Unwinding the von Willebrand factor strings puzzle

Area of Science:

• Hematology
• Cell Biology
• Biochemistry

Background:

• Endothelial cells synthesize and store ultra-large von Willebrand factor (VWF) multimers.
• Upon secretion, VWF is typically cleaved by ADAMTS13, but some UL-VWF can remain anchored to endothelium.
• These anchored multimers form VWF 'strings' that can interact with platelets and other cells.

Purpose of the Study:

• To review the characteristics of VWF strings.
• To discuss the potential role of VWF strings in physiological and pathological conditions.
• To explore the relevance of VWF strings in the absence of ADAMTS13.

Main Methods:

• Literature review of studies on VWF strings.
• Analysis of VWF string formation and function in vitro and in vivo.
• Discussion of findings in the context of ADAMTS13 activity.

Main Results:

• VWF strings have been visualized in vivo and exhibit extraordinary length.
• These strings possess platelet-binding sites and can tether leukocytes and infected red blood cells.
• Most studies on VWF strings have been conducted in the absence of ADAMTS13.

Conclusions:

• The functional role of VWF strings in healthy individuals and various disease states remains largely unknown.
• The properties of VWF strings in the absence of ADAMTS13 warrant further investigation for understanding (patho)physiologic mechanisms.
• Further research is needed to elucidate the significance of VWF strings in normal hemostasis and disease.