{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:46:26Z","timestamp":1783039586384,"version":"3.54.6"},"reference-count":29,"publisher":"Georg Thieme Verlag KG","issue":"08","funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes for Health Research","doi-asserted-by":"crossref","award":["363046"],"award-info":[{"award-number":["363046"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Thromb Hemost"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Heparin-induced thrombocytopenia (HIT) is an autoimmune disorder caused by antibodies against platelet factor 4 (PF4) and heparin complexes. Rapid immunoassays (IAs) for detection of these antibodies mark a milestone in HIT diagnosis, despite a higher false-positive rate compared with functional platelet-activation assays. However, combining different rapid IAs may help to improve their diagnostic specificity. Here, we compared the individual performance of the latex immunoturbidimetric assay (LIA; HemosIL HIT-Ab [PF4-H]; sensitivity 91.7%, specificity 68.4%) and chemiluminescence immunoassay (CLIA; HemosIL AcuStarHIT-Ab [PF4-H]; sensitivity 92.4%, specificity 85.8%) with their combined performance using two unique diagnostic algorithms in a single prospective cohort of suspected HIT patients. Using the simultaneous algorithm adapted from Warkentin et al, the combined LIA\u2013CLIA had a sensitivity of 99.0% and specificity of 64.3%. The sequential algorithm adapted from Rittener-Ruff et al was applied in two theoretical scenarios to reflect real-world circumstances in diagnostic laboratories where access to clinical information is limited: (1) assuming all patients had an intermediate 4Ts score and (2) assuming all patients had a high 4Ts score. This algorithm correctly predicted HIT in 94.5% (high 4Ts) and 96.0% (intermediate 4Ts) and excluded HIT in 82.6% (high 4Ts) and 80.1% (intermediate 4Ts) of patients in either scenario, respectively. Although both combined algorithms improved diagnostic performance of individual IAs, the simultaneous algorithm showed fewer false predictions (7.9%) than the sequential algorithm (intermediate 4Ts: 37.6% and high 4Ts: 41.5%) and proved more practical as it does not rely on physician evaluations. Our findings highlight the importance of accounting for clinician and interlaboratory variability when evaluating diagnostic tests for HIT.<\/jats:p>","DOI":"10.1055\/s-0044-1786749","type":"journal-article","created":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T22:31:37Z","timestamp":1715466697000},"page":"1123-1130","source":"Crossref","is-referenced-by-count":7,"title":["Evaluating Diagnostic Algorithms for Heparin-Induced Thrombocytopenia using Two Combined Automated Rapid Immunoassays"],"prefix":"10.1055","volume":"50","author":[{"given":"Anna-Lise","family":"Bissola","sequence":"additional","affiliation":[{"name":"Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada"},{"name":"Michael G. DeGroote Centre for Transfusion Research, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada"},{"name":"Michael G. DeGroote Centre for Transfusion Research, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison","family":"Cranstone","sequence":"additional","affiliation":[{"name":"Michael G. DeGroote Centre for Transfusion Research, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane C.","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada"},{"name":"Michael G. DeGroote Centre for Transfusion Research, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore E.","family":"Warkentin","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada"},{"name":"Transfusion Medicine, Hamilton Regional Laboratory Medicine Program, Hamilton Health Sciences, 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, McMaster University, Hamilton, Ontario, Canada"},{"name":"Michael G. DeGroote Centre for Transfusion Research, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishac","family":"Nazy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada"},{"name":"Michael G. DeGroote Centre for Transfusion Research, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2024,5,11]]},"reference":[{"issue":"05","key":"ref1","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/S0002-9343(96)00258-6","article-title":"A 14-year study of heparin-induced thrombocytopenia","volume":"101","author":"T E Warkentin","year":"1996","journal-title":"Am J Med"},{"issue":"01","key":"ref2","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1055\/s-0038-1656329","article-title":"Platelet factor 4 complexed to heparin is the target for antibodies generated in heparin-induced thrombocytopenia","volume":"68","author":"J Amiral","year":"1992","journal-title":"Thromb Haemost"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"8277","DOI":"10.1038\/ncomms9277","article-title":"Atomic description of the immune complex involved in heparin-induced thrombocytopenia","volume":"6","author":"Z Cai","year":"2015","journal-title":"Nat Commun"},{"issue":"01","key":"ref4","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1182\/blood-2004-04-1544","article-title":"Ultralarge