Related Experiment Video
Updated: Aug 8, 2026
08:30
Investigating von Willebrand Factor Pathophysiology Using a Flow Chamber Model of von Willebrand Factor-platelet String Formation
Published on: August 14, 2017
Insights into von Willebrand factor proteolysis: clinical implications
1The Arthur Bloom Centre, Department of Haematology, School of Medicine, Cardiff University, Heath Park, Cardiff, South Wales, UK. bowendj@cf.ac.uk
British Journal of Haematology
|May 10, 2006
Summary
Proteolysis of von Willebrand factor (VWF) by ADAMTS13 is crucial. Compromised VWF proteolysis by ADAMTS13 may cause thrombotic thrombocytopenic purpura (TTP) and influence bleeding risk in type 1 von Willebrand disease (VWD).
Area of Science:
- Biochemistry
- Hematology
- Molecular Biology
Background:
- Proteolysis of von Willebrand factor (VWF) by ADAMTS13 is a normal VWF processing step.
- Factors influencing VWF proteolysis can favor increased proteolysis (predisposing to bleeding) or compromise it (linked to thrombotic thrombocytopenic purpura).
Purpose of the Study:
- To review current knowledge of VWF proteolysis by ADAMTS13.
- To propose a novel model for ADAMTS13's role in type 1 von Willebrand disease (VWD) based on vessel wall events during hemostasis.
Main Methods:
- Literature review of VWF proteolysis by ADAMTS13.
- Development of a conceptual model linking VWF proteolysis to type 1 VWD pathophysiology.
Main Results:
- Emerging data suggest factors influencing VWF proteolysis have significant implications for bleeding risk and thrombotic disorders.
- A novel model is proposed suggesting impaired VWF proteolysis at the vessel wall contributes to type 1 VWD.
Conclusions:
- Understanding VWF proteolysis by ADAMTS13 is key to understanding bleeding disorders.
- The proposed model offers new insights into the pathogenesis of type 1 VWD, reframing it within a risk-based concept similar to venous thrombosis.
Related Concept Videos
01:22Formation of the Platelet Plug
The platelet phase, the second stage of hemostasis, commences around 15-20 seconds after an injury. It follows and overlaps with the vascular phase, during which blood vessels constrict to minimize blood loss.
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
01:16Clot Retraction and Fibrinolysis
After a fibrin clot is formed, the next step is clot retraction, a vital process facilitated by platelet contractile proteins, such as actin and myosin. These proteins pull the fibrin strands closer together and condense the clot. This action reduces the size of the clot, creating a smaller, denser structure that effectively seals off the damaged vessel. Clot retraction consolidates the clot and helps with wound healing by bringing the edges of the damaged blood vessel closer together.
01:17Intracellular Signaling Affects Focal Adhesions
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
01:24Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...