Active von Willebrand Factor in patients with a bleeding diathesis

Lisa N Van Der Vorm,Dana Huskens,Lisa Florin,Pieter De Kesel,Mark Roest,Bas De Laat,Katrien M.J Devreese

doi:10.1016/j.tru.2020.100001

Abstract

IntroductionIncreased levels of circulating von Willebrand Factor (VWF) in its active, platelet-binding conformation have been implicated in the pathogenesis of several thrombotic conditions as well as bleeding conditions characterized by severe thrombocytopenia. However, it is unclear whether the proportion of activated VWF in the circulation also plays a role in patients with mild to moderate bleeding without thrombocytopenia. MethodsCitrated plasma samples were collected from 145 patients with a bleeding diathesis with unknown cause. Active VWF levels were measured with an in-house developed ELISA assay. In addition, VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo) and (flow-cytometric) platelet-VWF binding (Plt:VWF) were determined. ResultsActive VWF levels were on average mildly, but not significantly, lowered in patients with a bleeding diathesis compared to the reference interval (especially in individuals with non-O blood groups). Active VWF was not significantly different for subjects with (median 107.4%, IQR 18.3) versus without (median 111.1%, IQR 32.3%) an increased bleeding score, nor between subjects with suspected VWD (median 104%, IQR 20.6%) versus other suspected causes of bleeding diathesis (median 111.7%, IQR 33.3%). ConclusionIn this clinically heterogeneous population of patients with a mild bleeding phenotype, quantification of active VWF levels does not have added diagnostic value to VWF:Ag and VWF activity assays in the diagnosis of unexplained bleeding disorders.

Highlights

Increased levels of circulating von Willebrand Factor (VWF) in its active, platelet-binding conformation have been implicated in the pathogenesis of several thrombotic conditions as well as bleeding conditions characterized by severe thrombocytopenia
HELLP syndrome, associated with on average 2 to 12-fold and 3-fold increased active VWF levels compared to healthy controls, respectively) or the bleeding (e.g. von Willebrand disease (VWD) type 2B) side [5]
In von Willebrand Disease (VWD) type 2B, enhanced binding of platelets to active VWF (2–15 fold increased levels compared to healthy controls [5], due to gain-of-function mutations in the A1 domain) results in clearance of high-molecular-weight (HMW) VWF multimers and platelets, and a bleeding phenotype

Summary

Introduction

Increased levels of circulating von Willebrand Factor (VWF) in its active, platelet-binding conformation have been implicated in the pathogenesis of several thrombotic conditions as well as bleeding conditions characterized by severe thrombocytopenia. HELLP syndrome, associated with on average 2 to 12-fold and 3-fold increased active VWF levels compared to healthy controls, respectively) or the bleeding (e.g. von Willebrand disease (VWD) type 2B) side [5]. In VWD type 2B, enhanced binding of platelets to active VWF (2–15 fold increased levels compared to healthy controls [5], due to gain-of-function mutations in the A1 domain) results in clearance of high-molecular-weight (HMW) VWF multimers and platelets, and a bleeding phenotype.

Results

Conclusion