{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T22:03:16Z","timestamp":1794002596974,"version":"4.8.0"},"reference-count":106,"publisher":"Georg Thieme Verlag KG","issue":"06","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Thromb Hemost"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombotic thrombocytopenia (VITT) are highly prothrombotic (thrombosis frequency \u226550%). Both are caused by platelet-activating anti-platelet factor 4 (PF4) antibodies, forming PF4\/IgG-containing immune complexes that engage platelet Fc\u03b3IIa receptors, producing strong platelet activation. In HIT, heparin crosslinks several PF4 molecules, whereas in VITT, anti-PF4 antibodies alone crosslink PF4. Sufficient levels of circulating anti-PF4 antibodies are needed to create the pathogenic immune complexes on platelet surfaces; this explains why certain serum (plasma)-based assays are highly sensitive for detecting HIT\/VITT antibodies. Accordingly, HIT and VITT are \u201cclinical-pathological\u201d disorders, that is, positive testing for such antibodies\u2014together with a compatible clinical picture\u2014is integral for diagnosis. Heparin (low concentrations) enhances HIT antibody-induced platelet activation, but platelet activation by VITT sera is usually inhibited by heparin. For both HIT and VITT, high sensitivity (&gt;99% and &gt;95%, respectively) characterizes PF4-dependent enzyme immunoassays (EIAs) and PF4-enhanced platelet activation assays; in contrast, certain rapid immunoassays have high sensitivity for HIT (&gt;90-97%) but poor sensitivity (&lt;25%) for VITT. HIT and VITT antibodies are directed at distinct sites on PF4: solid-phase EIAs and platelet activation assays are indifferent to these distinct antigen targets, but rapid immunoassays are not. We discuss a conceptual model where PF4 is viewed as a \u201cglobe,\u201d with the heparin-binding site the \u201cequator\u201d; in this model, HIT antibodies are primarily directed at antigen site(s) at the north and south \u201cpoles\u201d of PF4 (formed when PF4 binds to heparin), whereas VITT antibodies recognize sites on the equator.<\/jats:p>","DOI":"10.1055\/s-0042-1758818","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T00:02:55Z","timestamp":1669939375000},"page":"621-633","source":"Crossref","is-referenced-by-count":44,"title":["Laboratory Testing for Heparin-Induced Thrombocytopenia and Vaccine-Induced Immune Thrombotic Thrombocytopenia Antibodies: A Narrative Review"],"prefix":"10.1055","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8046-7588","authenticated-orcid":false,"given":"Theodore E.","family":"Warkentin","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada"},{"name":"Department of Medicine, McMaster University, Hamilton, Ontario, Canada"},{"name":"Transfusion Medicine, Hamilton Regional Laboratory Medicine Program, Hamilton, Ontario, Canada"},{"name":"Service of Benign Hematology, Hamilton Health Sciences, Hamilton General Hospital, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8343-7336","authenticated-orcid":false,"given":"Andreas","family":"Greinacher","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2022,12,1]]},"reference":[{"issue":"03","key":"ref1","first-page":"409","article-title":"Heparin induced thrombocytopenia with thrombotic and hemorrhagic manifestations","volume":"136","author":"G R Rhodes","year":"1973","journal-title":"Surg Gynecol Obstet"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1016\/S0140-6736(82)90106-4","article-title":"Heparin-induced thrombocytopenia: association of thrombotic complications with heparin-dependent IgG antibody that induces thromboxane synthesis in platelet aggregation","volume":"2","author":"B H Chong","year":"1982","journal-title":"Lancet"},{"issue":"01","key":"ref3","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1182\/blood.V67.1.27.27","article-title":"A diagnostic test for heparin-induced thrombocytopenia","volume":"67","author":"D Sheridan","year":"1986","journal-title":"Blood"},{"issue":"06","key":"ref4","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1055\/s-0038-1646493","article-title":"A rapid and sensitive test for diagnosing heparin-associated thrombocytopenia","volume":"66","author":"A Greinacher","year":"1991","journal-title":"Thromb Haemost"},{"issue":"01","key":"ref5","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"},{"issue":"02","key":"ref6","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1053\/j.seminhematol.2022.02.005","article-title":"Platelet-activating anti-PF4 disorders: an overview","volume":"59","author":"T