{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:04:36Z","timestamp":1792087476990,"version":"4.4.0"},"reference-count":68,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Lab Hematology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The prototypic anti\u2010platelet factor 4 (PF4) disorder\u2014heparin\u2010induced thrombocytopenia and thrombosis (HITT)\u2014features immunoglobulin G (IgG) class antibodies that activate platelets, monocytes, and neutrophils in a mainly heparin\u2010dependent fashion via Fc\u03b3 receptor\u2010dependent cellular activation. The identification in 2021 of an ultrarare HITT\u2010mimicking disorder, vaccine\u2010induced immune thrombocytopenia and thrombosis (VITT)\u2014triggered by two different adenoviral vector vaccines\u2014abruptly broadened the spectrum of recognized anti\u2010PF4 disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To classify platelet\u2010activating anti\u2010PF4 disorders, both HITT\/HITT\u2010like and VITT\/VITT\u2010like.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Literature was reviewed from the perspective of a researcher\u2010clinician involved in identifying novel anti\u2010PF4 disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Atypical presentations of HITT with proximate heparin triggers but which evince heparin\u2010independent platelet\u2010activating properties (\u201cautoimmune HITT\u201d) have been recognized since 2001; heparin\u2010independent platelet\u2010activating properties also characterize HITT\u2010mimicking disorders with undefined non\u2010heparin triggers (e.g., post\u2010knee replacement \u201cspontaneous HITT\u201d). Antibodies identical to those of (vaccine\u2010induced) VITT can rarely be triggered by natural adenovirus infection. HITT and VITT antibodies recognize different epitopes on PF4. All the aforementioned anti\u2010PF4 disorders are acute, transient, and self\u2010limited. Recently, however, chronic anti\u2010PF4 disorders featuring potent VITT\u2010like properties of monoclonal proteins (M\u2010proteins) have been identified: this oftentimes treatment\u2010refractory entity, named \u201cVITT\u2010like monoclonal gammopathy of thrombotic significance\u201d (VITT\u2010like MGTS), dramatically expands the clinical spectrum of recognized anti\u2010PF4 disorders. Anti\u2010PF4 disorders with heparin\u2010independent platelet\u2010activating antibodies, whether HITT or VITT, may require management strategies beyond anticoagulation alone, including high\u2010dose intravenous immunoglobulin (IVIG) or (for VITT\u2010like MGTS) the Bruton's tyrosine kinase inhibitor, ibrutinib.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Clinicians and laboratorians require knowledge of the rapidly broadening spectrum of recognized acute and chronic anti\u2010PF4 disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ijlh.14486","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T07:45:23Z","timestamp":1747122323000},"page":"259-271","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Classification of Platelet\u2010Activating Anti\u2010Platelet Factor 4 Disorders"],"prefix":"10.1111","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8046-7588","authenticated-orcid":false,"given":"Theodore E.","family":"Warkentin","sequence":"first","affiliation":[{"name":"Department of Pathology and Molecular Medicine McMaster University  Ontario Canada"},{"name":"Department of Medicine McMaster University  Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,13]]},"reference":[{"issue":"3","key":"e_1_2_13_2_1","first-page":"409","article-title":"Heparin\u2010Induced Thrombocytopenia With Thrombotic and Hemorrhagic Manifestations","volume":"136","author":"Rhodes G. 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