EHC meeting on von Willebrands raises important questions
Yesterday (16.06.14) the European Haemophilia Consortium (EHC) held one of their regular Round Table meetings. These events are a fantastic opportunity for healthcare professionals, patients, patient organisations and pharmaceutical companies from across Europe to come together and discuss bleeding disorders. The topic for yesterday’s meeting was von Willebrands Disease (vWD)
The event was opened by Prof Paul Giangrande (Oxford University Hospital), who raised the question of whether it really was appropriate to refer to vWD as a disease. He wondered if a term like “deficiency” or “disorder” might be more appropriate. He felt that too often physical explanations for menorrhagia (abnormally heavy bleeding at menstruation) were looked for before a bleeding disorder was considered. He also thought that patient organisations had an important role to play in raising awareness to tackle that problem.
The first presentation highlighted that globally Haemophilia is under-diagnosed but that is even more true for vWD. Inside Europe there is quite a large range between places like Italy and France which report quite low levels of vWD and places like the UK where more people have been diagnosed. During the discussion this was partly explained by the down sides of having a diagnosis, especially if you aren’t experiencing bleeding problems and live in a country with a insurance based healthcare system, It might be the case that just by being diagnoses you insurance premiums go up even if you don’t need treatment. In several countries you would only be diagnosed with vWD if you fulfil two of these three criteria:
- Levels of less than 30.
- You have bleeding problems.
- You have a family history of vWD.
The most moving part of the meeting was hearing from Baiba Ziemele (The Latvian Haemophilia Society). Baiba told us that when she was growing up Latvia was part of the USSR. Her father knew that he had a bleeding disorder but didn’t know what it was called or that it could be passed on to his children. Even today she and her family don’t know what type of vWD they have and she has been told the laboratory services at the hospital don’t have enough people to complete the diagnosis project she has been working on with them. She explains how she has taken decisions in her life to reduce her exposure to problems from her bleeding disorder. That choice effects everything from shaving her legs through to her decision not to have children. She told how her sister bravely decided to have a child but that their simply wasn’t the expertise to support her and she had a very difficult experience. As a patient Baiba has some simple requests. She wants to know what type of vWD she has; she wanted doctors who know more about her condition than she does; and she wants them to be able to help her when she has bleeding problems.
The next presentation was also extremely powerful. Dr Susan Halimeh (Gerinnungszentum Rhein-Ruht) gave a presentation about the benefits of prophylaxis treatment for vWD. She highlighted that there weren’t clear guidelines for how much treatment was suitable for von Willebrands but that the benefits of treatment were impressive. During the discussion on this subject she, and Helen Campbell from the UK, argued that monthly menorrhagia is at least as good a justification for using a prophylaxis treatment regime and getting two or three joint bleeds would be for a man with Haemophilia. Women should not be expected to live with menorrhagia when there is a treatment solution. The discussion also recognised that it can be hard but not impossible for clinicians to make the case for the product needed for putting some with vWD on prophylaxis.
Prof Pier Mannuccio Mannucci (Hospital Ca’ Granda Foundation) discussed the controversial debate over the use of plasma derived or recombinant projects. He acknowledged the important role that von Willebrand Factor (vWF) has in both Gastrointestinal (GI) bleeds and menorrhagia. He felt that, where it works, Desmopressin (DDAVP) should be the treatment of choice as it avoids the need for clotting Factor and is cost effective. He felt that too often Factor products are used when DDAVP could be used. He demonstrated that most of the current, plasma derived, contain as much Factor VIII (FVIII) as vWF. The arrival of new higher concentration products such as Wilfactin or Recombinate will allow clinicans to look at whether FVIII is needed to effectively treat vWD. He told the meeting that FVIII often has a long half life in people with vWD. this means there is a danger of over-treating (peaking) FVIII when people with vWD get a lot of treatment. He thought that this could increase the risk of Deep Vein Thrombosis (DVT) and wondered if the new products could be used to avoid that. Looking to the future it was his opinion that vWD was not a good candidate condition for gene therapy.
Dr Carmen Escuriola-Ettingshausen’s (Hämophilie-Zentrums Rhein Main) presentation turned the meeting to consider the role of vWF in inhibitors. Inhibitors are the biggest current challenge in the treatment of Haemophilia. There is an ongoing debate on the vexed question of whether the likelihood of developing an inhibitor is higher with recombinant projects than with plasma derived products. Problems with the studies which have been carried out so far mean that there isn’t enough data to make a definitive statement on the issue. Therefore a new study, called the SIPPET Study, is currently being carried out. Similarly, there is a lack of validated evidence about whether using products with or without vWF has an effect on inhibitor rates. The experience in Germany where switching away from a product containing vWF to one without led to a reduction in the success of Immune Tolerance Therapy (ITT) suggests that vWF might have a role. The RESIST Study is investigating this question. With no firm evidence that one type of product is better than another there is still plenty of work to do. Staying on the topic of inhibitors we hear from Dr Srini V Kaveri (INSERM, Centre de Recherche des Cordeliers) about the role of immunology in inhibitors. He explained that if your immune system has produced an antigen to FVIII then it was made by your B Cells on instructions from your T Cells after it was presented to them as a potential threat. This means that there a lots of opportunities to use these processes to tackle the question of inhibitor development or to assist with producing tolerance.
The finals session was given by Dr Augusto B Federici (University of Milan) and looked at Acquired von Willebrands Disease (AvWD). With many aspects of the conditions progress on vWD is ten to fifteen years behind progress in Haemophilia and this is true for Acquired Haemophilia and AvWD. This is exasperated by the fact that there isn’t one single mechanism for AvWD. There is also a need for a good assay (test) when looking for an inhibitor in relation to AvWD. Dr Federici is currently working on setting up an Interactive Registry on AvWD which would be a valuable resource for tackling some of the challenges in this area.
The meeting ended with an open discussion. Liz Carroll from The Haemophilia Society (UK) updated on their Talking Red awareness raising campaign. Many of the women with vWD at the meeting spoke about their own experiences. Prof Giangrande asked if they had personal preferences on the recombinant vs plasma derived debate. There were a range of responses ranging from only being comfortable with recombinant to only wanting to be treated with plasma derived. Helen Campbell from the UK summed it up well saying that although she shared the concerns of many people with Haemophilia about plasma derived products she would take whatever worked best for her. She also stress that smaller volumes would make a big difference.
The next event will be in December and look at the role of National Haemophilia Committees.