Female doctor gestures while talking to the young adult female patient about her symptoms

Age Affects Von Willebrand Disease Diagnosis, Study Reveals

The findings could help further define VWD and address current challenges in treatment.
Author: By Matt Morgan

The age that a person is first tested for von Willebrand disease (VWD) greatly affects the diagnosis and subsequent treatment, according to a study by researchers in Ireland and the Netherlands that was published in the April 2024 journal Blood. Based on their findings, the study authors recommend a change in the way the mildest forms of the disease are classified, which ultimately should help guide how it is managed.

The most common inheritable bleeding disorder, von Willebrand disease affects about 1% of the U.S. population, or about 3.2 million people. It results when the blood doesn’t have enough or an abnormal function of a certain protein, called von Willebrand factor, to clot properly.

Type 1 is the most common and mildest form of VWD. It is diagnosed when blood concentrations of von Willebrand factor are less than 30 IU/dL (international units per deciliter).

According to the research, there is considerable debate on how to define mild-to-moderate forms of von Willebrand disease.

The consensus among bleeding disorders experts has been that people with von Willebrand factor levels of 30–50 IU/dL should be classified as having low VWF and not type 1.

Recently, however, a panel of bleeding disorders societies and advocacy groups — which included the National Bleeding Disorders Foundation — strongly recommended that people with von Willebrand factor levels of 30–50 IU/dL and a significant bleeding history should be diagnosed with type 1 von Willebrand disease.

The researchers argue that age, rather than a threshold level of factor, is a key to defining the mildest forms of the disease and improving its diagnosis and treatment.

Important Findings from the Study

“We specifically investigated the critical question of whether low VWF is indeed a discrete clinical entity or whether it is instead part of an age-dependent type 1 VWD evolving phenotype,” the researchers write.

By looking at two national studies of more than 500 patients in Ireland and the Netherlands, the researchers determined that von Willebrand factor levels are age-dependent.

Their data highlight the fact that for many people, the diagnosis will depend upon the age at first testing, and “first VWF testing is only a snapshot taken at a single time point on a progressive age-dependent gradient,” the researchers write.

“Importantly, recent studies have demonstrated that there is often a major delay to VWD diagnosis, notably in women with heavy menstrual bleeding,” they write. “Consequently, many of these patients do not have plasma VWF assessment until they are aged 20 to 30 years. Our findings suggest that had these individuals undergone testing earlier in life, their plasma VWF levels would have been <30 IU/dL in many cases and, therefore, would have led to a type 1 VWD diagnosis.”

Ferdows Atiq, M.D., MSc, Ph.D., a senior research fellow with RCSI University of Medicine and Health Sciences in Dublin and the lead author of the study, spoke to HemAware about what the study findings mean for people with mild von Willebrand disease and the health care community.

Recommendations for Diagnosis, Treatment

“All patients with von Willebrand factor levels 30–50 IU/dL with an increased bleeding phenotype should be diagnosed with type 1 von Willebrand disease,” Atiq says.

Atiq also makes this recommendation for clinicians: “Be aware that patients referred at an older age with borderline von Willebrand factor levels around 50 IU/dL, who exhibit an increased bleeding phenotype, might have had lower von Willebrand factor levels (<50 IU/dL) if they had been assessed a few years earlier.”

As a result, if older people with borderline von Willebrand factor levels around 50 IU/dL have a bleeding history, Atiq tells HemAware that “they should be managed similarly to patients with von Willebrand factor levels between 30–50 IU/dL, considering potential changes in von Willebrand factor levels that could have occurred with age.”

Because von Willebrand factor levels can increase with age for some people, Atiq says that anyone with von Willebrand disease should have their VWF levels tested at least once later in life to provide a baseline for their factor levels.

This baseline is important because readings taken during severe bleeding episodes or surgery may not be reliable. “It is known that during acute stress,” Atiq says, “von Willebrand factor levels can temporarily increase and give an inaccurately high value.”

If you have type 1 von Willebrand disease, knowing whether you have low von Willebrand factor levels throughout your life, or a gradual increase in factor levels as you age, can help you in your treatment, Atiq says.

“If your von Willebrand factor levels have for instance normalized to above 100 IU/dL,” he says, “you might benefit more from treatments not involving von Willebrand factor, rather than from receiving desmopressin or von Willebrand factor concentrates, in case of bleeding episodes.”