New developments in von Willebrand disease

Abstract

Summary 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.

Toward Personalized Treatment for Patients with Low von Willebrand Factor and Quantitative von Willebrand Disease

“…18 In contrast, although it accounts for the majority of VWD cases, the pathobiology underpinning partial quantitative deficiency of VWF, has remained elusive. 13 However, important insights have been gained from several recent cohort studies. 17,[19][20][21][22] These studies have demonstrated that reduced plasma VWF:antigen (VWF:Ag) levels may result from (1) a decrease in VWF biosynthesis within endothelial cells (ECs), (2) a decrease in VWF secretion from EC, or (3) an increase in plasma VWF clearance.…”

“…Accumulating data over recent years has provided important advances in our understanding of VWD pathobiology. 13,[15][16][17] In particular, it has become clear that several distinct subgroups within partial quantitative VWD can now be defined. In this review, these insights into quantitative VWD pathogenesis will be considered.…”

Correcting dominant‐negative von Willebrand disease

“…VWD constitutes the most common inherited bleeding disorder and affects up to 1 in 1000 individuals 2,4 . The majority of VWD is caused by mutations at the VWF gene locus on chromosome 12 5 .…”

“…2,3 VWD constitutes the most common inherited bleeding disorder and affects up to 1 in 1000 individuals. 2,4 The majority of VWD is caused by mutations at the VWF gene locus on chromosome 12. 5 These mutations affect VWF biosynthesis within EC in a variety of different ways, ultimately leading to either quantitative (Type 1 VWD) or qualitative (Types 2A, 2B, 2M, or 2N VWD) VWF deficiencies and a consequent bleeding phenotype.…”

Expresser phenotype determines ABO(H) blood group antigen loading on platelets and von Willebrand factor

“…Interestingly, although H antigen is expressed on platelet-derived VWF, there is no A or B antigen expression 13 , 14 . ABO(H) expression on VWF is important because it has been shown to regulate multiple aspects of VWF biology 15 , 16 . First, ABO affects plasma levels of the VWF-FVIII complex, with significantly lower levels in blood group O compared to non-O subjects 17 .…”