Clearance of von Willebrand factor

Abstract

Summary Quantitative deficiencies in von Willebrand factor (VWF) are associated with abnormal hemostasis that can manifest in bleeding or thrombotic complications. Consequently, many studies have endeavored to elucidate the mechanisms underlying the regulation of VWF plasma levels. This review focuses on the role of VWF clearance pathways. A summary of recent developments are provided, including results from genetic studies, the relationship between glycosylation and VWF clearance, the contribution of increased VWF clearance to the pathogenesis of von Willebrand disease and the identification of VWF clearance receptors. These different studies converge in their conclusion that VWF clearance is a complex phenomenon that involves multiple mechanisms. Deciphering how such different mechanisms coordinate their role in this process is but one of the remaining challenges. Nevertheless, a better insight into the complex clearance pathways of VWF may help us to better understand the clinical implications of aberrant clearance in the pathogenesis of von Willebrand disease and perhaps other disorders as well as aid in developing alternative therapeutic approaches.

Active von Willebrand factor predicts 28-day mortality in patients with systemic inflammatory response syndrome

“…22 However, a significant decrease of TSP in nonsurvivors was observed on day 3 only. Taken together, these results support the suggestion that clearance, 17 rather than regulation of activity, is the primary mechanism responsible for controlling aVWF levels.…”

“…15 It is suggested that VWF is released from ECs in an active conformation 10 but thereafter is rapidly cleared by low density lipoprotein receptor-related protein 1. 16,17 Although ADAMTS-13 was not shown to be involved in the process of clearance, 18 there is evidence that proteolysis of multimeric VWF by ADAMTS-13 also leads to the inaccessibility of the A1 domain. 10 In this study, a strong relation between aVWF and ADAMTS-13 was not observed.…”

N-linked glycans within the A2 domain of von Willebrand factor modulate macrophage-mediated clearance

“…2,14 However, accumulating data have demonstrated that macrophages play important roles in regulating VWF clearance in vivo, [21][22][23][24][25][26] and a number of putative macrophage receptors for VWF have been identified. 23,26,38 Critically, however, the specific regions of the VWF glycoprotein involved in modulating interactions with these different macrophage receptors have not been determined.…”

“…15,27,28 Intriguingly, the majority of VWF amino acid substitutions associated with enhanced clearance are clustered within the A1 domain. 14 Emerging evidence suggests that at least some of these VWF mutations result in enhanced macrophage-mediated clearance in vivo. For example, Wohner et al recently showed that specific type 2B VWD variants (R1306Q and V1316M within the A1 domain) result in increased VWF clearance that is predominantly modulated through the macrophage LRP1 receptor.…”

Effect of Hydroxyethyl Starch 200/0.5 on Von Willebrand Factor Serum Level and Activated Partial Thromboplastin Time (Aptt)

“…In this study, sampling point after HES 200 administration was 60 minutes. Therefore, the decline of HES 200 in this study was not influenced by vWF factor half-life in blood circulation (Casari et al 2013, Lenting et al 2014.…”