{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:04:34Z","timestamp":1792087474395,"version":"4.4.0"},"reference-count":31,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Siemens Healthcare"},{"name":"ThermoFisher Scientific"},{"name":"Wefern"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Severe COVID-19 is often associated with coagulopathy and thrombotic complications. The underlying mechanisms are complex and multifactorial, involving platelet activation, dysregulation of the complement cascade, fibrinolytic imbalance, release of pro-inflammatory cytokines, immunothrombosis, antiphospholipid antibodies, and alterations in the von Willebrand factor (vWF)\/ADAMTS13 axis. These pathways are also implicated in thrombotic microangiopathies (TMAs), characterized by endothelial injury and widespread microvascular thrombosis. In this prospective monocentric observational study, we investigated whether COVID-19-associated coagulopathy meets the criteria for TMA and evaluated the roles of complement activation and vWF\/ADAMTS13 imbalance in disease severity. Forty-three hospitalized COVID-19 patients were enrolled and stratified by disease severity. Blood samples collected at admission were analyzed for hematologic, coagulation, inflammatory, and complement parameters. A 30-day follow-up recorded survival and thrombotic events. All patients showed elevated vWF and factor VIII levels; however, only vWF collagen-binding activity (vWF-CBA) significantly correlated with disease severity. ADAMTS13 activity remained above 60% in all cases, and no schistocytes were detected, arguing against a diagnosis of classical TMA. Nevertheless, the vWF-CBA\/ADAMTS13 ratio was significantly higher in severe cases, particularly in unvaccinated individuals, suggesting endothelial dysregulation. Complement analysis revealed increased C5a levels and decreased C3b\/iC3b ratios in severe disease, consistent with complement activation and consumption. C2 levels were also lower in these patients. Although complement activation and vWF\/ADAMTS13 imbalance did not directly correlate, both pathways showed a similar trend according to disease severity. Overall, our findings indicate that COVID-19-related coagulopathy does not fulfill the criteria for classical TMA but shows features of complement-mediated endothelial injury and vWF dysregulation. The vWF-CBA may serve as a rapid, standardized tool for assessing endothelial dysfunction. Activation of the complement system, particularly via the lectin and alternative pathways, appears central to the prothrombotic state in severe COVID-19.<\/jats:p>","DOI":"10.3390\/ijms26115395","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T10:10:16Z","timestamp":1749031816000},"page":"5395","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Is COVID-19 Coagulopathy a Thrombotic Microangiopathy? A Prospective, Observational Study"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2601-1579","authenticated-orcid":false,"given":"Mauro","family":"Silingardi","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Ospedale Maggiore \u201cCarlo Alberto Pizzardi\u201d, 40133 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6041-2195","authenticated-orcid":false,"given":"Fulvia","family":"Zappulo","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ada","family":"Dormi","sequence":"additional","affiliation":[{"name":"Biostatistics, Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum-University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attilia Maria","family":"Pizzini","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ospedale Maggiore \u201cCarlo Alberto Pizzardi\u201d, 40133 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4864-3809","authenticated-orcid":false,"given":"Chiara","family":"Donadei","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum-University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Cappuccilli","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum-University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Fantoni","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ospedale Maggiore \u201cCarlo Alberto Pizzardi\u201d, 40133 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Zaccaroni","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ospedale Maggiore \u201cCarlo Alberto Pizzardi\u201d, 40133 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5591-7663","authenticated-orcid":false,"given":"Valeria","family":"Pizzuti","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Cilloni","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia, Intensive Care and EMS, Ospedale Maggiore \u201cCarlo Alberto Pizzardi\u201d, 40133 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Tantillo","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia, Intensive Care and EMS, Ospedale Maggiore \u201cCarlo Alberto Pizzardi\u201d, 40133 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Guidi","sequence":"additional","affiliation":[{"name":"Laboratorio Unico Metropolitano, AUSL Bologna, 40133 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Mancini","sequence":"additional","affiliation":[{"name":"Laboratorio Unico Metropolitano, AUSL Bologna, 40133 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5473-8551","authenticated-orcid":false,"given":"Gaetano","family":"La Manna","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum-University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4160-8840","authenticated-orcid":false,"given":"Giorgia","family":"Comai","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Kidney Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy"},{"name":"Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum-University of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s10238-021-00769-x","article-title":"High levels of Von Willebrand factor markers in COVID-19: A systematic review and meta-analysis","volume":"22","author":"Rostami","year":"2022","journal-title":"Clin. 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