E Warkentin","year":"2022","journal-title":"Semin Hematol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.thromres.2021.05.018","article-title":"Spontaneous HIT syndrome: knee replacement, infection, and parallels with vaccine-induced immune thrombotic thrombocytopenia","volume":"204","author":"T E Warkentin","year":"2021","journal-title":"Thromb Res"},{"issue":"01","key":"ref8","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3390\/antib11010007","article-title":"Antibodies against platelet factor 4 and their associated pathologies: from HIT\/HITT to spontaneous HIT-like syndrome, to COVID-19, to VITT\/TTS","volume":"11","author":"E J Favaloro","year":"2022","journal-title":"Antibodies (Basel)"},{"issue":"22","key":"ref9","first-page":"2092","article-title":"A prothrombotic thrombocytopenic disorder resembling heparin-induced thrombocytopenia following coronavirus-19 vaccination","volume":"384","author":"A Greinacher","year":"2021","journal-title":"N Engl J Med"},{"key":"ref10","first-page":"272","volume-title":"Laboratory testing for heparin-induced thrombocytopenia","author":"T E Warkentin","year":"2013"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1042\/bj3120357","article-title":"Heparin binding to platelet factor-4. An NMR and site-directed mutagenesis study: arginine residues are crucial for binding","volume":"312","author":"K H Mayo","year":"1995","journal-title":"Biochem J"},{"issue":"02","key":"ref12","first-page":"247","article-title":"Heparin-associated thrombocytopenia: isolation of the antibody and characterization of a multimolecular PF4-heparin complex as the major antigen","volume":"71","author":"A Greinacher","year":"1994","journal-title":"Thromb Haemost"},{"issue":"11","key":"ref13","doi-asserted-by":"crossref","first-page":"3232","DOI":"10.1182\/blood.V83.11.3232.3232","article-title":"Immunoglobulin G from patients with heparin-induced thrombocytopenia binds to a complex of heparin and platelet factor 4","volume":"83","author":"J G Kelton","year":"1994","journal-title":"Blood"},{"issue":"01","key":"ref14","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1172\/JCI116987","article-title":"Antibodies from patients with heparin-induced thrombocytopenia\/thrombosis are specific for platelet factor 4 complexed with heparin or bound to endothelial cells","volume":"93","author":"G P Visentin","year":"1994","journal-title":"J Clin Invest"},{"issue":"18","key":"ref15","doi-asserted-by":"crossref","first-page":"e99445","DOI":"10.1172\/jci.insight.99445","article-title":"Neutrophil accumulation and NET release contribute to thrombosis in HIT","volume":"3","author":"K Gollomp","year":"2018","journal-title":"JCI Insight"},{"issue":"01","key":"ref16","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1038\/s41467-019-09160-7","article-title":"Neutrophil activation and NETosis are the major drivers of thrombosis in heparin-induced thrombocytopenia","volume":"10","author":"J Perdomo","year":"2019","journal-title":"Nat Commun"},{"issue":"01","key":"ref17","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1182\/blood.2021014588","article-title":"Monoclonal and oligoclonal anti-platelet factor 4 antibodies mediate VITT","volume":"140","author":"A J Kanack","year":"2022","journal-title":"Blood"},{"issue":"17","key":"ref18","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1056\/NEJM200104263441704","article-title":"Temporal aspects of heparin-induced thrombocytopenia","volume":"344","author":"T E Warkentin","year":"2001","journal-title":"N Engl J Med"},{"issue":"11","key":"ref19","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1111\/jth.15826","article-title":"Temporal presentations of heparin-induced thrombocytopenia following cardiac surgery: a single-center, retrospective cohort study","volume":"20","author":"T E Warkentin","year":"2022","journal-title":"J Thromb Haemost"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"S92","DOI":"10.1002\/ajh.23127","article-title":"HITlights: a career perspective on heparin-induced thrombocytopenia","volume":"87","author":"T E Warkentin","year":"2012","journal-title":"Am J Hematol"},{"issue":"11","key":"ref21","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1111\/jth.13813","article-title":"Autoimmune heparin-induced thrombocytopenia","volume":"15","author":"A Greinacher","year":"2017","journal-title":"J Thromb Haemost"},{"issue":"07","key":"ref22","doi-asserted-by":"crossref","first-page":"502","DOI":"10.7326\/0003-4819-135-7-200110020-00009","article-title":"Delayed-onset heparin-induced thrombocytopenia