Diagnosis and Disease Burden of Von Willebrand Disease in a Large US Population Based-Dataset
Authors: Sholzberg Michelle , Weyand Angela C , Lai Jacob S , Kim Benjamin , Patou Gary , Engel-Nitz Nicole M. , Amos Qiana , Sidonio, Jr. Robert F. 
Published: December 2024

Introduction: Von Willebrand disease (VWD) is the most common inherited bleeding disorder, affecting up to 1% of the population. Patients with VWD experience excessive bleeding, but bleeding types, severity, and frequency vary. Although improved recently, diagnosis continues to be delayed, which interferes with effective management. To further understand the prevalence of VWD diagnosis and disease burden in the United States, we evaluated the largest, single-source, US VWD administrative and laboratory dataset.
Objectives: To describe the real-world prevalence and clinical burden of von Willebrand disease in the US.
Methods: This retrospective study included data from commercial and Medicare Advantage members with claims of VWD during the study period (January 2007 to February 2023) in the Optum Research Database of administrative data; data included linked available laboratory test data. Patients were characterized as having VWD if they had 1) ≥2 claims with an ICD-9 or ICD-10 code for a VWD diagnosis at least 30 days apart (286.4, D68.0x), 2) had ≥1 claim for a VWD-specific treatment (i.e., desmopressin, recombinant VWF, VWF/FVIII concentrates, tranexamic acid), or 3) had ≥1 laboratory result with a von Willebrand factor antigen (VWF:Ag) &lt;50 IU/dL (VWF:Ag was chosen over VWF:RCo to ensure a more accurate diagnosis). Patients were included if they had ≥6 months of health insurance coverage before and after the index date (defined as the earliest date with a VWD-related claim or laboratory record). Data reported herein are from the 6-month period after the index date.
Patient demographics were derived from enrollment information, and clinical characteristics were assessed Types and frequencies of bleeding events were evaluated. VWD-specific lab test results and treatments, including blood transfusions, were described.
Results: 12,077 patients met inclusion criteria for the diagnosis of VWD. Of these, 6,335 had ≥2 claims for VWD diagnosis; 5,568 had ≥1 claim for a VWD treatment; and 174 had ≥1 laboratory value of VWF:Ag &lt;50 IU/dL. Bleeding events and treatments received were similar across defined VWD cohorts. Mean (SD) age of patients with VWD was 44.3 (23.1) years, with 17.6% of patients &lt;18 years old. The majority of patients with VWD were female (66%) and had commercial insurance (73%).
In VWD patients with one or more bleeds, 59% of patients had claims for anemia. Heavy menstrual bleeding was recorded in 44% of female patients with VWD. Common bleeding events for all patients included gastrointestinal bleeds (12%), epistaxis (11%), post-operative hemorrhage (10%), intracranial hemorrhage (8%), post-injury hemorrhage (7%), hematuria (7%), bruising (5%), joint bleeds (1%), and muscle bleeds (1%).
66% of patients with VWD received VWD-associated treatments that were captured in a medical claim. Treatments used included desmopressin (70%), hormonal therapy (28%), tranexamic acid (15%), and VWF-containing concentrate (5%). 23% of patients treated for VWD received blood transfusions.
For VWD patients who had a VWF:Ag laboratory result, the majority had values &lt;50 IU/dL. Among these patients, 55% had VWF:Ag &lt;20 IU/dL.
Discussion: We analyzed a 6-month period after VWD diagnosis over a 14-year timeframe in this analysis. Both heavy menstrual bleeding and epistaxis may be under captured in patient claims data and may precede and lead to a VWD diagnosis. Not all products used to treat VWD were available during the time span of the study, and some products may be initiated &gt;6 months after diagnosis. Interestingly, a high proportion of patients had VWF:Ag laboratory values &lt;20 IU/dL, suggesting the prevalence of severe VWD (Wynn, ISTH 2024) may be higher than previously reported. Additional data cuts and analyses will be presented at the ASH conference.
Conclusions: Including VWD treatment claims and laboratory values has provided an almost doubling of potential VWD patients identified compared with using ICD diagnostic claims alone. Patients exhibited similar bleeding events and treatments across these diagnostic cohorts. In patients with bleeding events, the majority had anemia, with almost a quarter of those treated requiring blood transfusions. There still exists a wide gap in VWD patient care and an ongoing unmet need for better diagnostic vigilance and disease burden understanding to enable appropriate treatments for VWD patients to mitigate bleeding sequelae, especially anemia.