{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:50:03Z","timestamp":1760403003872,"version":"build-2065373602"},"reference-count":98,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Platelets play a pivotal role in coagulation, traditionally recognized for their involvement in thrombin generation via the prothrombinase complex and for regulating thrombopoietin (TPO) synthesis through platelet-mediated TPO uptake. However, recent studies suggest that TPO homeostasis involves more dynamic, feedback-driven mechanisms, though these interactions remain incompletely described and experimentally confirmed. The interplay between platelet activating factor (PAF) secretion, fibrinolysis, interleukin-6 (IL-6) signalling, hepatic TPO synthesis, as well as the complexity of platelet subpopulations, emphasises platelets\u2019 multifaceted role in haemostasis and haematopoiesis. Our article investigates novel pathways by which fibrinogen degradation products (FgDPs) influence plasminogen and TPO synthesis, focusing on the interconnection between procoagulant platelets, platelet-derived messengers, and fibrinolytic processes. In this work several intermediary mechanisms are hypothesised, including the FgDP-IL-6-plasminogen pathway, the PAF-IL-6-TPO pathway, and the thrombin-FgDP-IL-6-TPO pathway, which may link FgDP and plasminogen biosynthesis with platelet activation, cytokine release, and thrombopoiesis regulation. The proposed mechanisms involve secretion of PAF by procoagulant platelets, inducing IL-6 synthesis in endothelial cells, fibroblasts, and vascular smooth muscle cells. Subsequently, IL-6 stimulates hepatocyte-driven TPO production, potentially serving as a feedback mechanism to restore platelet counts following coagulation. Furthermore, fibrinolysis-generated FgDPs may further enhance IL-6 release, implying alternative routes for TPO regulation. Our hypotheses challenge the prevailing view that platelet numbers alone dictate TPO homeostasis. Therefore, we propose that inflammatory and fibrinolytic signals actively regulate TPO homeostasis, challenging the platelet-count-centric paradigm. These insights provide a new perspective on haematopoiesis and suggest novel therapeutic targets for thrombocytopenia and coagulation disorders, highlighting the need for further experimental validation.<\/jats:p>","DOI":"10.3390\/life15101593","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:13:27Z","timestamp":1760361207000},"page":"1593","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Interconnected World of Coagulation Factors, Platelets and Plasminogen: A Novel Perspective on Biosynthetic Regulation"],"prefix":"10.3390","volume":"15","author":[{"given":"Ivan","family":"Bergo","sequence":"first","affiliation":[{"name":"Faculty of Medicine in English Campus Hamburg, George Emil Palade University of Medicine, Pharmacy, Science and Technology, 540139 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3767-4861","authenticated-orcid":false,"given":"Mark","family":"Slevin","sequence":"additional","affiliation":[{"name":"Center for Advanced Medical and Pharmaceutical Research (CCAMF), George Emil Palade University of Medicine, Pharmacy, Science and Technology, 540139 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3833-0184","authenticated-orcid":false,"given":"Ylenia","family":"Pastorello","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Embryology, George Emil Palade University of Medicine, Pharmacy, Science and Technology, 540139 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron","family":"H\u00f6hne","sequence":"additional","affiliation":[{"name":"Faculty of Medicine in English Campus Hamburg, George Emil Palade University of Medicine, Pharmacy, Science and Technology, 540139 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9704-869X","authenticated-orcid":false,"given":"Amelia","family":"Tero-Vescan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, George Emil Palade University of Medicine, Pharmacy, Science and Technology, 540139 T\u00e2rgu Mure\u0219, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1172\/JCI109634","article-title":"Humoral Factor That Specifically Regulates Factor X Levels in Rabbits (Coagulopoietin-X)","volume":"64","author":"Trauber","year":"1979","journal-title":"J. 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