{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T04:16:29Z","timestamp":1792988189890,"version":"4.5.0"},"reference-count":100,"publisher":"Georg Thieme Verlag KG","issue":"05","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Thromb Hemost"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombotic thrombocytopenia (VITT) are rare, iatrogenic immune-mediated conditions with high rates of thrombosis-related morbidity and mortality. HIT is a long-recognized reaction to the administration of the common parenterally administered anticoagulant heparin (or its derivatives), while VITT is a new, distinct syndrome occurring in response to adenovirus-based vaccines against coronavirus disease 2019 and potentially other types of vaccines. A feature of both HIT and VITT is paradoxical thrombosis despite a characteristic low platelet count, mediated by the presence of platelet-activating antibodies to platelet factor 4. Several additional factors have also been suggested to contribute to clot formation in HIT and\/or VITT, including monocytes, tissue factor, microparticles, endothelium, the formation of neutrophil extracellular traps, complement, procoagulant platelets, and vaccine components. In this review, we discuss the literature to date regarding mechanisms contributing to thrombosis in both HIT and VITT and explore the pathophysiological similarities and differences between the two conditions.<\/jats:p>","DOI":"10.1055\/s-0043-1761269","type":"journal-article","created":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T23:55:09Z","timestamp":1674863709000},"page":"444-452","source":"Crossref","is-referenced-by-count":27,"title":["Mechanisms of Thrombosis in Heparin-Induced Thrombocytopenia and Vaccine-Induced Immune Thrombotic Thrombocytopenia"],"prefix":"10.1055","volume":"49","author":[{"given":"Maria V.","family":"Selvadurai","sequence":"additional","affiliation":[{"name":"The Alfred Hospital, Melbourne, VIC, Australia"},{"name":"ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel J.","family":"Favaloro","sequence":"additional","affiliation":[{"name":"Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Sydney Centres for Thrombosis and Haemostasis, NSW Health Pathology, Westmead Hospital, Westmead, NSW, Australia"},{"name":"School of Dentistry and Medical Sciences, Faculty of Science and Health, Charles Sturt University, Wagga Wagga, NSW, Australia"},{"name":"School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Westmead Hospital, Westmead, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivien M.","family":"Chen","sequence":"additional","affiliation":[{"name":"ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia"},{"name":"Department of Haematology, Concord Repatriation General Hospital and NSW Health Pathology, Sydney, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2023,1,27]]},"reference":[{"issue":"08","key":"ref1","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1055\/s-0042-1749395","article-title":"Heparin: the journey from parenteral agent to nasal delivery","volume":"48","author":"G Carpen\u00e8","year":"2022","journal-title":"Semin Thromb Hemost"},{"issue":"02","key":"ref2","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1001\/archsurg.1958.01280200041005","article-title":"Arterial embolism occurring during systemic heparin therapy","volume":"76","author":"R E Weismann","year":"1958","journal-title":"AMA Arch Surg"},{"key":"ref3","first-page":"430","article-title":"Heparin-induced thrombocytopenia in man","volume":"59","author":"S Gollub","year":"1962","journal-title":"J Lab Clin Med"},{"issue":"06","key":"ref4","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.7326\/0003-4819-71-6-1121","article-title":"Heparin-induced thrombocytopenia. An unexpected response to treatment of consumption coagulopathy","volume":"71","author":"E A Natelson","year":"1969","journal-title":"Ann Intern Med"},{"issue":"03","key":"ref5","first-page":"409","article-title":"Heparin induced thrombocytopenia with thrombotic and hemorrhagic manifestations","volume":"136","author":"G R Rhodes","year":"1973","journal-title":"Surg