{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T04:05:17Z","timestamp":1793160317821,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T00:00:00Z","timestamp":1712707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vox Sanguinis"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Objectives<\/jats:title><jats:p>Vaccine\u2010induced thrombotic thrombocytopenia (VITT) is a rare adverse effect characterized by thrombocytopenia and thrombosis occurring after COVID\u201019 vaccination. VITT pathophysiology is not fully unravelled but shows similarities to heparin\u2010induced thrombocytopenia (HIT). HIT is characterized by the presence of antibodies against platelet factor 4 (PF4)\/heparin complex, which can activate platelets in an Fc\u03b3RIIa\u2010dependent manner, whereas IgG\u2010antibodies directed against PF4 play an important role in VITT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>We characterized all clinically suspected VITT cases in the Netherlands from a diagnostic perspective and hypothesized that patients who developed both thrombocytopenia and thrombosis display underlying mechanisms similar to those in HIT. We conducted an anti\u2010PF4 ELISA and a functional PF4\u2010induced platelet activation assay (PIPAA) with and without blocking the platelet\u2010Fc\u03b3RIIa and found positivity in both tests, suggesting VITT with mechanisms similar to those in VITT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 65 patients with both thrombocytopenia and thrombosis among 275 clinically suspected VITT cases. Of these 65 patients, 14 (22%) tested positive for anti\u2010PF4 and PF4\u2010dependent platelet activation. The essential role of platelet\u2010Fc\u03b3RIIa in VITT with mechanisms similar to those in HIT was evident, as platelet activation was inhibited by an Fc\u03b3RIIa\u2010blocking antibody in all 14 patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study shows that only a small proportion of clinically suspected VITT patients with thrombocytopenia and thrombosis have anti\u2010PF4\u2010inducing, Fc\u0263RIIa\u2010dependent platelet activation, suggesting an HIT\u2010like pathophysiology. This leaves the possibility for the presence of another type of pathophysiology (\u2018non\u2010HIT like\u2019) leading to VITT. More research on pathophysiology is warranted to improve the diagnostic algorithm and to identify novel therapeutic and preventive strategies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/vox.13633","type":"journal-article","created":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T08:43:21Z","timestamp":1712738601000},"page":"728-736","source":"Crossref","is-referenced-by-count":6,"title":["Laboratory approach for vaccine\u2010induced thrombotic thrombocytopenia diagnosis in the Netherlands"],"prefix":"10.1111","volume":"119","author":[{"given":"Romy T.","family":"Meier","sequence":"first","affiliation":[{"name":"Department of Experimental Immunohematology Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leendert","family":"Porcelijn","sequence":"additional","affiliation":[{"name":"Department of Immunohematology Diagnostics Sanquin Diagnostic Services  Sanquin The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Hofstede\u2010van Egmond","sequence":"additional","affiliation":[{"name":"Department of Immunohematology Diagnostics Sanquin Diagnostic Services  Sanquin The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne M. C.","family":"Henskens","sequence":"additional","affiliation":[{"name":"Central Diagnostic Laboratory Maastricht University Medical Centre  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M.","family":"Coutinho","sequence":"additional","affiliation":[{"name":"Department of Neurology Amsterdam UMC  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke J. H. A.","family":"Kruip","sequence":"additional","affiliation":[{"name":"Department of Haematology Erasmus University Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An K.","family":"Stroobants","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaap J.","family":"Zwaginga","sequence":"additional","affiliation":[{"name":"Department of Hematology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna G.","family":"van der Bom","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8065-3540","authenticated-orcid":false,"given":"C. Ellen","family":"van der Schoot","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunohematology Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7044-0525","authenticated-orcid":false,"given":"Masja","family":"de Haas","sequence":"additional","affiliation":[{"name":"Department of Immunohematology Diagnostics Sanquin Diagnostic Services  Sanquin The Netherlands"},{"name":"Department of Hematology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1608-876X","authenticated-orcid":false,"given":"Rick","family":"Kapur","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunohematology Sanquin Research and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2105385"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2104840"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2104882"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2105869"},{"key":"e_1_2_9_6_1","unstructured":"Figures on the COVID\u201019 vaccination programme | RIVM. Available from:https:\/\/www.rivm.nl\/en\/covid-19-vaccination\/figures-vaccination-programme. Last accessed 17 Jan 2023."},{"key":"e_1_2_9_7_1","unstructured":"Rijksoverheid.Vaccinaties | Coronadashboard | Rijksoverheid.nl.2022Available from:https:\/\/coronadashboard.rijksoverheid.nl\/landelijk\/vaccinaties. Last accessed 11 Feb 2022."},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2109908"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03744-4"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp1411910"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.120.315445"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-11-709873"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-019-0188-0"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1646493"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15341"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2107051"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15362"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2024.01.045"},{"key":"e_1_2_9_19_1","unstructured":"Leidraad trombocytopenie met of zonder trombose na COVID\u201019 vaccinatie | Federatie Medisch Specialisten. Available from:https:\/\/demedischspecialist.nl\/nieuwsoverzicht\/nieuws\/leidraad\u2010trombocytopenie\u2010met\u2010zonder\u2010trombose\u2010na\u2010covid\u201019\u2010vaccinatie. Last accessed 10 Feb 2022."},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26488"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023022136"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.13066"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.15862"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2022.02.002"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.artmed.2010.04.006"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021006379"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.122.060785"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms221910791"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.74974"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021013231"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1186000"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2021-151685"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023020872"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2021-001902"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/09537104.2022.2042238"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2008.03263.x"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2021.05.018"},{"key":"e_1_2_9_38_1","unstructured":"ChenRT BrightonC BlackS.Updated Proposed Brighton Collaboaration process for developing a standard case definition for study of new clinical syndrome X as applied to Thrombosis with Thrombocytopenia Syndrome (TTS).2021Available from:https:\/\/brightoncollaboration.us\/wp\u2010content\/uploads\/2021\/05\/TTS\u2010Interim\u2010Case\u2010Definition\u2010v10.16.3\u2010May\u201023\u20102021.pdf. Last accessed Mar 30 2024."},{"key":"e_1_2_9_39_1","unstructured":"Guidance for clinical case management of TTS following vaccination to prevent COVID\u201019. Available from:https:\/\/www.who.int\/publications\/i\/item\/9789240061989. Last accessed Mar 11 2024."},{"key":"e_1_2_9_40_1","first-page":"12","article-title":"Laboratory confirmed vaccine\u2010induced immune thrombotic thrombocytopenia: retrospective analysis of reported cases after vaccination with ChAdOx\u20101 nCoV\u201019 in Germany","volume":"12","author":"Thiele T","year":"2022","journal-title":"Lancet Reg Health Eur"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2106383"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.18022"}],"container-title":["Vox Sanguinis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/vox.13633","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T06:42:06Z","timestamp":1720593726000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/vox.13633"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,10]]},"references-count":41,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1111\/vox.13633"],"URL":"https:\/\/doi.org\/10.1111\/vox.13633","archive":["Portico"],"relation":{},"ISSN":["0042-9007","1423-0410"],"issn-type":[{"value":"0042-9007","type":"print"},{"value":"1423-0410","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,10]]}}}