Platelet VWF provides novel insights into the biology underlying quantitative Von Willebrand Disease

IntroductionPlatelet von Willebrand Factor accounts for 10-20% of total vWF:Ag present in normal platelet-rich plasma. Previous studies of plt-VWF in von Willebrand Disease involved only small numbers of patients. Given... [ view full abstract ]

Introduction

Platelet von Willebrand Factor accounts for 10-20% of total vWF:Ag present in normal platelet-rich plasma. Previous studies of plt-VWF in von Willebrand Disease involved only small numbers of patients. Given the high level of VWF-stored within platelet α-granules, previous in-vitro and in-vivo studies reported that plt-vWF plays a critical role in haemostasis. Given the significant bleeding phenotype observed in patients with Low-vWF, we hypothesized that plt-vWF levels may also be reduced in this cohort. In the largest study of plt-vWF levels performed to date, we systematically examined both plt-vWF antigen and activity levels in patients enrolled in Low-Von WIllebrand in Ireland Cohort study compared to healthy-controls.

Methods

Plt-VWF-antigen and collagen-binding activity levels were determined for 54-patients with Low-vWF levels, compared to 22 normal controls. VWF-antigen and VWF-collagen binding assays were performed using standard ELISA. Bleeding phenotype was evaluated using a physician-directed bleeding assessment tool from which the ISTH BAT score was derived.

Results

Plt-VWF:Ag and plt-VWF:CB levels were both significantly reduced in LoVIC patients compared to healthy controls (mean plt-VWF:Ag 0.16 IU/10⁹/L versus 0.21 IU/10⁹/L, p<0.05; mean plt-VWF:CB 0.18 IU/10⁹/L versus 0.34 IU/10⁹/L, p<0.0001). This supports the hypothesis that reduced-vWF synthesis plays a key role in the pathogenesis underlying Low-vWF levels in this cohort. Although previous studies suggested that platelet vWF levels may influence bleeding risk in patients with type 1 VWD (such that bleeding is attenuated in ‘platelet-normal’ patients), we observed no significant increase in bleeding for Low-vWF patients with reduced compared to normal plt-VWF:Ag.

Conclusions

Our findings demonstrated patients with Low-plasma vWF-levels, plt-VWF levels are also significantly reduced. This finding suggests reduced vWF-synthesis contributes to the pathophysiology of Low-vWF with a defect common to both endothelial cell and megakaryocytic vWF-synthetic compartments. However, quantitative and/or qualitative defects in plt-VWF did not alter the ISTH-BAT scores in LoVIC patients.