Gynecol Obstet"},{"issue":"22","key":"ref6","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1056\/NEJMoa2104840","article-title":"Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination","volume":"384","author":"A Greinacher","year":"2021","journal-title":"N Engl J Med"},{"issue":"23","key":"ref7","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1056\/NEJMoa2105385","article-title":"Pathologic antibodies to platelet factor 4 after ChAdOx1 nCoV-19 vaccination","volume":"384","author":"M Scully","year":"2021","journal-title":"N Engl J Med"},{"issue":"22","key":"ref8","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1056\/NEJMoa2104882","article-title":"Thrombosis and thrombocytopenia after ChAdOx1 nCoV-19 vaccination","volume":"384","author":"N H Schultz","year":"2021","journal-title":"N Engl J Med"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0140-6736(21)01693-7","article-title":"Very rare thrombosis with thrombocytopenia after second AZD1222 dose: a global safety database analysis","volume":"398","author":"P Bhuyan","year":"2021","journal-title":"Lancet"},{"issue":"24","key":"ref10","doi-asserted-by":"crossref","first-page":"2448","DOI":"10.1001\/jama.2021.7517","article-title":"US case reports of cerebral venous sinus thrombosis with thrombocytopenia after Ad26.COV2.S vaccination, March 2 to April 21, 2021","volume":"325","author":"I See","year":"2021","journal-title":"JAMA"},{"issue":"15","key":"ref11","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1056\/NEJMc2210813","article-title":"Vaccine-induced immune thrombocytopenia and thrombosis after the Sputnik V Vaccine","volume":"387","author":"R Herrera-Comoglio","year":"2022","journal-title":"N Engl J Med"},{"issue":"08","key":"ref12","doi-asserted-by":"crossref","first-page":"2710","DOI":"10.1182\/blood-2005-04-1546","article-title":"Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis","volume":"106","author":"N Martel","year":"2005","journal-title":"Blood"},{"issue":"20","key":"ref13","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1056\/NEJM199505183322003","article-title":"Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin","volume":"332","author":"T E Warkentin","year":"1995","journal-title":"N Engl J Med"},{"issue":"11","key":"ref14","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1111\/jth.15485","article-title":"To clot or not to clot? Ad is the question-Insights on mechanisms related to vaccine-induced thrombotic thrombocytopenia","volume":"19","author":"M Othman","year":"2021","journal-title":"J Thromb Haemost"},{"issue":"02","key":"ref15","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1053\/j.seminhematol.2022.02.002","article-title":"Epidemiology of VITT","volume":"59","author":"M Pai","year":"2022","journal-title":"Semin Hematol"},{"issue":"04","key":"ref16","doi-asserted-by":"crossref","first-page":"947","DOI":"10.3324\/haematol.2021.280154","article-title":"Comparative analysis of ChAdOx1 nCoV-19 and Ad26.COV2.S SARS-CoV-2 vector vaccines","volume":"107","author":"S Michalik","year":"2022","journal-title":"Haematologica"},{"issue":"18","key":"ref17","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1056\/NEJMoa2109908","article-title":"Clinical features of vaccine-induced immune thrombocytopenia and thrombosis","volume":"385","author":"S Pavord","year":"2021","journal-title":"N Engl J Med"},{"issue":"17","key":"ref18","doi-asserted-by":"crossref","first-page":"2720","DOI":"10.1182\/blood.2021015329","article-title":"Cerebral venous thrombosis due to vaccine-induced immune thrombotic thrombocytopenia after a second ChAdOx1 nCoV-19 dose","volume":"139","author":"K Krzywicka","year":"2022","journal-title":"Blood"},{"issue":"01","key":"ref19","first-page":"132","article-title":"Clinical features of heparin-induced thrombocytopenia including risk factors for thrombosis. A retrospective analysis of 408 patients","volume":"94","author":"A Greinacher","year":"2005","journal-title":"Thromb Haemost"},{"issue":"22","key":"ref20","doi-asserted-by":"crossref","first-page":"3360","DOI":"10.1182\/bloodadvances.2018024489","article-title":"American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia","volume":"2","author":"A