Von Willebrand Disease Epidemiology, Burden of Illness and Management: A Systematic Review

Abstract

Introduction

Although hereditary von Willebrand disease (VWD) is the most common bleeding disorder, its epidemiology is not well understood. A systematic review (PROSPERO CRD42020197674/CRD42021244374) on the epidemiology/burden of illness of VWD was conducted to better understand patients’ unmet needs.

Methods

Observational studies (published January 1, 2010 to April 14, 2021) were identified in MEDLINE and Embase databases, using free-text keywords and thesaurus terms for VWD and outcomes of interest. Pragmatic web-based searches of the gray literature, including conference abstracts, were performed, and reference lists of retained publications were manually searched for additional sources. Case reports and clinical trials (phase 1–3) were excluded. Outcomes of interest were incidence, prevalence, mortality, patient characteristics, burden of illness, and therapeutic management/treatments currently used for VWD.

Results

Of the 3095 identified sources, 168 were included in this systematic review. Reported VWD prevalence (22 sources) ranged from 108.9 to 2200 per 100,000 in population-based studies and from 0.3 to 16.5 per 100,000 in referral-based studies. Reported times between first symptom onset and diagnosis (two sources; mean 669 days; median 3 years) highlighted gaps in timely VWD diagnosis. Bleeding events reported in 72–94% of the patients with VWD (all types; 27 sources) were mostly mucocutaneous including epistaxis, menorrhagia, and oral/gum bleeding. Poorer health-related quality of life (three sources) and greater health care resource utilization (three sources) were reported for patients with VWD than in general populations.

Conclusion

Available data suggest that patients with VWD experience high disease burden in terms of bleeding, poor quality of life, and health care resource utilization.

Keywords:

• disease burden
• epidemiology
• health-related quality of life
• health care resource utilization
• systematic review
• von Willebrand disease

Data Sharing Statement

The datasets, including the template data extraction form and data extracted from the included studies, are available upon request from corresponding author, Ping Du.

Acknowledgments

The authors thank Teigna Arredondo-Bisono who provided support in the protocol development, data extraction, and analysis. Under the direction of the authors, medical writing support was provided by Joanne Vaughan, Excel Medical Affairs (Fairfield, CT, USA), and was funded by Takeda Development Center Americas, Inc., Lexington, MA, USA.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

PD, GÖ, and ST are employees of Takeda Development Center Americas, Inc., and Takeda stockholders. AB and YM are employees of YOLARX Consultants and received fees from Shire Human Genetic Therapies, Inc., a Takeda company, for conducting this analysis. FTB is an employee of Takeda Pharmaceuticals International AG, and a Takeda stockholder. The authors report no other conflicts of interest in this work.

Additional information

Funding

This work was supported by Shire Human Genetic Therapies, Inc, a Takeda company, Lexington, MA. The sponsor was involved with the protocol development, analysis of identified sources and interpretation of findings, report development, and in the decision to submit the article for publication.