{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T19:51:41Z","timestamp":1793389901956,"version":"4.5.0"},"reference-count":75,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T00:00:00Z","timestamp":1635206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Serious vaccine-associated side effects are very rare. Major complications of vaccines are thrombocytopenia and thrombosis in which pathogenetic mechanism is consistent with endotheliopathy characterized by \u201cattenuated\u201d sepsis-like syndrome, leading to the activation of inflammatory and microthrombotic pathway. In the COVID-19 pandemic, acute respiratory distress syndrome caused by microthrombosis has been the major clinical phenotype from the viral sepsis in association with endotheliopathy-associated vascular microthrombotic disease (EA-VMTD), sometimes presenting with thrombotic thrombocytopenic purpura (TTP)-like syndrome. Often, venous thromboembolism has coexisted due to additional vascular injury. In contrast, clinical phenotypes of vaccine complication have included \u201csilent\u201d immune thrombocytopenic purpura (ITP-like syndrome), multiorgan inflammatory syndrome, and deep venous thrombosis (DVT), cerebral venous sinus thrombosis (CVST) in particular. These findings are consistent with venous (v) EA-VMTD. In vEA-VMTD promoted by activated complement system following vaccination, \u201cconsumptive\u201d thrombocytopenia develops as ITP-like syndrome due to activated unusually large von Willebrand factor (ULVWF) path of hemostasis via microthrombogenesis. Thus, the pathologic phenotype of ITP-like syndrome is venous microthrombosis. Myocarditis\/pericarditis and other rare cases of inflammatory organ syndrome are promoted by inflammatory cytokines released from activated inflammatory pathway, leading to various organ endotheliitis. Vaccine-associated CVST is a form of venous combined \u201cmicro-macrothrombosis\u201d composed of binary components of \u201cmicrothrombi strings\u201d from vEA-VMTD and \u201cfibrin meshes\u201d from vaccine-unrelated incidental vascular injury perhaps such as unreported head trauma. This mechanism is identified based on \u201ctwo-path unifying theory\u201d of in vivo hemostasis. Venous combined micro-macrothrombosis due to vaccine is much more serious thrombosis than isolated distal DVT made of macrothrombus. This paradigm changing novel concept of combined micro-macrothrombosis implies the need of combined therapy of a complement inhibitor and anticoagulant for CVST and other complex forms of DVT.<\/jats:p>","DOI":"10.3390\/medicina57111163","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T23:54:33Z","timestamp":1635292473000},"page":"1163","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Vaccine-Associated Thrombocytopenia and Thrombosis: Venous Endotheliopathy Leading to Venous Combined Micro-Macrothrombosis"],"prefix":"10.3390","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9401-7684","authenticated-orcid":false,"given":"Jae C.","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Medicine, University of California Irvine School of Medicine, Irvine, CA 92868, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Bradford","family":"Hawley","sequence":"additional","affiliation":[{"name":"Department of Medicine, Wright State University Boonshoft School of Medicine, Dayton, OH 45435, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/ejh.13665","article-title":"COVID-19 vaccine-associated immune thrombosis and thrombocytopenia (VITT): Diagnostic and therapeutic recommendations for a new syndrome","volume":"107","author":"Franchini","year":"2021","journal-title":"Eur. J. Haematol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Diaz, G.A., Parsons, G.T., Gering, S.K., Meier, A.R., Hutchinson, I.V., and Robicsek, A. (2021). Myocarditis and Pericarditis After Vaccination for COVID-19. 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