{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T14:58:55Z","timestamp":1792594735278,"version":"4.5.0"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,12,29]],"date-time":"2020-12-29T00:00:00Z","timestamp":1609200000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>IgG\u2010specific and polyspecific PF4\u2010dependent enzyme\u2010immunoassays (EIAs) have exceptionally high sensitivity (\u226599%) for diagnosis of heparin\u2010induced thrombocytopenia (HIT), a drug reaction caused by platelet\u2010activating antibodies detectable by serotonin\u2010release assay (SRA). The IgG\u2010specific EIAs are recommended for screening, as their high sensitivity is accompanied by relatively high specificity vis\u2010\u00e0\u2010vis polyspecific EIAs. We investigated the frequency of SRA\u2010positive\/EIA\u2010negative (SRA+\/EIA\u2212) HIT, prompted by referral to our reference HIT laboratory of serial blood samples from a patient (\u201cindex case\u201d) with false\u2010negative IgG\u2010specific EIAs. Despite initial clinical suspicion for HIT, repeat negative IgG\u2010specific EIAs prompted heparin resumption, which triggered recurrent thrombocytopenia and near\u2010fatal cardiac arrest, indicating likely post\u2010heparin HIT\u2010associated anaphylactoid reaction. Further investigations revealed a strong\u2010positive SRA, whether performed with heparin alone, PF4 alone, or PF4\/heparin, with inhibition by Fc receptor\u2010blocking monoclonal antibody (indicating IgG\u2010mediated platelet activation); however, five different IgG\u2010specific immunoassays yielded primarily negative (or weak\u2010positive) results. To investigate the frequency of SRA+\/EIA\u2212 HIT, we reviewed the laboratory and clinical features of patients with this serological profile during a 6\u2010year period in which our reference laboratory investigated for HIT using both SRA and IgG\u2010specific EIA. Although ~0.2% of 8546 patients had an SRA+\/EIA\u2212 profile, further review of 15 such cases indicated clerical\/laboratory misclassification or false\u2010positive SRA in all, with no SRA+\/EIA\u2212 HIT case identified. We conclude that while SRA+\/EIA\u2212 HIT is possible\u2014as shown by our index case\u2014this clinical picture is exceptionally uncommon. Moreover, the requirement for a positive EIA is a useful quality control maneuver that reduces risk of reporting a false\u2010positive SRA result.<\/jats:p>","DOI":"10.1002\/ajh.26075","type":"journal-article","created":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T02:40:20Z","timestamp":1608172820000},"page":"320-329","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Serotonin\u2010release assay\u2010positive but platelet factor 4\u2010dependent enzyme\u2010immunoassay negative: <scp>HIT<\/scp> or not <scp>HIT<\/scp>?"],"prefix":"10.1002","volume":"96","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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