Catch-up time for diagnosis and management of von Willebrand disease

While haemophilia is the most well-known inherited bleeding disorder, the commonest such disorder is in fact von Willebrand disease (vWD). Despite regional guidelines in countries such as the USA and UK, there has been no global agreement and endorsement from both the scientific and patient communities to drive forward better evidence-based treatment and care for those affected by the disorder. So the publication of the first-ever international guidelines for the diagnosis and management of von Willebrand disease is welcome.

The guidelines were jointly developed by the World Federation for Hemophilia (WFH), the American Society of Hematology, the International Society on Thrombosis and Haemostasis (ISTH) and the National Hemophilia Foundation. There are two parts –diagnosis and management – with a total of 23 recommendations [1,2]. Both are available online as a brief summary and with a detailed, fully referenced explanation of the evidence. The WFH has posted a video of a webinar in which the guidelines and their potential for advocacy are discussed. This document focuses on the most common forms of inherited VWD and refers readers to several other sources for more detailed information.

The guidelines are intended for health professionals and people with VWD. By contrast with many others, they use two classes of recommendation, defined in a novel way. A ‘strong’ recommendation indicates a course of action that most patients would want and that clinicians can expect most patients to follow, that policy makers can confidently adopt, and that researchers know are backed by evidence. A conditional recommendation – “the panel suggests…” – recognises that patients, clinicians and policymakers may make different choices and researchers may want stronger evidence. Many of these recommendations/suggestions are based on evidence of low certainty.

These are supplemented by good practice recommendations which are comparable with strong recommendations but ‘endorse interventions or practices that the guideline panel agreed have unequivocal net benefit yet may not be widely recognised or used’.

The complex diagnostic pathway is usefully summarised in an algorithm. Guidance covers the use of a bleeding assessment tool for screening, which tests to use to measure VWF activity and to determine subtypes, and reconsidering the diagnosis when VWF levels change. Values for VWF activity are suggested for Type 2 VWD but recommended for Type 1 VWD. The threshold VWF activity defining Type 1 VWD is clearer than in some other guidelines (a level of <0.30 IU/mL regardless of bleeding and a VWF level of 0.30 to 0.50 IU/mL for patients with abnormal bleeding) and the term ‘low VWF’ is avoided, both of which should reduce underdiagnosis.

All of the 12 recommendations on management are ‘suggestion’-strength only. Prophylaxis is an option for people with a history of severe and frequent bleeds. If desmopressin is an option, it is preferred to tranexamic acid provided a trial suggests benefit. Patients with VWD who need treatment with antiplatelet agents or anticoagulant therapy for cardiovascular disease should have it. After surgery, levels of both FVIII and VWF activity should be targeted, not only FVIII. The guidelines propose VWF activity levels to cover neuraxial anaesthesia and provide advice on using tranexamic acid to cover minor surgery and invasive procedures. Hormonal therapy or tranexamic acid are preferred to desmopressin to control heavy menstrual bleeding; after delivery, women should be offered tranexamic acid, especially if they have type 1 VWD or low VWF levels.

The management guidance is similar to older guidelines from the UK and the USA, with differences largely in the strength of evidence and inclusion of patient and family preferences when a clear treatment choice is lacking.

These new guidelines, while welcome, highlight the need for much more research into the diagnosis, treatment and management of vWD. The evidence presented in the guidelines, is often considered weak. There is a lack of good quality research in the area, particularly related to treatment and management options. The evidence required for improving care and management for those affected by or with vWD can be improved. Emerging evidence of the impact of living with von Willebrand’s, such as obstetric and gynaecological bleeding and musculo-skeletal complications, indicates that research should have a multi-disciplinary approach with a focus on improving quality of life through improving quality of care. We at Haemnet would like to see standards of care for all those with vWD, to include access to comprehensive multidisciplinary care as is accepted practice in haemophilia.

With the “Cinderella Study”, Haemnet is currently investigating the unmet needs for women and girls affected by bleeding disorders and a large number of the almost 300 participants have vWD. Abstracts from the study with initial findings will be presented in the Poster Section at next week’s EAHAD meeting.

References

1. James PD, Connell NT, Ameer B, et al. ASH ISTH NHF WFH 2021 guidelines on the diagnosis of von Willebrand disease. Blood Adv 2021;5:280-300. https://doi.org/10.1182/bloodadvances.2020003265
2. Connell NT, Flood VH, Brignardello-Petersen R, et al. ASH ISTH NHF WFH 2021 guidelines on the management of von Willebrand disease. Blood Adv 2021;5:301–325. https://doi.org/10.1182/bloodadvances.2020003264