Gastrointestinal bleeding in von Willebrand patients: special diagnostic and management considerations

ABSTRACT

Introduction

Severe and recurrent gastrointestinal (GI) bleeding caused by angiodysplasia is a significant problem in patients with von Willebrand disease (VWD) and in those with acquired von Willebrand syndrome (AVWS). At present, angiodysplasia-related GI bleeding is often refractory to standard treatment including replacement therapy with von Willebrand factor (VWF) concentrates and continues to remain a major challenge and cause of significant morbidity in patients despite advances in diagnostics and therapeutics.

Areas Covered

This paper reviews the available literature on GI bleeding in VWD patients, examines the molecular mechanisms implicated in angiodysplasia-related GI bleeding, and summarizes existing strategies in the management of bleeding GI angiodysplasia in patients with VWF abnormalities. Suggestions are made for further research directions.

Expert Opinion

Bleeding from angiodysplasia poses a significant challenge for individuals with abnormal VWF. Diagnosis remains a challenge and may require multiple radiologic and endoscopic investigations. Additionally, there is a need for enhanced understanding at a molecular level to identify effective therapies. Future studies of VWF replacement therapies using newer formulations as well as other adjunctive treatments to prevent and treat bleeding will hopefully improve care.

Plain Language Summary

Von Willebrand disease (VWD) is the most common inherited bleeding disorder. It is caused by problems with von Willebrand factor (VWF), a protein in blood that helps stop bleeding. People with VWD either have low levels of VWF or VWF that does not work properly. The disease causes bleeding symptoms in 1 in 1000 individuals. Three main types of VWD exist. Depending on the type, people can have minimal symptoms or serious bleeding that needs hospital care.

Patients with severe VWD may often experience repeated bleeding from the gastrointestinal tract. This is usually due to the formation of abnormal fragile vessels (malformations) called angiodysplasia, which have been linked to the absence or abnormal function of VWF. These fragile vessels are very difficult to find and diagnose. At present, available treatments for angiodysplasia, including long-term VWF replacement therapy, are not very effective. As a result, VWD patients with angiodysplasia have a poor quality of life.

More research is needed to better evaluate current treatments and explore the contribution of abnormal VWF in the development of angiogenesis and angiodysplasia in VWD which may reveal new targets for treatment.

KEYWORDS:

• Angiodysplasia
• bleeding disorders
• vascular abnormalities
• von Willebrand disease
• von Willebrand factor
• gastrointestinal bleeding

Article highlights

• Angiodysplasia, the major cause of gastrointestinal bleeding in patients with VWD, is difficult to manage and causes considerable morbidity.

• Current therapeutic approaches have limited efficacy and fail to directly address underlying pathogenic mechanisms.

• The proposed molecular mechanisms implicated in the development of angiodysplasia in VWD as well as current diagnostic strategies and standard treatment options are discussed.

• Prophylactic treatment with VWF-containing concentrates remains the mainstay of treatment for patients with repeated gastrointestinal angiodysplastic bleeding and a multi-disciplinary/specialty approach is required.

• Further research is critical to properly evaluate existing therapies and identify new treatments to improve patient outcomes.

Acknowledgments

The authors thank Julie Grabell, Department of Medicine at Queen’s University, for general administrative support.

Declaration of interest

PD James has received research funding from Takeda, CSL Behring, and Bayer and is a consultant for Band Therapeutics and Star Therapeutics.

M Sholzberg has received unrestricted research funding from Octapharma, CSL Behring, and honoraria for advisory boards from Octapharma.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.