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Review
. 2020 Nov;191(3):329-339.
doi: 10.1111/bjh.16681. Epub 2020 May 12.

New developments in von Willebrand disease

Helen Fogarty  1   2 , Dearbhla Doherty  1 , James S O'Donnell  1   2   3
Affiliations
Review

New developments in von Willebrand disease

Helen Fogarty et al. Br J Haematol. 2020 Nov.

Abstract

Von Willebrand disease (VWD) constitutes the most common inherited human bleeding disorder. It is associated with a mucocutaneous bleeding phenotype that can significantly impact upon quality of life. Despite its prevalence and associated morbidity, the diagnosis and subclassification of VWD continue to pose significant clinical challenges. This is in part attributable to the fact that plasma von Willebrand factor (VWF) levels vary over a wide range in the normal population, together with the multiple different physiological functions played by VWF in vivo. Over recent years, substantial progress has been achieved in elucidating the biological roles of VWF. Significant advances have also been made into defining the pathophysiological mechanisms underpinning both quantitative and qualitative VWD. In particular, several new laboratory assays have been developed that enable more precise assessment of specific aspects of VWF activity. In the present review, we discuss these recent developments in the field of VWD diagnosis, and consider how these advances can impact upon clinical diagnostic algorithms for use in routine clinical practice. In addition, we review some important recent advances pertaining to the various treatment options available for managing patients with VWD.

Keywords: Low VWF; von Willebrand disease; von Willebrand factor.

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Figures

Figure 1:
Figure 1:. Biology underlying novel VWF-Gp1b functional activity assays.
(i) In the traditional VWF:RCo assay, VWF binding to Gp1b is induced by the addition of ristocetin to trigger platelet agglutination and increased optical density; (ii) In the VWF:Gp1bR assay, recombinant Gp1b is expressed on latex particles rather than platelets. VWF binding is again induced by addition of ristocetin. (iii) In the VWF:Gp1bM assay, the recombinant Gp1b molecule contains a number of again of function mutations that enable VWF interaction without the need for addition of ristocetin. Adapted from (Vangenechten, et al 2018)
Figure 2:
Figure 2:. VWF ligand interaction sites including different collagen binding sites.
Figure 3:
Figure 3:. Suggested VWD diagnostic algorithm with defined threshold cut-offs
Adapted from UKHCDO guidelines (Laffan, et al 2014)
See this image and copyright information in PMC

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