• Yingang Wu, Wei Liu, Yuan Zhou, Tristan Hilton, Zilong Zhao, Min Wang, Jason Yeon, Katie Houck, Perumal Thiagarajan, Fangyi Zhang, Fu-Dong Shi, Xiaoping Wu, Min Li, Jing-Fei Dong, and Jianning Zhang.
• Department of Neurosurgery, Tianjin Institute of Neurology, Tianjin, China.
• Blood. 2018 Sep 6; 132 (10): 1075-1084.

Abstractvon Willebrand factor (VWF) is an adhesive ligand, and its activity is proteolytically regulated by the metalloprotease ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat 13). An elevated level of plasma VWF has been widely considered a marker for endothelial cell activation in trauma and inflammation, but its causal role in these pathological conditions remains poorly defined. Using a fluid percussion injury mouse model, we demonstrated that VWF released during acute traumatic brain injury (TBI) was activated and became microvesicle-bound. The VWF-bound microvesicles promoted vascular leakage and systemic coagulation. Recombinant ADAMTS-13 given either before or after TBI reduced the VWF reactivity with minimal influence on VWF secretion. rADAMTS-13 protected the integrity of endothelial cell barriers and prevented TBI-induced coagulopathy by enhancing VWF cleavage without impairing basal hemostasis. Promoting microvesicle clearance by lactadherin had efficacy similar to that of rADAMTS-13. This study uncovers a novel synergistic action between VWF and cellular microvesicles in TBI-induced vascular leakage and coagulopathy and demonstrates protective effects of rADAMTS-13.© 2018 by The American Society of Hematology.

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