Language
English
Publication Date
7-1-2024
Journal
Blood Coagulation & Fibrinolysis
DOI
10.1097/MBC.0000000000001309
PMID
38973517
PMCID
PMC11232922
PubMedCentral® Posted Date
7-1-2025
PubMedCentral® Full Text Version
Author MSS
Abstract
Normally, von Willebrand factor (VWF) remains inactive unless its A1A2 domains undergo a shear stress-triggered conformational change. We demonstrated the capacity of a recombinant A2 domain of VWF to bind and to affect fibrin formation, altering the fibrin clot structure. The data indicated that VWF contains an additional binding site for fibrin in the A2 domain that plays a role in the incorporation of VWF to the polymerizing fibrin. This study is to examine the hypothesis that active plasma VWF directly influence fibrin polymerization and the structure of fibrin clots. The study used healthy and type 3 von Willebrand disease (VWD) plasma, purified plasma VWF, fibrin polymerization assays, confocal microscopy and scanning electron microscopy. The exposed A2 domain in active VWF harbors additional binding sites for fibrinogen, and significantly potentiates fibrin formation (P < 0.02). Antibody against the A2 domain of VWF significantly decreased the initial rate of change of fibrin formation (P < 0.002). Clot analyses revealed a significant difference in porosity between normal and type 3 VWD plasma (P < 0.008), further supported by scanning electron microscopy, which demonstrated thicker fibrin fibers in the presence of plasma VWF (P < 0.0003). Confocal immunofluorescence microscopy showed punctate VWF staining along fibrin fibrils, providing visual evidence of the integration of plasma VWF into the fibrin matrix. The study with type 3 VWD plasma supports the hypothesis that plasma VWF directly influences fibrin polymerization and clot structure. In addition, a conformational change in the A1A2 domains exposes a hidden fibrin(ogen) binding site, indicating that plasma VWF determines the fibrin clot structure.
Keywords
von Willebrand Factor, Humans, Fibrin, von Willebrand Disease, Type 3, Binding Sites, Microscopy, Electron, Scanning
Published Open-Access
yes
Recommended Citation
Martinez-Vargas, Marina; Courson, Justin; Gardea, Luis; et al., "The Impact of Von Willebrand Factor on Fibrin Formation and Structure Unveiled With Type 3 Von Willebrand Disease Plasma" (2024). Faculty and Staff Publications. 4036.
https://digitalcommons.library.tmc.edu/baylor_docs/4036