda Assay.
It measures the strength (titer) of Factor VIII or Factor IX Inhibitors. Inhibitors are measured in Bethesda-Units (BU)

The higher the BU, the stronger the inhibitor.
Each BU of inhibitor consumes a 50% level of factor
Normal is “0” or not detected.

What are the different kinds of inhibitors?

Low responding Inhibitor (<5BU)

1. Decrease the response to treatment
2. Increasing the dose may stop the bleeding
3. Amount of inhibitor does not go up when the patient is given
   Factor VIII or Factor IX.
4. Easier to manage

Treatment of bleeding in individuals with low-titer inhibitors often can be treated with higher doses of Factor VIII or Factor IX.

High responding Inhibitor (>5BU)

1. Inhibitor may increase after treatment with Factor VIII or Factor IX
2. Treatment depends on type of inhibitor, individual characteristics, location and severity of bleeding episode
3. More challenging to manage

How are bleeds managed for individuals with a high responding inhibitor?

• High doses of factor until inhibitor increases
• APCCs (Activated Prothrombin Complex Concentrates) such as:
  Feiba, Autoplex
• PCCs (Prothrombin Complex Concetrates) such as Konyne-80
• Recombinant VIIa

Can inhibitors be eliminated?

Immune Tolerance Therapy (ITT) is a treatment regimen intended to TRY to eliminate inhibitors so the person with hemophilia can resume the use of Factor VIII or Factor IX.

ITT requires frequent, regular infusions with Factor VIII or Factor IX.
There has been a 60%-80% success rate with ITT.
It may eliminate the inhibitor and enable treatment with Factor VIII or Factor IX.
There are several different treatment regiments or protocols.

What are the disadvantages to Immune Tolerance Therapy (ITT)?

• IV Access
• Time Intensive
• Cost

Support for patients with Inhibitors

FactorHealth’s ISEE (Inhibitor Support Education and Empowerment) Program. This program provides education specific to patients and families living with an inhibitor. Contact the Education Department at 1-866-322-3461 or visit www.factorhealth.com

www.hemophilia.org

www.novoseven.com