{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:41:30Z","timestamp":1790905290965,"version":"4.1.0"},"reference-count":321,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008993","name":"University of Zagreb","doi-asserted-by":"publisher","award":["10106-22-3071"],"award-info":[{"award-number":["10106-22-3071"]}],"id":[{"id":"10.13039\/100008993","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>This review presents an innovative and timely exploration of how cytoprotection can serve as a cohesive therapeutic approach by which to address the hemorrhage\u2013thrombosis paradox. Presenting counteraction of both hemorrhage and thrombosis as phase-dependent outcomes of vascular dysregulation, the manuscript synthesizes conceptual, experimental, and clinical evidence into a unified systems-level model focused on the stable gastric pentadecapeptide BPC 157, which acts as a cytoprotective mediator. In rodents, BPC 157 can simultaneously counteract hemorrhage and thrombosis without directly affecting the coagulation cascade (aggregometry, thromboelastometry). This cytoprotective framework (decreased hemorrhage, decreased thrombosis) stands with presentation of both hemorrhage and thrombosis in the wound, arrhythmias, and Virchow triad, and resolution of these disturbances. As proof of the concept (full cytoprotective effect), a vasoprotective cytoprotective mediator capable of bidirectional regulation, BPC 157, is effective for wound healing, arrhythmia control, and normalization of Virchow\u2019s triad (i.e., following major injuries, occlusion\/occlusion-like syndromes). As a comparison from a cytoprotective (partial vs. full) standpoint, conventional agents\u2014anticoagulants, antiplatelet drugs, and fibrinolytics\u2014provide only partial protection by targeting isolated components of hemostasis. Beta blockers, calcium channel blockers, prostaglandins, NO modulators, ACE inhibitors, and statins each exert broader cytoprotective effects; however, these actions remain incomplete and context-dependent, typically unidirectional, dose-limited, or are achieved at the expense of opposing pathological risks. Contrarily, for BPC 157, decreased hemorrhage (including both anticoagulants and antiplatelet agents), decreased thrombosis, effective wound healing, arrhythmia control, and normalization of Virchow\u2019s triad involve preservation of endothelial integrity, normalization of microcirculation, modulation of the NO system, stabilization of hemostatic balance, and recruitment of adaptive collateral pathways. Nevertheless, reliance on preclinical models necessitates further clinical validation.<\/jats:p>","DOI":"10.3390\/ph19030463","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T09:23:03Z","timestamp":1773307383000},"page":"463","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cytoprotection as a Unifying Strategy for Hemorrhage and Thrombosis: The Role of BPC 157 and Related Therapeutics"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7952-2252","authenticated-orcid":false,"given":"Predrag","family":"Sikiric","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Barisic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Udovicic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Lovric Bencic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Balenovic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean","family":"Strinic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, 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