Cuker","year":"2018","journal-title":"Blood Adv"},{"issue":"06","key":"ref21","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1097\/FJC.0b013e3181926928","article-title":"Risk factors for major bleeding in patients with heparin-induced thrombocytopenia treated with argatroban: a retrospective study","volume":"52","author":"M J Hursting","year":"2008","journal-title":"J Cardiovasc Pharmacol"},{"issue":"06","key":"ref22","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1055\/s-0037-1615946","article-title":"A comparison of danaparoid and lepirudin in heparin-induced thrombocytopenia","volume":"85","author":"B Farner","year":"2001","journal-title":"Thromb Haemost"},{"issue":"14","key":"ref23","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1161\/01.CIR.103.14.1838","article-title":"Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia","volume":"103","author":"B E Lewis","year":"2001","journal-title":"Circulation"},{"issue":"04","key":"ref24","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1111\/ijlh.13629","article-title":"Laboratory testing for suspected COVID-19 vaccine-induced (immune) thrombotic thrombocytopenia","volume":"43","author":"E J Favaloro","year":"2021","journal-title":"Int J Lab Hematol"},{"issue":"12","key":"ref25","doi-asserted-by":"crossref","first-page":"2896","DOI":"10.1111\/jth.15881","article-title":"Assessment of immunological anti-platelet factor 4 antibodies for vaccine-induced thrombotic thrombocytopenia (VITT) in a large Australian cohort: a multicenter study comprising 1284 patients","volume":"20","author":"E J Favaloro","year":"2022","journal-title":"J Thromb Haemost"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.ijid.2022.03.034","article-title":"Thrombosis patterns and clinical outcome of COVID-19 vaccine-induced immune thrombotic thrombocytopenia: a systematic review and meta-analysis","volume":"119","author":"A Y Kim","year":"2022","journal-title":"Int J Infect Dis"},{"issue":"06","key":"ref27","doi-asserted-by":"crossref","first-page":"245","DOI":"10.5694\/mja2.51229","article-title":"Australian and New Zealand approach to diagnosis and management of vaccine-induced immune thrombosis and thrombocytopenia","volume":"215","author":"V M Chen","year":"2021","journal-title":"Med J Aust"},{"key":"ref28","author":"National Institute for Health and Care Excellence","year":"2022"},{"issue":"05","key":"ref29","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1111\/imj.15783","article-title":"Understanding vaccine-induced thrombotic thrombocytopenia (VITT)","volume":"52","author":"C Dix","year":"2022","journal-title":"Intern Med J"},{"issue":"17","key":"ref30","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1056\/NEJM200104263441704","article-title":"Temporal aspects of heparin-induced thrombocytopenia","volume":"344","author":"T E Warkentin","year":"2001","journal-title":"N Engl J Med"},{"issue":"19","key":"ref31","first-page":"1883","article-title":"Heparin-induced thrombocytopenia","volume":"373","author":"A Greinacher","year":"2015","journal-title":"N Engl J Med"},{"issue":"07","key":"ref32","doi-asserted-by":"crossref","first-page":"502","DOI":"10.7326\/0003-4819-135-7-200110020-00009","article-title":"Delayed-onset heparin-induced thrombocytopenia and thrombosis","volume":"135","author":"T E Warkentin","year":"2001","journal-title":"Ann Intern Med"},{"issue":"03","key":"ref33","doi-asserted-by":"crossref","first-page":"210","DOI":"10.7326\/0003-4819-136-3-200202050-00009","article-title":"Delayed-onset heparin-induced thrombocytopenia","volume":"136","author":"L Rice","year":"2002","journal-title":"Ann Intern Med"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"117607","DOI":"10.1016\/j.jns.2021.117607","article-title":"Vaccine-induced immune thrombotic thrombocytopenia and cerebral venous sinus thrombosis post COVID-19 vaccination; a systematic review","volume":"428","author":"M Sharifian-Dorche","year":"2021","journal-title":"J Neurol