Although they outnumber people with hemophilia by a large margin, those with von Willebrand disease (VWD) feel practically invisible at times. Some feel stigmatized, others’ symptoms are dismissed by untrained providers, and still others deal with untreated problems and pain.
To raise awareness of VWD and improve patients’ access to care, the National Hemophilia Foundation (NHF) convened a summit in Washington, DC, on November 21, 2014. A background paper prepared by the Lewin Group, a national healthcare consulting firm, identified challenges and opportunities for addressing the needs of the people with VWD.
The Lewin background paper was shared with key representatives from the bleeding disorders community who attended this summit. Participants included people with VWD, hemophilia treatment center providers, NHF staff, pharmaceutical industry employees and healthcare payers. In addition, there were representatives from several federal agencies, including the Centers for Disease Control and Prevention, the Food and Drug Administration, the Maternal and Child Health Bureau, and the National Heart, Lung, and Blood Institute (NHLBI).
Here are some of the highlights from the Lewin Group’s background paper:
Prevalence of VWD
Studies disagree dramatically on the prevalence of VWD, according to the report. “When based on the numbers of symptomatic people who are seen at specialized health centers for treating blood disorders, the reported estimate prevalence is roughly 23–110 per million population (i.e., 0.0023%–0.01%). However, when based on studies that screened populations for bleeding symptoms, low levels of von Willebrand factor, and similarly affected family members, the reported estimate prevalence is much higher, at roughly 0.6%–1.3% (i.e., 6,000–13,000 per million).”
In a table showing the distribution of age, race and sex of people with VWD from the CDC’s Universal Data Collection (UDC) Program from 2005–2009, women accounted for 60.5% of enrollees; men accounted for 39.5%. The paper concluded: “The discrepancies across studies in estimates of people within each type of VWD call attention to the need for more information on the relationship between VWF levels and clinical symptoms of bleeding episodes.”
The distribution of patients with VWD enrolled at hemophilia treatment centers (HTCs) and captured by the UDC was comparable to data from the Hemophilia Data Set (HDS), a data registry compiled by the HTCs.
The UDC revealed 83% were type 1; 11% were type 2 and 6% were type 3. The HDS showed 85%, 13% and 3%, respectively.
While the mutations causing types 2 and 3 are documented, those for type 1 are not, said the report. Further, research from sizable populations of patients with VWD show that there are more than 100 mutations for type 1 patients. An estimated 15% have multiple mutations.
In addition, a patient’s phenotype—symptoms and bleeding patterns—varies widely in VWD. Levels of von Willebrand factor (VWF) and bleeding don’t necessarily correspond. This complicates diagnosis, according to the paper. “Indeed, the rate of spontaneous bleeding may be low even in patients with severe deficiency, at about the level experienced by patients with moderate hemophilia.”
Diagnosis and reporting
Diagnosis of VWD is not straightforward, especially for those with type 1, or people with low levels of VWF and mild bleeding. Further, VWF levels can fluctuate in response to age, exercise, pregnancy or stress, skewing test results.
Another confounding factor is blood type. VWF levels in people with type O blood are normally lower compared with other blood types.
Patients themselves often underreport their symptoms. Women don’t disclose their menorrhagia, heavy menstrual bleeding, because of fear of stigma or lack of awareness that it could be the symptom of a bleeding disorder. Further, there is no consensus among physicians on whether or in what specific circumstances VWD testing should be a standard screening tool to determine the underlying cause of menorrhagia.
Further, diagnosing VWD in men is tricky. “VWD is typically unobserved in males except in cases of life-threatening bleeding events,” stated the report. Opportunities to diagnose men with VWD are missed because if their symptoms are mild to moderate, they can be dismissed, ignored or attributed to other causes.
Compounding the problem, most primary care physicians and other providers do not see patients with bleeding disorders and are not trained to recognize the symptoms of VWD. Their unfamiliarity with testing protocols leads to even more missed diagnoses, said the report.
