Age plays a crucial role in diagnosis of von Willebrand disease, says RCSI research

Reference: February 2024 | Issue 2 | Vol 10 | Page 47

Findings from a recent study by the Royal College of Surgeons Ireland (RCSI) University of Medicine and Health Sciences, in collaboration with the National Coagulation Centre at St James’s Hospital, Dublin, and Erasmus University Medical Centre, Rotterdam, have shown that the age at which a person is tested for von Willebrand disease (VWD) significantly affects their diagnosis.

The research is anticipated to have substantial implications for future VWD classification criteria, as well as care provision. The results may also contribute to resolving the ongoing debate regarding the type 1 VWD definition.

The common inherited bleeding disorder is generally characterised by quantitative deficiencies of von Willebrand factor (VWF), with levels <30IU/dL considered type 1 VWD, and significant bleeding accompanied by VWF levels between 30-to-50IU/dL being diagnosed as low VWF. Correct diagnosis of VWD is crucial as it dictates and determines subsequent treatment decisions, however, rates of misdiagnosis and underdiagnosis remain high.

Approximately 4,900 people in Ireland are affected by VWD, but only a third of those have actually received a diagnosis, according to the Irish Haemophilia Society.

Methodology and results

The study sought to investigate the relationship between type 1 VWD and low VWF in the context of age. Combining datasets from two national cohort studies in Ireland and the Netherlands – 162 patients with low VWF from the Low VWF in Ireland Cohort (LoVIC) and 403 patients with type 1 VWD from the Willebrand in the Netherlands (WiN) studies – the researchers assessed the relationship between the timing of diagnostic testing and the assigned subtype of VWD.

The study was led by Dr Ferdows Atiq and Prof James O’Donnell, RCSI School of Pharmacy and Biomolecular Sciences, and was published in Blood journal.

In 47 per cent of people with type 1 VWD, VWF levels remained <30IU/dL, regardless of increasing age. However, investigators found that VWF levels increased into the low VWF range (30-50IU/dL) in 30 per cent of patients, and normalised (>50IU/dL) in 23 per cent of WiN patients. Of particular note, absolute VWF antigen (VWF:Ag) levels and increase of VWF:Ag per year overlapped between low VWF and normalised in WiN subjects.

A multiple regression analysis demonstrated that VWF:Ag levels in the LoVIC cohort and normalised patients in the WiN cohort would not have differed had they been diagnosed at the same age.

Researchers concluded that the findings “demonstrate that low VWF does not constitute a discrete clinical or pathological entity”, and that instead, is “part of an age-dependent type 1 VWD evolving phenotype”. This may offer insight to address ongoing challenges around the misdiagnosis of VWD, as well as potentially reducing the risk of bleeding complications associated with the disorder.