Abstract
Von Willebrand disease (VWD) may be caused by an impaired von Willebrand factor (VWF) synthesis, its increased clearance or abnormal function, or combinations of these factors. It may be difficult to recognize the different contributions of these anomalies. Here we demonstrate that VWD diagnostics gains from measuring platelet VWF, which can reveal a defective VWF synthesis. Measuring platelet VWF revealed that: severe type 1 VWD always coincided with significantly lower platelet and plasma VWF levels, whereas mild forms revealed low plasma VWF levels associated with low or normal platelet VWF levels, and the latter were associated with a slightly shorter VWF survival; type Vicenza (the archetype VWD caused by a reduced VWF survival) featured normal platelet VWF levels despite significantly reduced plasma VWF levels; type 2B patients could have either normal platelet VWF levels associated with abnormal multimer patterns, or reduced platelet VWF levels associated with normal multimer patterns; type 2A patients could have reduced or normal platelet VWF levels, the former associated mainly with type 2A-I, the latter with type 2A-II; plasma and platelet VWF levels were normal in type 2N, except when the defect was associated with a quantitative VWF mutation. Our findings show that measuring platelet VWF helps to characterize VWD, especially the ambiguous phenotypes, shedding light on the mechanisms underlying the disorder.
Highlights
Von Willebrand factor (VWF) is a high-molecular-weight multimeric glycoprotein with a fundamental role in the early stages of hemostasis, promoting the binding of platelet VWF at the site of vascular injury [1]
Type 1 Von Willebrand disease (VWD) was diagnosed on the strength of a homogeneous decrease in plasma VWF:Ag and function (VWF:RCo, VWF:CB and VWF:FVIIIB) in the absence of any evident VWF multimer structural abnormalities
This study shows that measuring platelet VWF can be helpful in characterizing VWD by revealing when VWF synthesis is impaired
Summary
Von Willebrand factor (VWF) is a high-molecular-weight multimeric glycoprotein with a fundamental role in the early stages of hemostasis, promoting the binding of platelet VWF at the site of vascular injury [1]. It serves as a carrier of FVIII [2]. Platelet VWF synthesized by megakaryocytes accounts for 10% to 20% of all the VWF in the blood. It is secreted from the alpha granules at the site of vascular injury
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