Brandee, diagnosed at 12 years old with von Willebrand’s Disease (https://www.cdc.gov/ncbddd/vwd/stories.html#brandee)
Brandee, a 34-year-old woman, learned she had von Willebrand disease (VWD) type 3 at age 12, after experiencing extremely heavy periods. According to Brandee, when she started to menstruate, it never stopped.
“It was extremely heavy, so my parents took me to my paediatrician, and she ran a bunch of tests and said that she was going to have to refer me to a haematologist because she thought I had VWD, which I did. It was a surprise.”
Von Willebrand disease is one of a number of bleeding disorders. Haemophilia carriers and women with bleeding disorders (WwBD) often experience menorrhagia, bleeding following dentistry, surgery, injury, or childbirth. Symptoms are easily treated leading to full and active lives. Nevertheless, some girls and women suffer with abnormal bleeding for many years before diagnosis.
There is an underestimation of bleeding and late diagnosis in WwBD. In her presentation during 2021 EAHAD, Dr Roseline D’Oiron (Clinician Investigator and Associate Director at the Reference Centre for Haemophilia and Other Congenital Rare Bleeding Disorders, Congenital Platelets Disorders, and von Willebrand Disease at Bicêtre Hospital AP-HP – University Paris XI) supported the increasing awareness of disparities between genders when it comes to access to treatment and diagnosis of bleeding disorders in women and girls. She presented US registry data that compares diagnosis age between boys and girls with haemophilia, confirming the following delay in diagnosis for females - 6.5 months delay for severe haemophilia and 39 months for moderate haemophilia. By presenting comparable data from Belgium and France, Roseline confirmed that late diagnosis of bleeding disorders in women is a global issue.
Early diagnosis in WwBD is important. Heavy menstrual bleeding may not be recognised in girls because all the women in the same family may be having the same symptoms and therefore are not aware that what they are experiencing is abnormal. Abnormal bleeding will lead to pain, tiredness and consequent reduced quality of life and impairment in activities of daily living such as participation in sports activities. There may also be complications due to anaemia following substantial chronic blood loss.
Real World Evidence, including studies to characterise the burden of late diagnosis in WwBD, can play an important role in building a compelling evidence base, from which investment in clinical education can be improved, leading to the necessary changes in clinical practice. At EAHAD, Dr D’Oiron proposed practical improvement to clinical practice can include,
- Conceptualisation of experience though family history of bleeding
- Characterisation of the intensity of bleeding symptoms
- Characterisation of the impact on identity and quality of life
- Reduction of uncertainty surrounding diagnosis, including recognising women with bleeding disorders and differentiating from normal and abnormal bleeding symptoms
- Improve opportunity and output from open discussion with family members and peers
- Improve the likelihood of appropriate referral to haematologists
These practical suggestions for improvement in diagnosis for WwBD provide an early framework for the development of research questions that RWE studies can address. The suggestions also describe the desirable shape of any resulting evidence and the way in which advocacy work can be planned once evidence is available.
Along with research that addresses clinical reform and the way in which women are currently supported with information, support services and grass roots awareness are also important to improve understanding of what improvements can be informed by patient-reported data. Information and patient group service design can also be stimulated by real world evidence, particularly when employed in advocacy for patient-led improvement.
In her paper published in 2013, Kate Khair (Head of Clinical Research at HCD Economics, past Chair of the nurses committee of the WFH, founding Trustee of Haemnet [a haemophilia education and research charity], vice chair of the board of trustees of the Haemopilia Society and chair of the Women’s Bleeding Disorders Sub-committee) reported on the results from a study conducted among WwBD.
The study explored the experiences of girls and young women (aged 9-34 years) with bleeding disorders by means of focus groups which consisted of moderated discussion addressing specific aspects of bleeding, management, and coping strategies. Subsequently, these issues were explored further though a paper-based questionnaire distributed via five specialist haemophilia centres in the UK. The study suggested that young WwBD who are managed at haemophilia centres receive appropriate care and feel well supported. However, although the clinic-based literature available to these women is "fit for purpose", it does not fully address the perceived needs specifically regarding sex, menorrhagia, conception and childbirth, the Pill, tattoos/piercings and so on, leading many to turn to other information sources.
Important ground-breaking steps are being taken, but there is a compelling need for a more capillary network of initiatives through local patient representative groups, action and coordination around Europe and the world, in order to re-educate clinicians and change diagnosis-treatment paradigm.
There are a number of patient-led initiatives led by the volunteer Haemophilia community. These include the European Haemophilia Consortium ‘Women and Bleeding Disorders Committee’, at the European level, which has been officially operating since 2018, raising awareness and recognition to provide support and education about and for women with bleeding disorders. In a recently published survey-based study, the EHC has gathered data on the conditions and unmet need of WwBD around Europe. Additionally, extremely useful educational material is available on the website along with a “diagnostic quiz” which may help potentially affected women to identify early concerns.
National Organisations around Europe have their own initiatives as well. The UK haemophilia society, for example has its very own ‘Women’s Bleeding Disorders Sub-Committee’, operating at the national level to raise awareness, identify issues related to diagnosis and to ensure girls and women with bleeding disorders have equitable access to treatment of their bleeding disorders.
“Girls and women with bleeding disorders are underrepresented in haemophilia centres yet experience regular bleeding associated with periods and childbirth as well as following trauma and surgery. We hope that the recent publicity by global haemophilia organisations along with our Talking Red programme will address this inequitable care”
Kate Khair – Vice-chair of the UK Haemophilia Society trustee board and chair of the UK Haemophilia Society Women’s Bleeding Disorders Sub-committee
At the national level, the Italian haemophilia society, FedEmo, is active in providing information and support to couples on pre-implantation genetic diagnosis and medically assisted procreation. Support to WwBD in achieving appropriate and timely diagnosis and sufficient care is crucial. And to that end, FedEmo, has laid some important foundations with the success of “Finestra Rosa” (Pink Window), a project that focused on the psychosocial impact of haemophilia on women (carriers or carers), creating a national support group as well as a regional spin-off group (in the second edition of the project), focusing on the broader impact of chronic bleeding disorders on men and women. “Finestra Rosa”, in fact, provided the foundations and the insight to involve the community and develop steps together, to tackle the issues that WwBD face as members of the bleeding disorders community.
 Khair K, Holland M, Pollard D. The experience of girls and young women with inherited bleeding disorders. Haemophilia. 2013 Sep;19(5):e276-81. doi: 10.1111/hae.12155. Epub 2013 Apr 22. PMID: 23607927.
 Noone D, Skouw-Rasmussen N, Lavin M, van Galen KPM, Kadir RA. Barriers and challenges faced by women with congenital bleeding disorders in Europe: Results of a patient survey conducted by the European Haemophilia Consortium. Haemophilia. 2019 May;25(3):468-474. doi: 10.1111/hae.13722. Epub 2019 Apr 29. PMID: 31034126.