{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T13:01:30Z","timestamp":1783947690854,"version":"3.55.0"},"reference-count":106,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical School of the National and Kapodistrian University of Athens (NKUA)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Antiphospholipid syndrome (APS) is the most common acquired form of thrombophilia and is associated with the presence of antiphospholipid antibodies (aPL) in the patient\u2019s serum. Until now, the \u201cdouble-hit\u201d hypothesis remains the prevailing theory for APS pathogenesis. According to this model, the presence of aPL (first hit) is insufficient to trigger thrombosis. A secondary event, such as an inflammatory trigger or vascular injury (second hit), is required to initiate immunothrombosis, which ultimately leads to thromboembolism. Although immunothrombosis has a critical role in several mechanisms, such as in defense against pathogens, chronic immune system activation by aPL appears to disrupt its protective function. In the last three decades, the role of the complement system has gained increasing recognition in the pathophysiology of APS. aPL are involved in the dysregulation of multiple components, such as platelets, \u03b22-glycoprotein I, and complement factor H, resulting in excessive activation of the complement system. Thus, the complement system is a key driver of thrombosis in APS and stands as a promising target for the development of future therapeutic strategies. In the current review article, we aim to summarize the ongoing research regarding the role of complement system dysregulation in APS-associated thrombosis development, while recognizing potential therapeutic targets. In the era of precision medicine, more data concerning targeted therapeutics in the field of APS are essential.<\/jats:p>","DOI":"10.3390\/jcm14186672","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T12:08:03Z","timestamp":1758542883000},"page":"6672","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Activated Complement System\u2019s Impact in Antiphospholipid Syndrome Thrombosis: From Pathophysiology to Treatment"],"prefix":"10.3390","volume":"14","author":[{"given":"Sofia","family":"Tagara","sequence":"first","affiliation":[{"name":"Laboratory of Hematology, General Hospital of Chania \u201cSt. George\u201d, 73100 Chania, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1034-6510","authenticated-orcid":false,"given":"Serena","family":"Valsami","sequence":"additional","affiliation":[{"name":"Hematology Laboratory and \u0392lood Bank, Aretaieion Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8883-8208","authenticated-orcid":false,"given":"Eleni","family":"Gavriilaki","sequence":"additional","affiliation":[{"name":"Second Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Kyriakou","sequence":"additional","affiliation":[{"name":"Laboratory of Hematology and Blood Bank Unit, \u201cAttikon\u201d University General Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisavet","family":"Grouzi","sequence":"additional","affiliation":[{"name":"Department of Transfusion Service and Clinical Hemostasis, \u201cSaint Savvas\u201d Oncology Hospital, 11522 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1783-5111","authenticated-orcid":false,"given":"Paschalis","family":"Evangelidis","sequence":"additional","affiliation":[{"name":"Second Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paraskevi","family":"Karvouni","sequence":"additional","affiliation":[{"name":"School of Medicine, Aristotle University of Thessaloniki, 54634 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Kaiafa","sequence":"additional","affiliation":[{"name":"1st Propaedeutic Clinic of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, 54634 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9870-8521","authenticated-orcid":false,"given":"Ioannis","family":"Papadakis","sequence":"additional","affiliation":[{"name":"Laboratory of Hematology, General Hospital of Chania \u201cSt. George\u201d, 73100 Chania, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aristarchos","family":"Poulis","sequence":"additional","affiliation":[{"name":"Laboratory of Hematology and Blood Bank Unit, \u201cAttikon\u201d University General Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Petrou","sequence":"additional","affiliation":[{"name":"Laboratory of Hematology and Blood Bank Unit, \u201cAttikon\u201d University General Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Politou","sequence":"additional","affiliation":[{"name":"Hematology Laboratory and \u0392lood Bank, Aretaieion Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Styliani","family":"Kokoris","sequence":"additional","affiliation":[{"name":"Laboratory of Hematology and Blood Bank Unit, \u201cAttikon\u201d University General Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1136\/bmj.287.6399.1088","article-title":"Thrombosis, Abortion, Cerebral Disease, and the Lupus Anticoagulant","volume":"287","author":"Hughes","year":"1983","journal-title":"Br. 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