Sci"},{"issue":"01","key":"ref35","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/(SICI)1096-8652(199709)56:1<12::AID-AJH3>3.0.CO;2-5","article-title":"Heparin-induced thrombocytopenia with thrombosis: incidence, analysis of risk factors, and clinical outcomes in 108 consecutive patients treated at a single institution","volume":"56","author":"S Nand","year":"1997","journal-title":"Am J Hematol"},{"issue":"05","key":"ref36","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/S0002-9343(96)00258-6","article-title":"A 14-year study of heparin-induced thrombocytopenia","volume":"101","author":"T E Warkentin","year":"1996","journal-title":"Am J Med"},{"issue":"12","key":"ref37","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1055\/a-1585-6182","article-title":"Venous thromboembolism and mild thrombocytopenia after ChAdOx1 nCoV-19 vaccination","volume":"121","author":"N Gabarin","year":"2021","journal-title":"Thromb Haemost"},{"issue":"03","key":"ref38","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1148\/radiol.220365","article-title":"Thrombus distribution in vaccine-induced immune thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination","volume":"305","author":"P Rogers","year":"2022","journal-title":"Radiology"},{"issue":"01","key":"ref39","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1055\/s-0038-1656329","article-title":"Platelet factor 4 complexed to heparin is the target for antibodies generated in heparin-induced thrombocytopenia","volume":"68","author":"J Amiral","year":"1992","journal-title":"Thromb Haemost"},{"issue":"11","key":"ref40","doi-asserted-by":"crossref","first-page":"3232","DOI":"10.1182\/blood.V83.11.3232.3232","article-title":"Immunoglobulin G from patients with heparin-induced thrombocytopenia binds to a complex of heparin and platelet factor 4","volume":"83","author":"J G Kelton","year":"1994","journal-title":"Blood"},{"issue":"03","key":"ref41","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1182\/blood.V72.3.925.bloodjournal723925","article-title":"Heparin-induced thrombocytopenia: laboratory studies","volume":"72","author":"J G Kelton","year":"1988","journal-title":"Blood"},{"issue":"21","key":"ref42","doi-asserted-by":"crossref","first-page":"2864","DOI":"10.1182\/blood-2016-11-709873","article-title":"Heparin-induced thrombocytopenia","volume":"129","author":"G M Arepally","year":"2017","journal-title":"Blood"},{"issue":"06","key":"ref43","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1002\/ajh.24006","article-title":"The platelet serotonin-release assay","volume":"90","author":"T E Warkentin","year":"2015","journal-title":"Am J Hematol"},{"issue":"11","key":"ref44","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1111\/jth.13813","article-title":"Autoimmune heparin-induced thrombocytopenia","volume":"15","author":"A Greinacher","year":"2017","journal-title":"J Thromb Haemost"},{"issue":"04","key":"ref45","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1056\/NEJMc2106383","article-title":"PF4 immunoassays in vaccine-induced thrombotic thrombocytopenia","volume":"385","author":"C Vayne","year":"2021","journal-title":"N Engl J Med"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s41586-021-03744-4","article-title":"Antibody epitopes in vaccine-induced immune thrombotic thrombocytopaenia","volume":"596","author":"A Huynh","year":"2021","journal-title":"Nature"},{"issue":"04","key":"ref47","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1182\/blood.2021012152","article-title":"Vaccine-induced immune thrombotic thrombocytopenia: what we know and do not know","volume":"138","author":"G M Arepally","year":"2021","journal-title":"Blood"},{"issue":"11","key":"ref48","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1182\/blood.2021012479","article-title":"The use of IV immunoglobulin in the treatment of vaccine-induced immune thrombotic thrombocytopenia","volume":"138","author":"G Uzun","year":"2021","journal-title":"Blood"},{"issue":"14","key":"ref49","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1182\/blood.2021012938","article-title":"Anti-platelet factor 4 antibodies causing