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The hepatic stellate cell (HSC) agonist Concanavalin A (ConA) rapidly induces hepatitis, which progresses to hepatic fibrosis after serial exposure for 8\u2009weeks. Extravascular platelets were intercalated throughout normal liver parenchyma, with ConA treatment activating resident platelets to degranulate and display P\u2010selectin. HSCs matured from activated human induced pluripotent stem cells or the human LX\u20102 cell line released extracellular vesicles (EVs) that stimulated platelet aggregation, yet these particles lacked known platelet agonists, and this response differed from established behaviors. Enzymatic assays, biologic, chemical and aptamer inhibitors, immunohistochemistry, qPCR, REN siRNA, and western blotting elucidate a novel HSC\u2010EV mediated pathway to platelet activation. 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