In this section we will provide more information on:
People with bleeding disorders are treated with what is called replacement therapy. This means that the missing clotting factor is infused in their body on a regular basis so that the clotting process can occur normally. Unfortunately, some people develop antibodies, called inhibitors, that neutralise the replacement clotting factor.
This means that the body induces an immune response to the treatment and therefore prevents the infused clotting factor from functioning normally. In this case, bleeds become very hard to control and can lead to permanent joint or muscle damage, making people with inhibitors disabled.
Treatment of inhibitors is the biggest challenge in haemophilia care today. It is possible to get rid of inhibitors using a technique called immune tolerance induction (ITT). However, this type of treatment requires specialised medical expertise, is expensive and takes a long time. Drugs called bypassing agents can be used to work around inhibitors and help blood clot.
In haemophilia, inhibitors occur more often in individuals with the severe form than those with moderate or mild haemophilia. It is estimated that approximately 30% of patients with haemophilia A and 1.5% to 3% of patients with haemophilia B develop inhibitors to factor VIII and factor IX concentrates, respectively. For rare bleeding disorders, figures are unclear due to the limited patient population and the lack of treatment.
Inhibitors typically occur in the first 75 exposures to the treatment, this is why it is important that people with bleeding disorders receive their first treatment under medical supervision in a treatment centre where the right medical facilities and expertise are available in case of inhibitor development or other allergic reactions. In fact, allergic reactions may amplify when treatment is given over time. Ideally, children and adults who are newly diagnosed with haemophilia should be tested regularly for inhibitors between the 1st and 50th days of treatment. Even after the 50th day of treatment, they should be checked at least twice a year until they have received 150-200 doses and at least once a year after that. Testing for inhibitors should also be done before any major surgery.
Some studies have shown that people who receive regular treatments with factor concentrates to prevent bleeds (prophylaxis or prophylactic treatment) have a lower chance of developing inhibitors in their lifetimes. Little is known about whether the type of factor concentrates (recombinant or plasma-derived) that is used plays a role, but there are ongoing studies to shed light on this matter.
Treatment options for people with inhibitors:
Immune tolerance induction therapy
Immune tolerance induction (ITI) therapy involves giving the person with inhibitors frequent doses of factor concentrates over several months, or sometimes years, to train the body to recognise the treatment product without reacting to it. This process is called tolerance induction. If a person plans to undergo immune tolerance induction therapy, but has not yet started, it is better not to use factor products to treat acute bleeding episodes because they are likely to provoke a rise in inhibitor titer.
Bypassing agents
Bypassing agents, such as activated prothrombin complex concentrates (APCC) and recombinant factor VIIa (rFVIIa), are used to treat acute bleeding in people with high titer inhibitors. However, these treatment products are expensive and not always available in every country.
Tranexamic acid
Tranexamic acid is an antifibrinolytic drug that can be given as an additional therapy in pill form or by injection to help stop blood clots from breaking down. It is particularly useful for bleeding that involves mucous membranes such as those in the nose or mouth. However, it should not be used in combination with APCCs.
Plasmapheresis
Plasmapheresis is a procedure that removes inhibitors from the person’s bloodstream. It is usually done when the inhibitor titer needs to be brought down quickly (for example, before major surgery or in cases of severe bleeding that are not well controlled with bypassing agents).
High-dose factor concentrates
Administering factor concentrates at higher doses and/or more frequent intervals is the preferred treatment for acute bleeding in low responders. The person’s factor level should be measured right after each infusion to make sure that target levels are reached. Continuous infusion may be useful. High-dose factor concentrate is also the preferred treatment option for acute bleeding in previous high responders with current low titer inhibitors — however, it is vital to take into account that the anamnestic response will get stronger within five to seven days, at which time treatment should be switched to bypassing agents.
The European Inhibitor Network (EIN) is a programme of the European Haemophilia Consortium (EHC) that is dedicated to people with haemophilia who have inhibitors, their families and caregivers from across Europe.
As you know, haemophilia is a rare disorder, but haemophilia with an additional diagnosis of inhibitors, further places the patients and their families into living with a rare disorder within a rare disorder. The number of patients diagnosed with inhibitors in each country is, thankfully, small, nevertheless this diagnosis brings a degree of stress and isolation due to a variety of reasons, e.g. lack of information among the patients and clinicians, scarcity of sufficient treatment, as well as social barriers caused by mobility and other issues.
We can bring those patients together on the European level, in larger numbers with the help of various support systems. Through EIN they have the opportunity to connect, share experiences, and build a community and support network on a European level.
Objectives
In implementation of programme and activities of the European Inhibitor Network, EHC is working closely together with its NMOs and the key partners in order to achieve the following objectives:
- Better understanding and prioritisation of the needs of PWI both at a community as well as at a policymaking level
- Establish European consensus in order to harmonise and ensure that we have optimum standards for the treatment and care of PWI
- Enable social and educational connections between PWI and between their caregivers to allow them to support and educate one another
- Ensure that PWI themselves are also active and effective at engaging directly with payers, policymakers and other authorities to advocate for optimum therapy and care.
Programme elements
An Inhibitor Working Group was established to work towards realisation of the objectives and implementation of the various elements of the programme. This working group consists of patients, parents, clinicians and other community members, as well as a staff member of the EHC to coordinate the programme. It has been and will continue to be essential to work in a close cooperation with all the NMOs of EHC, as well as to seek partnerships with the relevant partners.