VITT do not cross-react with SARS-CoV-2 spike protein","volume":"138","author":"A Greinacher","year":"2021","journal-title":"Blood"},{"issue":"15","key":"ref50","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1182\/blood.2022016474","article-title":"Vaccine-induced immune thrombotic thrombocytopenia is mediated by a stereotyped clonotypic antibody","volume":"140","author":"J J Wang","year":"2022","journal-title":"Blood"},{"issue":"16","key":"ref51","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.1182\/blood.2021014684","article-title":"Natural history of PF4 antibodies in vaccine-induced immune thrombocytopenia and thrombosis","volume":"139","author":"B Craven","year":"2022","journal-title":"Blood"},{"issue":"03","key":"ref52","doi-asserted-by":"crossref","first-page":"e12707","DOI":"10.1002\/rth2.12707","article-title":"Anti-platelet factor 4 immunoglobulin G levels in vaccine-induced immune thrombocytopenia and thrombosis: Persistent positivity through 7 months","volume":"6","author":"S J Montague","year":"2022","journal-title":"Res Pract Thromb Haemost"},{"issue":"10","key":"ref53","doi-asserted-by":"crossref","first-page":"3300","DOI":"10.1182\/blood.V97.10.3300","article-title":"Induction of monocyte tissue factor expression by antibodies to heparin-platelet factor 4 complexes developed in heparin-induced thrombocytopenia","volume":"97","author":"C Pouplard","year":"2001","journal-title":"Blood"},{"issue":"04","key":"ref54","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1182\/blood.V98.4.1252","article-title":"Antibodies from patients with heparin-induced thrombocytopenia stimulate monocytic cells to express tissue factor and secrete interleukin-8","volume":"98","author":"G M Arepally","year":"2001","journal-title":"Blood"},{"issue":"04","key":"ref55","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1161\/ATVBAHA.117.309846","article-title":"Tissue factor: an essential mediator of hemostasis and trigger of thrombosis","volume":"38","author":"S P Grover","year":"2018","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"22","key":"ref56","doi-asserted-by":"crossref","first-page":"5285","DOI":"10.1182\/blood-2011-06-359430","article-title":"PF4\/heparin-antibody complex induces monocyte tissue factor expression and release of tissue factor positive microparticles by activation of Fc\u03b3RI","volume":"119","author":"R S Kasthuri","year":"2012","journal-title":"Blood"},{"issue":"04","key":"ref57","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1182\/blood-2013-11-539262","article-title":"Platelet transactivation by monocytes promotes thrombosis in heparin-induced thrombocytopenia","volume":"127","author":"V Tutwiler","year":"2016","journal-title":"Blood"},{"issue":"23","key":"ref58","doi-asserted-by":"crossref","first-page":"5021","DOI":"10.1182\/blood-2010-03-276964","article-title":"Monocyte-bound PF4 in the pathogenesis of heparin-induced thrombocytopenia","volume":"116","author":"L Rauova","year":"2010","journal-title":"Blood"},{"issue":"01","key":"ref59","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1111\/bjh.17750","article-title":"Activation of circulating platelets in vaccine-induced thrombotic thrombocytopenia and its reversal by intravenous immunoglobulin","volume":"196","author":"J D McFadyen","year":"2022","journal-title":"Br J Haematol"},{"issue":"02","key":"ref60","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1002\/cyto.a.22647","article-title":"Microparticle analysis in disorders of hemostasis and thrombosis","volume":"89","author":"M J Mooberry","year":"2016","journal-title":"Cytometry A"},{"issue":"10","key":"ref61","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1161\/CIRCRESAHA.110.233056","article-title":"Microparticles in hemostasis and thrombosis","volume":"108","author":"A P Owens III","year":"2011","journal-title":"Circ Res"},{"issue":"11","key":"ref62","doi-asserted-by":"crossref","first-page":"3691","DOI":"10.1182\/blood.V84.11.3691.bloodjournal84113691","article-title":"Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia","volume":"84","author":"T E