The Lewin paper mentioned the use of bleeding scores (BS) to identify people whose risk of severe bleeds could warrant on-demand or even prophylactic therapy, regardless of their VWD type. The report stated: “The treatment approach for VWD should be personalized for each patient, depending on the type and severity of VWD as well as the nature and site of bleeding.”
Clinical practice guidelines
The report mentioned the use in the US of the NHLBI practice guidelines for VWD published in 2008. Although the guidelines provide detailed information on diagnostic recommendations, lab testing, making a diagnosis and management of VWD, they do not include “psychosocial issues or care coordination/delivery issues involving HTCs.” Further, the NHLBI acknowledges that the guidelines need to be updated.
Assessment of care
Studio-Annika/ThinkstockStatistics from the HDS show that from 1996–2010, there was a 148% increase in the number of patients with VWD using HTC services. Their numbers nearly tripled, from 5,326 to 13,239. “The increase in VWD patients, particularly among females, was the largest source of growth of HTCs during this time,” the report stated. Not surprisingly, of the women and girls seen at HTCs in 2010, 80% had VWD.
How women and girls feel about the care received at HTCs was also documented. In anecdotal reports, patients with VWD felt their care was insufficient and that providers treated them as lower in priority than their patients with hemophilia.
As older hematologists retire and other newly trained physicians are drawn more to careers in oncology than hematology, patients may experience a shortage of bleeding disorder specialists in the future. This trend could further affect the care of patients with VWD, and research and development for all bleeding disorders, said the report.
Psychosocial concerns of people with VWD are not well documented in the literature. Most of it is anecdotal and collected from women. Those with VWD report diminished health-related quality of life, specifically in terms of emotion, cognition and pain. Among women 18–25, menorrhagia disrupted their daily lives, including physical activities and sports, social events, and school and work.
The mistaken notion that VWD is a women’s disease stigmatizes men and leads to underdiagnosis, said the report.
Patients express difficulty discussing VWD-related challenges with their providers. “This strongly suggests that provider education and training are critical to ensuring that patients receive the range of care needed by people with VWD to achieve and maintain their health and quality of life,” the paper stated.
UDC data from 2005–2009 showed that 63.4% of patients with VWD had commercial insurance, 22.4% had Medicaid and 5.3% were covered by Medicare. Increased costs for infused factor products have prompted payers to resort to “using various forms of utilization management and increased contracting with preferred distribution providers.”
The Lewin report stated that there is a growing need for more studies on VWD alone, not in combination with hemophilia, and for systematic evidence reviews, not simply expert consensus, when it comes to management guidelines. “There is a dearth of comprehensive information about the pathophysiology, epidemiology, treatment, and psychosocial effects of VWD,” the report stated.
The paper concluded with 10 areas of focus for “stakeholders committed to improving care for people with VWD”:
1. Recognize and address stigma, apathy and clinical marginalization of people with VWD, including the respective needs of children and adults
2. Improve screening and diagnostic protocols for and classification of VWD, supported by further research on their clinical utility as needed
3. Improve quality and standardization of laboratory testing for VWD
4. Develop new or updated clinical practice guidelines for VWD, including psychosocial and healthcare delivery aspects, as well as clinical aspects
5. Improve education and training of primary care clinicians and gynecologists in VWD to improve their awareness, diagnosis and management of VWD, including more informative and supportive interaction with patients
6. Improve HTC protocols for recognition of and focus on VWD, including comprehensive care of VWD distinct from other bleeding disorders
7. Motivate and collaborate with industry for continued new product development and refinement, including diagnostics and therapeutics
8. Strengthen research and ongoing data collection on VWD pathophysiology, demographic and other patient characteristics, epidemiology, and short- and long-term health outcomes of VWD patients
9. Improve research on the patient outcomes of prophylaxis in selected VWD types of sub-types
10. Toward pursuing the above, re-examine and strengthen patient and community advocacy for VWD through organizational focus, augmented priorities, collaboration and other means as appropriate