{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:56:20Z","timestamp":1789991780022,"version":"4.0.1"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,11,6]],"date-time":"2019-11-06T00:00:00Z","timestamp":1572998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["201603PJT"],"award-info":[{"award-number":["201603PJT"]}],"id":[{"id":"10.13039\/501100000024","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":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Heparin\u2010induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by platelet\u2010activating anti\u2010platelet factor 4 (PF4)\/heparin antibodies. Pathogenic HIT antibodies can be detected by the serotonin\u2010release assay (SRA), a platelet activation test. We have regarded the SRA performed in our medical community (\u201cMcMaster\u201d SRA) as having high sensitivity and specificity. Recently, the concept of \u201cSRA\u2010negative HIT\u201d has been proposed for enzyme\u2010immunoassay (EIA)\u2010positive\/SRA\u2010negative patients with a HIT\u2010compatible clinical picture, who test positive in a PF4\u2010enhanced platelet activation assay. After identifying an index case of SRA\u2010negative HIT, we estimated the frequency of this condition by performing the \u201cPF4\u2010SRA\u201d (modified SRA using high concentrations of added PF4 rather than heparin) in EIA\u2010positive patients from a cohort study evaluating clinical and laboratory diagnosis of HIT. We defined SRA\u2010negative HIT as patients meeting three criteria: clinical picture compatible with HIT (4Ts\u2009\u2265\u20094 points); EIA\u2010positive (\u22651.00\u2009units); and PF4\u2010SRA\u2010positive. Among 430 patients, 35 were EIA\u2010positive\/SRA\u2010positive and 27 were EIA\u2010positive\/SRA\u2010negative. Among these 27 SRA\u2010negative patients, three were found to have subthreshold levels of platelet\u2010activating antibodies by PF4\u2010SRA, of whom one met clinical criteria for SRA\u2010negative HIT. Thus, based on identifying one patient with SRA\u2010negative HIT within a cohort study that found 35 SRA\u2010positive HIT patients, we estimate the sensitivity of the McMaster SRA for diagnosis of HIT to be 35\/36 (97.2%; 95% CI, 85.8\u201099.9%). Although the McMaster SRA is highly sensitive for HIT, occasional SRA\u2010negative but EIA\u2010positive patients strongly suspected of having HIT can have this diagnosis supported by a PF4\u2010enhanced activation assay such as the PF4\u2010SRA.<\/jats:p>","DOI":"10.1002\/ajh.25660","type":"journal-article","created":{"date-parts":[[2019,10,17]],"date-time":"2019-10-17T07:14:45Z","timestamp":1571296485000},"page":"38-47","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Serotonin\u2010release assay\u2010negative heparin\u2010induced thrombocytopenia"],"prefix":"10.1002","volume":"95","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 Michael G. DeGroote School of Medicine  Hamilton Ontario Canada"},{"name":"Department of Medicine Michael G. 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DeGroote School of Medicine  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"Kelton","sequence":"additional","affiliation":[{"name":"Department of Medicine Michael G. DeGroote School of Medicine  Hamilton Ontario Canada"},{"name":"McMaster Centre for Transfusion Research  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald M.","family":"Arnold","sequence":"additional","affiliation":[{"name":"Department of Medicine Michael G. DeGroote School of Medicine  Hamilton Ontario Canada"},{"name":"McMaster Centre for Transfusion Research  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,11,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.06-2109"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-11-012450"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-04-1546"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23127"},{"issue":"1","key":"e_1_2_7_6_1","first-page":"106","article-title":"Clinical and laboratory diagnosis of heparin\u2010induced thrombocytopenia: an integrated approach","volume":"40","author":"Cuker A","year":"2014","journal-title":"Semin Thromb 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