Warkentin","year":"1994","journal-title":"Blood"},{"issue":"01","key":"ref63","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1182\/blood.V96.1.188","article-title":"Morphological analysis of microparticle generation in heparin-induced thrombocytopenia","volume":"96","author":"M Hughes","year":"2000","journal-title":"Blood"},{"issue":"02","key":"ref64","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1002\/cyto.b.21507","article-title":"Activated platelet-derived and leukocyte-derived circulating microparticles and the risk of thrombosis in heparin-induced thrombocytopenia: a role for PF4-bearing microparticles?","volume":"94","author":"E Campello","year":"2018","journal-title":"Cytometry B Clin Cytom"},{"issue":"03","key":"ref65","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1007\/s11239-021-02505-4","article-title":"Procoagulant microparticles: a possible link between vaccine-induced immune thrombocytopenia (VITT) and cerebral sinus venous thrombosis","volume":"52","author":"B Marchandot","year":"2021","journal-title":"J Thromb Thrombolysis"},{"issue":"02","key":"ref66","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/bjh.18245","article-title":"Anti-severe acute respiratory syndrome coronavirus-2 adenoviral-vector vaccines trigger subclinical antiplatelet autoimmunity and increase of soluble platelet activation markers","volume":"198","author":"E Petito","year":"2022","journal-title":"Br J Haematol"},{"issue":"10","key":"ref67","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1056\/NEJM198703053161004","article-title":"Immune endothelial-cell injury in heparin-associated thrombocytopenia","volume":"316","author":"D B Cines","year":"1987","journal-title":"N Engl J Med"},{"issue":"02","key":"ref68","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1093\/intimm\/14.2.121","article-title":"Anti-platelet factor 4\/heparin antibodies from patients with heparin-induced thrombocytopenia provoke direct activation of microvascular endothelial cells","volume":"14","author":"M Blank","year":"2002","journal-title":"Int Immunol"},{"issue":"01","key":"ref69","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1172\/JCI116987","article-title":"Antibodies from patients with heparin-induced thrombocytopenia\/thrombosis are specific for platelet factor 4 complexed with heparin or bound to endothelial cells","volume":"93","author":"G P Visentin","year":"1994","journal-title":"J Clin Invest"},{"issue":"03","key":"ref70","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1172\/JCI90958","article-title":"Endothelial antigen assembly leads to thrombotic complications in heparin-induced thrombocytopenia","volume":"127","author":"V Hayes","year":"2017","journal-title":"J Clin Invest"},{"issue":"04","key":"ref71","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1097\/MBC.0b013e32806a8249","article-title":"Endothelial cell damage in heparin-induced thrombocytopenia","volume":"18","author":"S J Davidson","year":"2007","journal-title":"Blood Coagul Fibrinolysis"},{"issue":"15","key":"ref72","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1182\/blood.2018881607","article-title":"Recognition of PF4-VWF complexes by heparin-induced thrombocytopenia antibodies contributes to thrombus propagation","volume":"135","author":"I Johnston","year":"2020","journal-title":"Blood"},{"issue":"09","key":"ref73","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1161\/CIRCRESAHA.121.318902","article-title":"SARS-CoV-2 spike protein impairs endothelial function via downregulation of ACE 2","volume":"128","author":"Y Lei","year":"2021","journal-title":"Circ Res"},{"key":"ref74","doi-asserted-by":"crossref","first-page":"e74974","DOI":"10.7554\/eLife.74974","article-title":"Vaccine-induced COVID-19 mimicry syndrome","volume":"11","author":"E Kowarz","year":"2022","journal-title":"eLife"},{"issue":"07","key":"ref75","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.3324\/haematol.2021.280180","article-title":"Vaccine-induced immune thrombotic thrombocytopenia: a possible pathogenic role of ChAdOx1 nCoV-19 vaccine-encoded soluble SARS-CoV-2 spike