and thrombosis","volume":"135","author":"T E Warkentin","year":"2001","journal-title":"Ann Intern Med"},{"issue":"05","key":"ref23","first-page":"813","article-title":"Clinical picture of heparin-induced thrombocytopenia (HIT) and its differentiation from non-HIT thrombocytopenia","volume":"116","author":"T E Warkentin","year":"2016","journal-title":"Thromb Haemost"},{"issue":"03","key":"ref24","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.chest.2017.03.050","article-title":"IVIg for treatment of severe refractory heparin-induced thrombocytopenia","volume":"152","author":"A Padmanabhan","year":"2017","journal-title":"Chest"},{"issue":"14","key":"ref25","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1182\/blood-2017-06-788679","article-title":"Autoimmune HIT due to apheresis catheter heparin flushes for stem cell harvesting before autotransplantation for myeloma","volume":"130","author":"H Mian","year":"2017","journal-title":"Blood"},{"issue":"05","key":"ref26","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1160\/TH07-06-0423","article-title":"Delayed-onset heparin-induced thrombocytopenia, venous thromboembolism, and cerebral venous thrombosis: a consequence of heparin \u201cflushes\u201d","volume":"98","author":"M A Refaai","year":"2007","journal-title":"Thromb Haemost"},{"issue":"01","key":"ref27","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1182\/blood-2014-06-580894","article-title":"Heparin-independent, PF4-dependent binding of HIT antibodies to platelets: implications for HIT pathogenesis","volume":"125","author":"A Padmanabhan","year":"2015","journal-title":"Blood"},{"issue":"01","key":"ref28","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1182\/bloodadvances.2016000877","article-title":"Polyphosphate\/platelet factor 4 complexes can mediate heparin-independent platelet activation in heparin-induced thrombocytopenia","volume":"1","author":"D B Cines","year":"2016","journal-title":"Blood Adv"},{"issue":"07","key":"ref29","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.amjmed.2008.03.012","article-title":"A spontaneous prothrombotic disorder resembling heparin-induced thrombocytopenia","volume":"121","author":"T E Warkentin","year":"2008","journal-title":"Am J Med"},{"issue":"09","key":"ref30","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1111\/j.1538-7836.2008.03040.x","article-title":"Fatal heparin-induced thrombocytopenia (HIT) during warfarin thromboprophylaxis following orthopedic surgery: another example of \u2018spontaneous\u2019 HIT?","volume":"6","author":"R M Jay","year":"2008","journal-title":"J Thromb Haemost"},{"issue":"05","key":"ref31","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.3324\/haematol.2021.280366","article-title":"Platelet-activating anti-PF4 antibodies mimic VITT antibodies in an unvaccinated patient with monoclonal gammopathy","volume":"107","author":"A Greinacher","year":"2022","journal-title":"Haematologica"},{"issue":"10","key":"ref32","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1160\/TH17-03-0212","article-title":"Platelet count recovery and seroreversion in immune HIT despite continuation of heparin: further observations and literature review","volume":"117","author":"A W Shih","year":"2017","journal-title":"Thromb Haemost"},{"issue":"06","key":"ref33","doi-asserted-by":"crossref","first-page":"e929","DOI":"10.1212\/CPJ.0000000000000805","article-title":"Spontaneous heparin-induced thrombocytopenia presenting as cerebral venous sinus thrombosis","volume":"11","author":"G Moores","year":"2021","journal-title":"Neurol Clin Pract"},{"issue":"22","key":"ref34","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1056\/NEJMoa2104840","article-title":"Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination","volume":"384","author":"A Greinacher","year":"2021","journal-title":"N Engl J Med"},{"issue":"22","key":"ref35","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1056\/NEJMoa2104882","article-title":"Thrombosis and thrombocytopenia after ChAdOx1 nCoV-19 vaccination","volume":"384","author":"N H Schultz","year":"2021","journal-title":"N Engl J Med"},{"issue":"23","key":"ref36","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1056\/NEJMoa2105385","article-title":"Pathologic antibodies to platelet factor 4 after ChAdOx1 nCoV-19 vaccination","volume":"384","author":"M Scully","year":"2021","journal-title":"N Engl J Med"},{"issue":"18","key":"ref37","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1056\/NEJMoa2109908","article-title":"Clinical features of vaccine-induced immune