The Body’s Reaction to a Perceived Threat
Inhibitors are one of the most serious complications of hemophilia. Inhibitors are much more common in patients with hemophilia A than with hemophilia B. Over a patient’s lifetime, there is up to a 30% risk of developing an inhibitor if they have hemophilia A; in hemophilia B that risk is approximately 5%.
Inhibitors (also known as antibodies) occur when the body thinks the infused factor product is a threat. Producing an antibody to remove a specific threat is the body’s natural defense mechanism. The antibody which is called an inhibitor works by removing infused factor VIII or factor IX from the body very rapidly, before it has had to chance to help stop a bleed.
Once an inhibitor develops, treating a bleed becomes very complicated. In many cases a treatment plan will be developed to help the body not see factor as a threat or to tolerate the presence of factor. This treatment is called immune tolerance therapy (ITI).
In addition to ITI, a new treatment plan for bleeding episodes must be developed. Patients are either given high doses of factor or other factor products called bypassing agents. Bypassing products work to “by-pass” the impact of the inhibitor and help blood clotting to occur.
Very few clinicians and hospitals in the US are familiar with treating hemophilia patients who have developed inhibitors. The IHTC is the largest center in the US for diagnosing and treating these patients.
Our familiarity with this complication and our innovative and world-class treatment therapies mean that you or your child are in the best possible hands and will receive state of the art, personalized care.
How to Detect and Treat Inhibitors
In severe hemophilia, an inhibitor is most likely to develop when a child is young and starts receiving regular infusions of factor product. In mild or moderate hemophilia, it is more likely for a patient to develop an inhibitor following a major surgery or later in life due to their less frequent use of factor products.
Inhibitors can have a very negative effect on the health of a patient, as they make it hard to stop bleeding once it occurs. This may lead to an increased risk of joint damage, general ill health and risk of hospitalization or death.
It is very important to diagnose an inhibitor as early as possible and begin immune tolerance induction (ITI). In general, the earlier an inhibitor is detected, the easier the ITI therapy will be.
Contact the IHTC immediately if you or your child believes your factor product or prophylaxis regimen is not working as well as in the past. This is one of the earliest signs of an inhibitor.
Inhibitors are also found on screening laboratory evaluations, completed in clinic, often before symptoms occur. IHTC works with national partners such as the Centers for Disease Control and Prevention (CDC) to provide our patients with the most advanced monitoring tests.
IHTC’s expert staff diagnoses inhibitors and recommends all hemophilia patients are tested annually, while more frequent testing is recommended for patients who are young or at higher risk of developing an inhibitor.
“Resetting” the Immune System
If you or your child develops an inhibitor, the best course of action is to stop your body from producing more of the inhibitor. This is done using a comprehensive treatment plan known as immune tolerance induction (ITI).
In simple terms, ITI is an attempt to reset the immune system to tolerate what it currently perceives as a threat. This is done by regular infusion (typically once or twice daily) with large doses of factor product, possibly over a lengthy period of time. In some cases, such as in hemophilia B or in mild hemophilia, an immunosuppressant is also administered to help decrease the immune response.
When ITI is successful, you or your child can resume administering factor VIII or factor IX to control bleeds; in the meantime, other treatment options are available to control bleeding.
The success rate of ITI and the type of ITI protocol used depends on the type and severity of hemophilia. ITI has been used since the 1970s; however, very few providers have vast experience with this treatment. The IHTC has state of the art protocols to treat almost any type of inhibitor. In some cases, an initial round of ITI may not be successful. In these cases, there are almost always alternative protocols that can be attempted.
Bypassing Agent as Alternative Therapy
If you or your child develops an inhibitor and factor VIII or factor IX are no longer able to help you stop a bleed, the IHTC will prescribe an alternative therapy known as a bypassing agent. As the name suggests, this type of product can bypass the need to administer factor VIII or factor IX. There are two widely available bypassing agents: FEIBA and NovoSeven.
FEIBA® (also known as an activated prothrombin complex concentrate or PCC) is a plasma-derived product which contains a wide range of different clotting factors to help your body form a clot when needed.
NovoSeven® (also known as rFVIIa or activated recombinant factor seven) is a recombinant version of activated factor VII. Activated factor VII can jump start a different pathway in your body’s clotting mechanism, again bypassing the need for factor VIII or factor IX.
As with factor VIII and factor IX clotting concentrates, these products may be used as a prophylaxis therapy (for bleed prevention) or as an on-demand therapy (for bleed treatment).
In some cases, if you have low levels of an inhibitor (also known as a low titer or a low responding inhibitor) you may still be able to use factor VIII or factor IX products, but at higher doses.
IHTC physicians can discuss options for preventing or treating bleeds when you have an inhibitor. Some patients respond better to one product than the other, and some patients may have a negative to reaction to one of the products. IHTC will help you find out which product works best for you or your child.
Immune Tolerance Induction (ITI) with Prophylaxis
Patients on ITI may have ongoing bleeding issues and may also be placed on prophylaxis. The goal of this treatment is to infuse with a bypassing agent in addition to the factor for ITI several times per week to stop a bleeding pattern or prevent further complications.
This is a very individualized treatment plan developed for your particular situation and may change based on your response to ITI and your bleeding symptoms.
Hemlibra
Hemlibra is a medication used for the prophylactic treatment of patients with FVIII hemophilia with or without inhibitor. Hemlibra is a bi-specific antibody (can simultaneously bind to two antigen) that mimics the role of factor VIII in clotting.
Since Hemlibra is not actually factor VIII, the inhibitor does not work against it. Hemlibra is given as a tiny injection under the skin once weekly to prevent bleeding.
This medication is used for prevention only and should not be used to treat an active bleed, and it will only work in FVIII hemophilia and not FIX.
Call the IHTC if you have questions or concerns about inhibitor development.