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In selected etiological and stage\u2010specific contexts, systemic thrombocytopenia may coexist with intrahepatic platelet enrichment and activation, making circulating platelet counts insufficient to reflect local fibrotic activity. This review synthesizes current evidence to define platelet dynamics along the circulation\u2013spleen\u2013liver axis and their multicellular crosstalk within the fibrotic microenvironment, aiming to clarify how platelets integrate into a self\u2010reinforcing fibrogenic network and identify potential therapeutic strategies beyond correcting systemic thrombocytopenia. Systemic thrombocytopenia and intrahepatic platelet enrichment are not mutually exclusive; this paradox renders circulating platelet counts a poor surrogate for intrahepatic fibrotic activity. In the liver, platelets integrate thrombotic, inflammatory, angiogenic, and regenerative signals via mediator release (TGF\u2010\u03b21, PDGF\u2010BB, CXCL4) and interactions with hepatocytes, Kupffer cells (KCs), liver sinusoidal endothelial cells (LSECs), and hepatic stellate cells (HSCs). Platelet\u2010hepatocyte crosstalk exerts opposing effects: injury amplification versus regeneration promotion. Platelet\u2010KC interactions are pro\u2010inflammatory and pro\u2010fibrotic, yet include CLEC4F\u2010mediated phagocytosis that limits excessive platelet accumulation. LSEC capillarization creates a pro\u2010thrombotic niche, where platelet adhesion activates NF\u2010\u03baB, provides P\u2010selectin docking for leukocytes, and drives microthrombosis. Platelet\u2010HSC communication is directly pro\u2010fibrotic via coordinated TGF\u2010\u03b21 and PDGF\u2010BB signalling, reinforced by bidirectional loops. Therapeutically, correction of peripheral thrombocytopenia should be distinguished from investigational strategies aimed at modulating pathogenic intrahepatic platelet activity.<\/jats:p>","DOI":"10.1111\/liv.70848","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:30:52Z","timestamp":1787315452000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intrahepatic Platelets Orchestrate Microenvironmental Remodelling and Cellular Crosstalk in Liver Fibrosis"],"prefix":"10.1111","volume":"46","author":[{"given":"Zhi","family":"Chen","sequence":"first","affiliation":[{"name":"Beijing Clinical Research Institute Beijing Friendship Hospital, Capital Medical University  Beijing China"},{"name":"State Key Lab of Digestive Health Beijing Friendship Hospital, Capital Medical University  Beijing China"},{"name":"National Clinical Research Center of Digestive Diseases Beijing Friendship 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