Targeting von Willebrand disease: the current status and future directions of management therapies

ABSTRACT

Introduction

von Willebrand disease (VWD) is the commonest inherited bleeding disorder, and is typically caused by deficits in the quantity or quality of von Willebrand factor (VWF).

Areas covered

This review describes the main clinical, diagnostic, and therapeutic aspects of VWD, with particular attention to its management. In addition, standard and avant-garde replacement therapies based on the use of VWF are discussed.

Expert opinion

The goal of treatment for VWD is to reverse the double hemostatic defect resulting from the abnormal or reduced expression of VWF and the concomitant factor VIII (FVIII) deficiency. Treatment consists of managing any bleeds and both short-term prophylaxis (i.e. for surgery or invasive procedures) and long-term prophylaxis. While desmopressin is suitable for most patients with type 1 VWD, VWF/FVIII concentrates are the treatment of choice for the other types of VWD. Beside plasma-derived VWF/FVIII concentrates, whose safety and efficacy have been demonstrated by several clinical trials, products containing only VWF, obtained by plasma fractionation and recombinant DNA technology, have become available and marketed more recently. The clinical use of these VWF-only products is particularly attractive in the setting of surgery and long-term prophylaxis, such as the prevention of recurrent gastrointestinal bleeding in cases of angiodysplasia.

KEYWORDS:

• von Willebrand disease
• management
• therapy
• plasma-derived VWF concentrates
• recombinant VWF

Article highlights

• Von Willebrand disease (VWD) is caused by either a quantitative deficiency or abnormal activity of von Willebrand factor (VWF) and is the most frequent inherited bleeding disorder.

• The aim of treatment is to correct the hemostatic defect caused by the abnormal or deficient VWF and the concomitant reduction of FVIII levels.

• Both plasma-derived and recombinant VWF concentrates are available for replacement therapy of VWD forms unresponsive to DDAVP.

• A recombinant VWF product (vonicog alfa) is a useful treatment for hemostatic coverage in patients undergoing surgery or requiring long-term prophylaxis.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.