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Platelet‐derived extracellular vesicles released after trauma promote hemostasis and contribute to DVT in mice
Author(s) -
Dyer Mitchell R.,
Alexander Wyeth,
Hassoune Adnan,
Chen Qiwei,
Brzoska Tomasz,
Alvikas Jurgis,
Liu Yingjie,
Haldeman Shan,
Plautz Will,
Loughran Patricia,
Li Hui,
Boone Brian,
Sadovsky Yoel,
Sundd Prithu,
Zuckerbraun Brian S.,
Neal Matthew D.
Publication year - 2019
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.14563
Subject(s) - thrombus , platelet , hemostasis , thrombosis , medicine , platelet activation , bleeding time , venous thrombosis , deep vein , anesthesia , pharmacology , platelet aggregation
Background Traumatic injury can lead to dysregulation of the normal clotting system, resulting in hemorrhagic and thrombotic complications. Platelet activation is robust following traumatic injury and one process of platelet activation is to release of extracellular vesicles ( PEV ) that carry heterogenous cargo loads and surface ligands. Objectives We sought to investigate and characterize the release and function of PEV s generated following traumatic injury. Methods PEV content and quantity in circulation following trauma in humans and mice was measured using flow cytometry, size exclusion chromatography, and nanoparticle tracking analysis. PEV s were isolated from circulation and the effects on thrombin generation, bleeding time, hemorrhage control, and thrombus formation were determined. Finally, the effect of hydroxychloroquine ( HCQ ) on PEV release and thrombosis were examined. Results Human and murine trauma results in a significant release of PEV s into circulation compared with healthy controls. These PEV s result in abundant thrombin generation, increased platelet aggregation, decreased bleeding times, and decreased hemorrhage in uncontrolled bleeding. Conversely, PEV s contributed to enhanced venous thrombus formation and were recruited to the developing thrombus site. Interestingly, HCQ treatment resulted in decreased platelet aggregation, decreased PEV release, and reduced deep vein thrombosis burden in mice. Conclusions These data demonstrate that trauma results in significant release of PEV s which are both pro‐hemostatic and pro‐thrombotic. The effects of PEV s can be mitigated by treatment with HCQ , suggesting the potential use as a form of deep vein thrombosis prophylaxis.