thrombocytopenia and thrombosis","volume":"385","author":"S Pavord","year":"2021","journal-title":"N Engl J Med"},{"issue":"04","key":"ref38","doi-asserted-by":"crossref","first-page":"513","DOI":"10.7326\/M21-4502","article-title":"Case series of thrombosis with thrombocytopenia syndrome after COVID-19 vaccination-United States, December 2020 to August 2021","volume":"175","author":"I See","year":"2022","journal-title":"Ann Intern Med"},{"issue":"15","key":"ref39","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1056\/NEJMc2210813","article-title":"Vaccine-induced immune thrombocytopenia and thrombosis after the Sputnik V vaccine","volume":"387","author":"R Herrera-Comoglio","year":"2022","journal-title":"N Engl J Med"},{"issue":"04","key":"ref41","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/M22-0118","article-title":"The epidemiology of thrombosis with thrombocytopenia syndrome: analogies with heparin-induced thrombocytopenia","volume":"175","author":"T E Warkentin","year":"2022","journal-title":"Ann Intern Med"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"100274","DOI":"10.1016\/j.lanepe.2021.100274","article-title":"Most cases of thrombosis and thrombocytopenia syndrome (TTS) post ChAdOx1 nCov-19 are vaccine-induced immune thrombotic thrombocytopenia (VITT)","volume":"12","author":"M Makris","year":"2021","journal-title":"Lancet Reg Health Eur"},{"issue":"02","key":"ref43","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1182\/bloodadvances.2022007336","article-title":"Characteristics of VITT antibodies in patients vaccinated with Ad26.COV2.S","volume":"7","author":"A Huynh","year":"2023","journal-title":"Blood Adv"},{"issue":"03","key":"ref44","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1111\/jth.15604","article-title":"Thrombosis and thrombocytopenia after HPV vaccination","volume":"20","author":"S Johansen","year":"2022","journal-title":"J Thromb Haemost"},{"issue":"03","key":"ref45","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1182\/blood.V91.3.916","article-title":"Antibodies from patients with heparin-induced thrombocytopenia\/thrombosis recognize different epitopes on heparin: platelet factor 4","volume":"91","author":"J S Suh","year":"1998","journal-title":"Blood"},{"issue":"09","key":"ref46","doi-asserted-by":"crossref","first-page":"3250","DOI":"10.1182\/blood.V92.9.3250","article-title":"Defining an antigenic epitope on platelet factor 4 associated with heparin-induced thrombocytopenia","volume":"92","author":"L Ziporen","year":"1998","journal-title":"Blood"},{"issue":"04","key":"ref47","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1182\/blood.V99.4.1230","article-title":"Defining a second epitope for heparin-induced thrombocytopenia\/thrombosis antibodies using KKO, a murine HIT-like monoclonal antibody","volume":"99","author":"Z Q Li","year":"2002","journal-title":"Blood"},{"key":"ref48","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"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s41586-021-03744-4","article-title":"Antibody epitopes in vaccine-induced immune thrombotic thrombocytopaenia","volume":"596","author":"A Huynh","year":"2021","journal-title":"Nature"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"14945","DOI":"10.1038\/ncomms14945","article-title":"Anti-platelet factor 4\/polyanion antibodies mediate a new mechanism of autoimmunity","volume":"8","author":"T H Nguyen","year":"2017","journal-title":"Nat Commun"},{"issue":"20","key":"ref51","doi-asserted-by":"crossref","first-page":"4963","DOI":"10.1182\/blood-2008-10-186064","article-title":"Studies of the immune response in heparin-induced thrombocytopenia","volume":"113","author":"T E Warkentin","year":"2009","journal-title":"Blood"},{"issue":"01","key":"ref52","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1182\/blood.V96.1.182","article-title":"Heparin-induced thrombocytopenia: new evidence for the dynamic binding of purified anti-PF4-heparin antibodies to platelets and the resultant platelet activation","volume":"96","author":"P M Newman","year":"2000","journal-title":"Blood"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/ijlh.12993","article-title":"Laboratory diagnosis of heparin-induced thrombocytopenia","volume":"41","author":"T E Warkentin","year":"2019","journal-title":"Int J Lab Hematol"},{"issue":"11","key":"ref54","doi-asserted-by":"crossref","first-page":"2579","DOI":"10.1111\/jth.15862","article-title":"Quantitative interpretation of PF4\/heparin-EIA optical densities in predicting platelet-activating VITT