{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T13:43:31Z","timestamp":1792763011875,"version":"4.5.0"},"reference-count":27,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:00:00Z","timestamp":1777680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:00:00Z","timestamp":1777680000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL147734"],"award-info":[{"award-number":["HL147734"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL158932"],"award-info":[{"award-number":["HL158932"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL171911"],"award-info":[{"award-number":["HL171911"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL148120"],"award-info":[{"award-number":["HL148120"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL167668"],"award-info":[{"award-number":["HL167668"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL130724"],"award-info":[{"award-number":["HL130724"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Platelet factor 4\u2010polyanion enzyme\u2010linked immunosorbent assays (ELISAs) are considered highly sensitive for diagnosing heparin\u2010induced thrombocytopenia (HIT), such that current practice guidelines recommend use of ELISA\u2010negative results to exclude HIT. Once HIT is ruled out, alternative, non\u2010heparin\u2010based anticoagulant treatments are ceased, and heparin reintroduction frequently occurs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Antigen\u2010based and PF4\u2010dependent functional testing were used to study PF4\/polyvinylsulfonate ELISA\u2010negative platelet\u2010activating antibodies in HIT\u2010suspected patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Three patients with clinical presentations consistent with HIT tested negative in an ELISA using PF4\u2010polyvinylsulfonate (PF4\/PVS), an antigenic target very commonly used for HIT antibody screening. All three patients demonstrated PF4\u2010dependent platelet activation in functional testing that was sensitive to blockade of platelet Fc\u03b3RIIa receptors and inhibited by high concentrations of heparin, consistent with pathogenic HIT antibodies. Functional testing\u2010based screening of 500 ELISA\u2010negative patients identified three additional patients whose sera activated platelets in a PF4\u2010 and Fc\u03b3RIIa\u2010dependent manner and had clinical histories consistent with HIT. Five of the six ELISA\u2010negative HIT patients were re\u2010exposed to heparin, which precipitated a decrease in platelet counts in all re\u2010exposed patients, and one patient developed a new thrombus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Recognition of ELISA\u2010negative HIT is critical to avoid harm due to the cessation of alternative anticoagulation therapy and re\u2010exposure of these patients to heparin.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ajh.70333","type":"journal-article","created":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T07:41:16Z","timestamp":1777707676000},"page":"1790-1798","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pathogenic\n                    <scp>PF4<\/scp>\n                    \/Polyanion\n                    <scp>ELISA<\/scp>\n                    \u2010Negative Antibodies in\n                    <scp>HIT<\/scp>"],"prefix":"10.1002","volume":"101","author":[{"given":"Adam J.","family":"Kanack","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah P.","family":"Splinter","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily E.","family":"Mauch","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leben","family":"Tefera","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Cleveland Clinic  Cleveland Ohio 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