{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T03:27:10Z","timestamp":1792207630393,"version":"4.4.0"},"reference-count":36,"publisher":"American Society of Hematology","issue":"26","license":[{"start":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T00:00:00Z","timestamp":1698278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,12,28]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Platelet-activating anti-platelet factor 4 (PF4)\/heparin antibodies and anti-PF4 antibodies cause heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombocytopenia and thrombosis (VITT), respectively. Diagnostic and treatment considerations differ somewhat between HIT and VITT. We identified patients with thrombocytopenia and thrombosis without proximate heparin exposure or adenovirus-based vaccination who tested strongly positive by PF4\/polyanion enzyme-immunoassays and negative\/weakly positive by heparin-induced platelet activation (HIPA) test but strongly positive by PF4-induced platelet activation (PIPA) test (ie, VITT-like profile). We tested these patients by a standard chemiluminescence assay that detects anti-PF4\/heparin antibodies found in HIT (HemosIL AcuStar HIT-IgG(PF4-H)) as well as a novel chemiluminescence assay for anti-PF4 antibodies found in VITT. Representative control sera included an exploratory anti-PF4 antibody-positive but HIPA-negative\/weak cohort obtained before 2020 (n\u00a0= 188). We identified 9 patients with a clinical-pathological profile of a VITT-like disorder in the\u00a0absence of proximate heparin or vaccination, with a high frequency of stroke (arterial, n\u00a0= 3; cerebral venous sinus thrombosis, n\u00a0= 4), thrombocytopenia (median platelet count nadir, 49\u00a0\u00d7 109\/L), and hypercoagulability (greatly elevated D-dimer levels). VITT-like serological features included strong reactivity by PIPA (aggregation &amp;lt;10 minutes in 9\/9 sera) and positive testing in the novel anti-PF4 chemiluminescence assay (3\/9 also tested positive in the anti-PF4\/heparin chemiluminescence assay). Our exploratory cohort identified 13 additional patient sera obtained before 2020 with VITT-like anti-PF4 antibodies. Platelet-activating VITT-like anti-PF4 antibodies should be considered in patients with thrombocytopenia, thrombosis, and very high D-dimer levels, even without a proximate exposure to heparin or adenovirus vector vaccines.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2023022136","type":"journal-article","created":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T17:31:13Z","timestamp":1698341473000},"page":"2305-2314","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":72,"title":["Anti-PF4 immunothrombosis without proximate heparin or adenovirus vector vaccine exposure"],"prefix":"10.1182","volume":"142","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6660-9949","authenticated-orcid":false,"given":"Linda","family":"Sch\u00f6nborn","sequence":"first","affiliation":[{"name":"1Institut f\u00fcr Transfusionsmedizin, Universit\u00e4tsmedizin Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Esteban","sequence":"additional","affiliation":[{"name":"2Werfen, Lli\u00e7\u00e0 d\u2019Amunt, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5025-7355","authenticated-orcid":false,"given":"Jan","family":"Wesche","sequence":"additional","affiliation":[{"name":"1Institut f\u00fcr Transfusionsmedizin, Universit\u00e4tsmedizin Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Dobosz","sequence":"additional","affiliation":[{"name":"2Werfen, Lli\u00e7\u00e0 d\u2019Amunt, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Broto","sequence":"additional","affiliation":[{"name":"2Werfen, Lli\u00e7\u00e0 d\u2019Amunt, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5905-3607","authenticated-orcid":false,"given":"Sara Rovira","family":"Puig","sequence":"additional","affiliation":[{"name":"2Werfen, Lli\u00e7\u00e0 d\u2019Amunt, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Fuhrmann","sequence":"additional","affiliation":[{"name":"1Institut f\u00fcr Transfusionsmedizin, Universit\u00e4tsmedizin Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Torres","sequence":"additional","affiliation":[{"name":"2Werfen, Lli\u00e7\u00e0 d\u2019Amunt, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Serra","sequence":"additional","affiliation":[{"name":"2Werfen, Lli\u00e7\u00e0 d\u2019Amunt, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roser","family":"Llevadot","sequence":"additional","affiliation":[{"name":"2Werfen, Lli\u00e7\u00e0 d\u2019Amunt, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6173-6730","authenticated-orcid":false,"given":"Marta","family":"Palicio","sequence":"additional","affiliation":[{"name":"2Werfen, Lli\u00e7\u00e0 d\u2019Amunt, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0114-5570","authenticated-orcid":false,"given":"Jing Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"3Department of Immunology, College of Medicine and Public Health, Flinders University and SA Pathology, Bedford Park, SA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom Paul","family":"Gordon","sequence":"additional","affiliation":[{"name":"3Department of Immunology, College of Medicine and Public Health, Flinders University and SA Pathology, Bedford Park, SA, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edelgard","family":"Lindhoff-Last","sequence":"additional","affiliation":[{"name":"4Cardioangiology Center Bethanien Hospital, CCB Coagulation Center and CCB Coagulation Research Center, Frankfurt, Hessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Till","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"5Institute for Transplantation Diagnostics and Cell Therapeutics, University Hospital Duesseldorf, Medical Faculty, Duesseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9686-9920","authenticated-orcid":false,"given":"Lorenzo","family":"Alberio","sequence":"additional","affiliation":[{"name":"6Service and Central Laboratory of Hematology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Langer","sequence":"additional","affiliation":[{"name":"7Zentrum f\u00fcr Onkologie, II. Medizinische Klinik und Poliklinik, Universit\u00e4tsklinikum Eppendorf, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1369-418X","authenticated-orcid":false,"given":"Christian","family":"Boehme","sequence":"additional","affiliation":[{"name":"8Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenia","family":"Biguzzi","sequence":"additional","affiliation":[{"name":"9Clinic of Hematology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie","family":"Grosse","sequence":"additional","affiliation":[{"name":"10Department of Pediatrics, Dr. von Hauner Children\u2019s Hospital, Ludwig Maximilian University, Munich, 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