protein","volume":"107","author":"M De Michele","year":"2022","journal-title":"Haematologica"},{"key":"ref76","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1182\/blood-2021-151685","article-title":"Vaccine-induced thrombocytopenia and thrombosis (VITT) antibodies recognize neutrophil-activating peptide 2 (NAP2) as well as platelet factor 4 (PF4): mechanistic and clinical implications","volume":"138","author":"L Rauova","year":"2021","journal-title":"Blood"},{"key":"ref78","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1126\/science.1092385","article-title":"Neutrophil extracellular traps kill bacteria","volume":"303","author":"V Brinkmann","year":"2004","journal-title":"Science"},{"issue":"01","key":"ref79","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1055\/s-0038-1677040","article-title":"Neutrophil extracellular traps in arterial and venous thrombosis","volume":"45","author":"E Laridan","year":"2019","journal-title":"Semin Thromb Hemost"},{"issue":"18","key":"ref80","doi-asserted-by":"crossref","first-page":"e99445","DOI":"10.1172\/jci.insight.99445","article-title":"Neutrophil accumulation and NET release contribute to thrombosis in HIT","volume":"3","author":"K Gollomp","year":"2018","journal-title":"JCI Insight"},{"issue":"01","key":"ref81","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1038\/s41467-019-09160-7","article-title":"Neutrophil activation and NETosis are the major drivers of thrombosis in heparin-induced thrombocytopenia","volume":"10","author":"J Perdomo","year":"2019","journal-title":"Nat Commun"},{"issue":"05","key":"ref82","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1093\/intimm\/dxz084","article-title":"Heparin induces neutrophil elastase-dependent vital and lytic NET formation","volume":"32","author":"P M Lelliott","year":"2020","journal-title":"Int Immunol"},{"issue":"23","key":"ref83","doi-asserted-by":"crossref","first-page":"5439","DOI":"10.1182\/bloodadvances.2020003093","article-title":"Inhibition of NADPH oxidase blocks NETosis and reduces thrombosis in heparin-induced thrombocytopenia","volume":"5","author":"H HL Leung","year":"2021","journal-title":"Blood Adv"},{"issue":"22","key":"ref84","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1182\/blood.2021013231","article-title":"Insights in ChAdOx1 nCoV-19 vaccine-induced immune thrombotic thrombocytopenia","volume":"138","author":"A Greinacher","year":"2021","journal-title":"Blood"},{"issue":"39","key":"ref85","doi-asserted-by":"crossref","first-page":"4064","DOI":"10.1093\/eurheartj\/ehab506","article-title":"Immune complexes, innate immunity, and NETosis in ChAdOx1 vaccine-induced thrombocytopenia","volume":"42","author":"S Holm","year":"2021","journal-title":"Eur Heart J"},{"issue":"01","key":"ref86","doi-asserted-by":"crossref","first-page":"5206","DOI":"10.1038\/s41467-022-32946-1","article-title":"NETosis and thrombosis in vaccine-induced immune thrombotic thrombocytopenia","volume":"13","author":"H HL Leung","year":"2022","journal-title":"Nat Commun"},{"issue":"01","key":"ref87","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/cr.2009.139","article-title":"Complement and its role in innate and adaptive immune responses","volume":"20","author":"J R Dunkelberger","year":"2010","journal-title":"Cell Res"},{"key":"ref88","doi-asserted-by":"crossref","first-page":"449","DOI":"10.3389\/fimmu.2019.00449","article-title":"Complement in the pathophysiology of the antiphospholipid syndrome","volume":"10","author":"S Chaturvedi","year":"2019","journal-title":"Front Immunol"},{"issue":"14","key":"ref89","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1056\/NEJM198010023031404","article-title":"Heparin-associated thrombocytopenia","volume":"303","author":"D B Cines","year":"1980","journal-title":"N Engl J Med"},{"issue":"21","key":"ref90","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1182\/blood.2020009487","article-title":"Complement mediates binding and procoagulant effects of ultralarge HIT immune complexes","volume":"138","author":"S