There are three main European Inhibitor Network programme elements:
1. Establishment of European Standards of Treatment and care for PWITen complementary principles for the management of inhibitors in haemophilia have been developed and published, emphasizing the importance and benefits of a centralised, multidisciplinary, expert and holistic approach. These principles will serve as a benchmark to improve the multidisciplinary and practical management of patients with inhibitor. Implementation and adherence to each of these principles should have a major positive impact on the management and outcomes of patients developing an inhibitor.
In addition to the article published in Orphanet Journal of Rare Diseases , a video and a poster outlining these principles, are being produced to be used as advocacy tools by PWI.
EHC Inhibitor Summit 2016, 2017 & 2018
The purpose of the EHC Inhibitor Summit is to offer a special time and space for people with haemophilia who have inhibitors, their family members and caregivers to build a community, educate and empower themselves, and to help improve the quality of their lives. A very important aspect of the Summit is building the community, and finding support and understanding among people in a similar situation. Since the first Summit in 2016, more than 200 patients and their families from over 17 European countries have come together to share their experiences and learn from one another. The Summit has proved invaluable in creating a community for this isolated and rare group within the haemophilia population. The next EHC Inhibitor Summit is scheduled to take place in December 2018.
Inhibitor Ambassadors
This is a person, nominated by the EHC National Member Organisation or NMO. The main role of the Inhibitor Ambassador is to further strengthen the community of people with inhibitors and their caregivers in Europe by being the active link between the PWI in his/her country and the EIN on the European level, more actively involving the people with inhibitors within your society.
Chat Room & ASK THE EXPERT
An online platform for people with inhibitors has been developed ad a part of the EIN. It seeks to create an online community and facilitate exchange, support and education, enabling social and intellectual connections between PWI and between their respective caregivers and family members. The online community consists of 3 main segments, which are interlinked – understanding, learning and meeting. Information and articles are available about inhibitors and various aspects of living with inhibitors; a Chat Room is open to enable the discussions and exchange of experiences among the PWI; experts in haemophilia treatment and care are available each month to provide educational information to patients on various nominated topics.
To enable people with inhibitors, their caregivers and family members to engage with the relevant stakeholders to advocate for optimum therapy and care, the EHC has developed several tools. The EIN online platform provides specific educational material for each relevant stakeholder – patients, caregivers and NMOs on current management, treatment available for people with inhibitors and other issues such as physiotherapy and psychosocial issues. Series of good practices collected from the NMOs give an insight of support systems available for implementation, and the European Principles of Inhibitor Management set a benchmark that will enable improvement and help ensure that all inhibitor patients receive optimal treatment and care, regardless the country they live in.
Contacts
For more information please visit the EIN online platform or contact EHC Community Programmes Officer, Ms Kristine Jansone at [email protected]
Sponsors
The European Inhibitor Network is made possible thanks to an educational grants from Alnylam, Baxalta (now part of Shire) and Roche.
Jim is aged 66 and has Haemophilia A with a high titer inhibitor which he developed at age 14.
Maria Elisa Mancuso (MD, PhD) is a Haematologist and works as a Senior Haematology Consultant at the Center for Thrombosis and Haemorrhagic Diseases of IRCCS Humanitas Research Hospital in Rozzano, Milan, Italy. She is Adjunct Clinical Professor at Humanitas University. She obtained a post-degree in Clinical and Experimental Haematology and a PhD in Clinical Methodology. She is involved in clinical research and has published several original articles in peer-reviewed journals a The Lancet, Blood, Journal of Thrombosis and Haemostasis, Haematologica, Thrombosis and Haemostasis, British Journal of Haematology and Haemophilia. She is reviewer for several peer-reviewed journals and member of the Editorial Board of JTH. She is a member of several scientific societies (ISTH, WFH, ASH, EAHAD, SISET, AICE) and was a medical member of the Inhibitor Working Group of the European Hemophilia Consortium. She is co-chair of the ADVANCE Study Group. She has acted also as co-chair of the Scientific and Standardization Subcommittee of ISTH on FVIII, FIX and rare bleeding disorders. She has been involved as principal and co-investigator in several clinical trials, and she takes care of both children and adults with hemophilia and other congenital bleeding disorders with a specific scientific interest in novel therapies, prophylaxis, inhibitors, and chronic hepatitis C.
As a patient with factor II deficiency, the diagnostic and treatment of rare bleeding disorders is a matter dear to my heart. My motivation to participate in the work of the ERIN committee is to improve both diagnostic and treatment for patients with rare bleeding disorders across Europe.
Economist and financial expert by profession, executive coach and trainer by passion and haemophilia advocate by every drop of my blood through my son (who has severe haemophilia A with inhibitors). Bringing a good decade of practical experience from the corporate insurance world, laser focus, growth mindset and resilience from my own experience, offering you anything I can just do, in hope that together we can make life more fulfilled for those impacted by bleeding disorders.
Amy Owen-Wyard is a Registered Mental Health Nurse. With experience working with children, young people, their families and adults with severe and enduring mental health conditions. Amy was also involved in a service improvement to provide a holistic care approach for those in general hospitals to support both their mental and physical health, whilst sharing her expertise and knowledge in mental health with the wider multidisciplinary team.
