Faculty Collaboration Database

Platelet-derived extracellular vesicles released after trauma promote hemostasis and contribute to DVT in mice. J Thromb Haemost 2019 Oct;17(10):1733-1745

Date

07/12/2019

Pubmed ID

31294514

Pubmed Central ID

PMC6773503

DOI

10.1111/jth.14563

Scopus ID

2-s2.0-85072746695 (requires institutional sign-in at Scopus site)   45 Citations

Abstract

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 PEVs 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. PEVs 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 PEVs into circulation compared with healthy controls. These PEVs result in abundant thrombin generation, increased platelet aggregation, decreased bleeding times, and decreased hemorrhage in uncontrolled bleeding. Conversely, PEVs 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 PEVs which are both pro-hemostatic and pro-thrombotic. The effects of PEVs can be mitigated by treatment with HCQ, suggesting the potential use as a form of deep vein thrombosis prophylaxis.

Author List

Dyer MR, Alexander W, Hassoune A, Chen Q, Brzoska T, Alvikas J, Liu Y, Haldeman S, Plautz W, Loughran P, Li H, Boone B, Sadovsky Y, Sundd P, Zuckerbraun BS, Neal MD

Author

Mitchell R. Dyer MD Assistant Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Animals
Blood Platelets
Disease Models, Animal
Extracellular Vesicles
Female
Fibrinolytic Agents
Hemostasis
Humans
Hydroxychloroquine
Male
Mice, Inbred C57BL
Middle Aged
Multiple Trauma
Platelet Aggregation
Platelet Aggregation Inhibitors
Signal Transduction
Thrombin
Time Factors
Venous Thrombosis