Khandelwal","year":"2021","journal-title":"Blood"},{"issue":"11","key":"ref91","doi-asserted-by":"crossref","first-page":"e151092","DOI":"10.1172\/JCI151092","article-title":"Is complement the culprit behind COVID-19 vaccine-related adverse reactions?","volume":"131","author":"D C Mastellos","year":"2021","journal-title":"J Clin Invest"},{"key":"ref92","doi-asserted-by":"crossref","first-page":"102728","DOI":"10.1016\/j.jaut.2021.102728","article-title":"Consumption of complement in a 26-year-old woman with severe thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination","volume":"124","author":"M Cugno","year":"2021","journal-title":"J Autoimmun"},{"issue":"20","key":"ref93","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1182\/blood-2017-05-787259","article-title":"Procoagulant platelets: generation, function, and therapeutic targeting in thrombosis","volume":"130","author":"E O Agbani","year":"2017","journal-title":"Blood"},{"issue":"04","key":"ref94","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1111\/jth.15650","article-title":"Measurement of procoagulant platelets provides mechanistic insight and diagnostic potential in heparin-induced thrombocytopenia","volume":"20","author":"C SM Lee","year":"2022","journal-title":"J Thromb Haemost"},{"issue":"08","key":"ref95","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.3324\/haematol.2021.279000","article-title":"Antibody-mediated procoagulant platelets in SARS-CoV-2-vaccination associated immune thrombotic thrombocytopenia","volume":"106","author":"K Althaus","year":"2021","journal-title":"Haematologica"},{"issue":"23","key":"ref96","doi-asserted-by":"crossref","first-page":"3430","DOI":"10.1182\/blood.2021013839","article-title":"The interaction between anti-PF4 antibodies and anticoagulants in vaccine-induced thrombotic thrombocytopenia","volume":"139","author":"A Singh","year":"2022","journal-title":"Blood"},{"issue":"11","key":"ref97","doi-asserted-by":"crossref","first-page":"3494","DOI":"10.1182\/bloodadvances.2021006698","article-title":"A novel flow cytometry procoagulant assay for diagnosis of vaccine-induced immune thrombotic thrombocytopenia","volume":"6","author":"C SM Lee","year":"2022","journal-title":"Blood Adv"},{"issue":"08","key":"ref98","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1515\/cclm-2012-0081","article-title":"EDTA-dependent pseudothrombocytopenia: further insights and recommendations for prevention of a clinically threatening artifact","volume":"50","author":"G Lippi","year":"2012","journal-title":"Clin Chem Lab Med"},{"issue":"49","key":"ref99","doi-asserted-by":"crossref","first-page":"eabl8213","DOI":"10.1126\/sciadv.abl8213","article-title":"ChAdOx1 interacts with CAR and PF4 with implications for thrombosis with thrombocytopenia syndrome","volume":"7","author":"A T Baker","year":"2021","journal-title":"Sci Adv"},{"issue":"05","key":"ref100","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1182\/blood.2021014712","article-title":"Thrombocytopenia and splenic platelet-directed immune responses after IV ChAdOx1 nCov-19 administration","volume":"140","author":"L Nicolai","year":"2022","journal-title":"Blood"},{"issue":"03","key":"ref101","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1111\/jth.15604","article-title":"Thrombosis and thrombocytopenia after HPV vaccination","volume":"20","author":"S Johansen","year":"2022","journal-title":"J Thromb Haemost"}],"container-title":["Seminars in Thrombosis and Hemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0043-1761269.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T00:14:06Z","timestamp":1686615246000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0043-1761269"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,27]]},"references-count":100,"journal-issue":{"issue":"05","published-online":{"date-parts":[[2023,6,12]]},"published-print":{"date-parts":[[2023,7]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0043-1761269","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0094-6176","1098-9064"],"issn-type":[{"value":"0094-6176","type":"print"},{"value":"1098-9064","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,27]]}}}