complexes of PF4 and heparin are central to the pathogenesis of heparin-induced thrombocytopenia","volume":"105","author":"L Rauova","year":"2005","journal-title":"Blood"},{"issue":"08","key":"ref5","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1182\/blood.V98.8.2442","article-title":"Heparin-induced thrombocytopenia\/thrombosis in a transgenic mouse model requires human platelet factor 4 and platelet activation through FcgammaRIIA","volume":"98","author":"M P Reilly","year":"2001","journal-title":"Blood"},{"issue":"05","key":"ref6","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1080\/09537109975960","article-title":"Generation of platelet-derived microparticles and procoagulant activity by heparin-induced thrombocytopenia IgG\/serum and other IgG platelet agonists: a comparison with standard platelet agonists","volume":"10","author":"T E Warkentin","year":"1999","journal-title":"Platelets"},{"issue":"05","key":"ref7","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/S0049-3848(00)00347-9","article-title":"Platelet activation and its role in thrombin generation in platelet-induced thrombin generation time","volume":"100","author":"P Radziwon","year":"2000","journal-title":"Thromb Res"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.thromres.2017.09.018","article-title":"PF4-HIT antibody (KKO) complexes activate broad innate immune and inflammatory responses","volume":"159","author":"L A Haile","year":"2017","journal-title":"Thromb Res"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/s41420-019-0188-0","article-title":"Platelet factor 4-containing immune complexes induce platelet activation followed by calpain-dependent platelet death","volume":"5","author":"T A Nevzorova","year":"2019","journal-title":"Cell Death Discov"},{"issue":"01","key":"ref10","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1161\/ATVBAHA.120.315445","article-title":"Heparin-induced thrombocytopenia: a focus on thrombosis","volume":"41","author":"G M Arepally","year":"2021","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"03","key":"ref11","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1182\/blood.V96.3.846","article-title":"Heparin-induced thrombocytopenia with thromboembolic complications: meta-analysis of 2 prospective trials to assess the value of parenteral treatment with lepirudin and its therapeutic aPTT 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Res"},{"issue":"12","key":"ref21","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1182\/blood-2018-04-847483","article-title":"High sensitivity and specificity of an automated IgG-specific chemiluminescence immunoassay for diagnosis of HIT","volume":"132","author":"T E Warkentin","year":"2018","journal-title":"Blood"},{"issue":"10","key":"ref22","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1111\/jth.15811","article-title":"Combinations of rapid immunoassays for a speedy diagnosis of heparin-induced thrombocytopenia","volume":"20","author":"L Rittener-Ruff","year":"2022","journal-title":"J Thromb Haemost"},{"issue":"08","key":"ref23","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1111\/j.1538-7836.2008.03025.x","article-title":"Quantitative interpretation of optical density measurements using PF4-dependent enzyme-immunoassays","volume":"6","author":"T E Warkentin","year":"2008","journal-title":"J Thromb 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Nagler","year":"2016","journal-title":"Blood"},{"issue":"06","key":"ref27","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1002\/ajh.24006","article-title":"The platelet serotonin-release assay","volume":"90","author":"T E Warkentin","year":"2015","journal-title":"Am J Hematol"},{"issue":"03","key":"ref28","doi-asserted-by":"crossref","first-page":"e85","DOI":"10.1016\/j.thromres.2013.01.005","article-title":"Evaluation of automated immunoassays in the diagnosis of heparin induced thrombocytopenia","volume":"131","author":"K Althaus","year":"2013","journal-title":"Thromb Res"},{"issue":"06","key":"ref29","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1111\/jth.13692","article-title":"Diagnostic accuracy of IgG-specific versus polyspecific enzyme-linked immunoassays in heparin-induced thrombocytopenia: a systematic review and meta-analysis","volume":"15","author":"H D Husseinzadeh","year":"2017","journal-title":"J Thromb Haemost"}],"container-title":["Seminars in Thrombosis and Hemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0044-1786749.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T10:13:41Z","timestamp":1730801621000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0044-1786749"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,11]]},"references-count":29,"journal-issue":{"issue":"08","published-online":{"date-parts":[[2024,10,11]]},"published-print":{"date-parts":[[2024,11]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0044-1786749","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0094-6176","1098-9064"],"issn-type":[{"value":"0094-6176","type":"print"},{"value":"1098-9064","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,11]]}}}