Inhibitors are the body’s way of fighting off what it sees as a foreign agent. This means that as soon as the factor concentrate is infused, it is eliminated.
This is similar to what happens when a person receives a transplanted organ. The body’s immune system sees the organ as foreign and tries to reject it. People who receive transplanted organs need to take drugs to stop this from happening.
In hemophiliacs with inhibitors to factor concentrates, the rejection starts to happen as soon as the blood product is infused. This means that the factor concentrate is destroyed before it can stop the bleeding.
This is a very serious complication of hemophilia because factor concentrates are no longer effective. Treatment for bleeding just does not work. Hemophiliacs with inhibitors are at risk for crippling from bleeding into their joints. They can die from serious internal bleeding.
Inhibitors also affect about 1 in 50 people with mild or moderate hemophilia A. These inhibitors usually develop during adulthood. They not only destroy factor VIII concentrates infused, but they also destroy the body’s own factor VIII. As a result, mild and moderate hemophiliacs become severe.
Fortunately, in 2 out of 3 of cases the inhibitors disappear on their own, or with treatment, within, on average, 9 months. For the others, the inhibitors persist and are a serious problem.
In hemophilia B, inhibitors are much rarer. They affect about 1 in 100 people. In most cases these inhibitors develop after the first infusions of factor IX concentrate. Unfortunately, inhibitors in people with hemophilia B can be extremely serious because they can be accompanied by allergic reactions if factor IX is infused.
No, inhibitors come in different degrees of severity. Some people are said to be ‘low responders’. This means that the inhibitors are present at low levels (or low titers). They work much more slowly to eliminate the infused factor concentrate.
Others are said to be ‘high responders’. Their inhibitors are present at high levels and respond very quickly to the infusion of factor concentrates. As a result, the factor concentrates infused can be rapidly neutralized.
Inhibitors can vary in severity in the same person. At certain times, a person’s inhibitor can be very active; at other times it almost disappears.
Doctors do not know exactly why inhibitors develop in some hemophiliacs and not in others. They think there are 2 possible causes.
- The first possible cause is environmental. This is external to the hemophiliac. Doctors think that something in the factor concentrate triggers the body’s immune system to react. For this reason, many doctors who treat hemophiliacs prefer to switch concentrate brands as rarely as possible. If a product is working well, and has not caused inhibitors to develop, doctors won’t recommend a switch to a different product unless there is a very good reason.
- The second possible cause is genetic. Some hemophiliacs with a certain type of mutation of their factor VIII gene may be more prone to developing inhibitors. This explains why development of inhibitors sometimes runs in a family. Family members, of course, share the same gene mutation. This genetic cause of inhibitor development is also very possible in hemophilia B.
Inhibitors to factor VIII also develop in people who do not have the genetically transmitted forms of hemophilia. This is called acquired hemophilia, because it starts after birth, sometimes even in old age.
Acquired hemophilia is a disorder not present at birth, or not inherited like in hemophilia. The person’s immune system gets confused and starts attacking and destroying one of the clotting factors. Factor eight (FVIII) is almost always the target. The incidence is at least 1 to 1.5 cases per million people per year. It develops suddenly :
- after pregnancy
- after surgery
- after an accident
- after cancer
- after taking certain antibiotics
- for no apparent reason
Thankfully, the antibodies, or inhibitors, can be controlled or stopped with treatment in most cases. The person’s blood will again clot normally.
Doctors have 25 years of experience in helping people with hemophilia A get rid of their inhibitors. The different treatments are called immune tolerance therapy (ITT). Their goal is to get the body, and its immune system, used to the infusion of factor VIII so that it no longer rejects it.
Different protocols of ITT have been found successful. All the therapies include high doses of factor VIII for long periods.
These therapies last anywhere up to 36 months. They are successful with 2 out of 3 people with severe hemophilia A.
‘Low responders’ (people with low-level inhibitors) have a greater chance of success with ITT than high responders (people with high-level inhibitors).
Doctors have much less experience with immune tolerance therapy in hemophilia B. This is because the number of people with hemophilia B and inhibitors is very small.
Unfortunately, ITT seems to work less well with these people. What’s more, many hemophilia B patients with inhibitors have severe allergic reactions to the continued infusion of factor IX concentrates. This can make ITT a risky therapy.
Some hemophiliacs are not helped by immune tolerance therapy. They continue to have high levels of inhibitors which eliminate the normal factor VIII and IX concentrates infused. They need other kinds of treatment which do not eliminate the inhibitor but rather are aimed at stopping bleeding.
People with severe hemophilia A can receive:
- activated prothrombin complex concentrate (called FEIBA®VH in Canada)
- recombinant factor VIIa (called Niastase® in Canada).
People with mild or moderate hemophilia A can receive:
- activated prothrombin complex concentrate
- recombinant factor VIIa
People with hemophilia B can receive:
- recombinant factor VIIa.