• What is…
• Diagnosis

Inhibitors

In some patients who receive treatment with factor, the immune system reacts to proteins in the factor as if they were a harmful foreign substance. The immune system usually defends the body from viruses and bacteria. One way it does this is to make antibodies (inhibitors because they stop the factor from working). If a patient’s immune system starts to make these antibodies then injecting the usual factor replacement may not stop bleeding.

This makes bleeding harder to control so more intensive or alternative treatment may be needed to control bleeds.

On average 20-30 % of people on treatment for haemophilia A will develop an inhibitor at some point. Most inhibitors are temporary and they most often appear in the first year of treatment. Inhibitors in haemophilia B are much less common, with around 1-3 % of people on treatment developing an inhibitor.

When an inhibitor is detected, there are 2 aims to treatment:

1. Treating bleeds

   The choice of treatment will depend on the inhibitor type and level. Often bypassing agents are needed to control the bleeding. Bypassing agents work around the inhibitor and help the blood to clot.
   The haemophilia centre will advise on how to treat an individual’s bleeds. If you need more information please contact your local haemophilia centre.

2. Removing the inhibitor

   It is possible to get rid of inhibitors using a method called immune tolerance therapy (ITT).
   This involves waiting for the inhibitor level to fall then introducing daily injections of factor (while bleeds are treated with bypassing agents). Over time the immune system begins to recognize the clotting factor as not foreign and stops producing the antibodies.
   ITT may take a long time, from 6 to 24 months. ITT is successful in about 80% of cases.

This is a complex problem and any individual who develops an inhibitor will be cared for by a specialist comprehensive care centre. If you have any questions or want to know more please contact your local haemophilia centre for details.

Joint damage

If haemophilia is poorly controlled bleeding into joints can occur. This can cause damage to the cartilage (the soft spongy tissue in joints that acts as a shock absorber) as well as the synovium (a thin layer of tissue that lines the inside of the joint). Successive joint bleeds may cause more damage. The more damaged a joint is, the more vulnerable it is to internal bleeding. This in turn means the joint will become even more damaged and vulnerable to bleeding.

Joint damage is more common in older adults with severe haemophilia because preventative treatments were not available in the past.

Surgery can be used to treat joint damage. If the synovium is damaged, it can be removed so new synovium can grow in its place. If a joint is seriously damaged, it may be necessary to replace the whole joint with an artificial one, such as a hip replacement or knee replacement. If you would like more information on the treatment of joint problems talk to the team at your local haemophilia centre.

Blood borne infections

With treatment developments in the 1960s, many patients started to receive treatment with factor VIII and IX made from pools of plasma. Unfortunately these concentrates were not treated to inactivate viruses. This meant that users of the concentrate ran a high risk of being infected by blood borne infections.

Hepatitis B, hepatitis C and human immunodeficiency virus (HIV) were all discovered in the blood supply in the 1970s and early 1980s. Unfortunately a large number of individuals who infused plasma-derived factor concentrate were infected with these viruses.

Once tests became available for these viruses the blood donations were screened to reduce the risk of the infections.

Today, plasma-derived factor concentrates are highly purified and treated to inactivate viruses. Most patients in the UK receive recombinant FVIII, which is manufactured using genetically engineered cells that carry a human factor gene.

In the UK, people infected with hepatitis C through treatment with NHS blood or blood products (including factor concentrate) before 1991 may be entitled to compensation. See the EIBSS for more details.

Newer treatments for hepatitis C are currently being evaluated by NICE. If you would like more information please contact your local haemophilia centre.

Select content reproduced with permission from www.wfh.org

If you would like to know more about this or have any questions about the current treatments used please ask the staff at your local haemophilia centre or see the links below.