antibodies","volume":"20","author":"L Sch\u00f6nborn","year":"2022","journal-title":"J Thromb Haemost"},{"issue":"08","key":"ref55","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1111\/j.1538-7836.2007.02617.x","article-title":"Heparin-induced thrombocytopenia: a prospective study on the incidence, platelet-activating capacity and clinical significance of antiplatelet factor 4\/heparin antibodies of the IgG, IgM, and IgA classes","volume":"5","author":"A Greinacher","year":"2007","journal-title":"J Thromb Haemost"},{"issue":"08","key":"ref56","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 Haemost"},{"issue":"04","key":"ref57","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1182\/blood.2021012217","article-title":"Frequency of positive anti-PF4\/polyanion antibody tests after COVID-19 vaccination with ChAdOx1 nCoV-19 and BNT162b2","volume":"138","author":"T Thiele","year":"2021","journal-title":"Blood"},{"issue":"02","key":"ref58","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1111\/ijlh.13774","article-title":"Low clinical utility of testing for anti-platelet factor 4 in asymptomatic individuals after ChAdOx1 nCoV-19 vaccine","volume":"44","author":"A S Barefah","year":"2022","journal-title":"Int J Lab Hematol"},{"issue":"05","key":"ref59","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1056\/NEJM197607292950501","article-title":"Heparin-induced immune thrombocytopenia","volume":"295","author":"R B Babcock","year":"1976","journal-title":"N Engl J Med"},{"issue":"01","key":"ref60","first-page":"167","article-title":"Heparin immune thrombocytopenia: evidence for a heparin-platelet complex as the antigenic determinant","volume":"91","author":"D Green","year":"1978","journal-title":"J Lab Clin Med"},{"issue":"04","key":"ref61","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1001\/archinte.1978.03630280030014","article-title":"Heparin-induced thrombocytopenia","volume":"138","author":"J C Nelson","year":"1978","journal-title":"Arch Intern Med"},{"issue":"02","key":"ref62","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1182\/blood.V91.2.549","article-title":"Adenosine diphosphate (ADP) and ADP receptor play a major role in platelet activation\/aggregation induced by sera from heparin-induced thrombocytopenia patients","volume":"91","author":"J Polg\u00e1r","year":"1998","journal-title":"Blood"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1182\/asheducation-2011.1.143","article-title":"How I diagnose and manage HIT","volume":"2011","author":"T E Warkentin","year":"2011","journal-title":"Hematology (Am Soc Hematol Educ Program)"},{"issue":"06","key":"ref64","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":"04","key":"ref65","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1055\/s-0037-1614536","article-title":"First workshop for detection of heparin-induced antibodies: validation of the heparin-induced platelet-activation test (HIPA) in comparison with a PF4\/heparin ELISA","volume":"81","author":"P Eichler","year":"1999","journal-title":"Thromb Haemost"},{"issue":"10","key":"ref66","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1161\/01.ATV.0000238350.89477.88","article-title":"Close approximation of two platelet factor 4 tetramers by charge neutralization forms the antigens recognized by HIT antibodies","volume":"26","author":"A Greinacher","year":"2006","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"03","key":"ref67","first-page":"371","article-title":"Determinants of donor platelet variability when testing for heparin-induced thrombocytopenia","volume":"120","author":"T E Warkentin","year":"1992","journal-title":"J Lab Clin Med"},{"issue":"10","key":"ref68","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1111\/jth.13066","article-title":"Distinguishing between anti-platelet factor 4\/heparin antibodies that can and cannot cause heparin-induced thrombocytopenia","volume":"13","author":"I Nazi","year":"2015","journal-title":"J Thromb Haemost"},{"issue":"04","key":"ref69","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/ijlh.13031","article-title":"Timeline of heparin-induced thrombocytopenia seroconversion in serial plasma samples tested using an automated latex immunoturbidimetric assay","volume":"41","author":"T E Warkentin","year":"2019","journal-title":"Int J Lab Hematol"},{"issue":"01","key":"ref70","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1002\/ajh.25660","article-title":"Serotonin-release assay-negative heparin-induced thrombocytopenia","volume":"95","author":"T E Warkentin","year":"2020","journal-title":"Am J Hematol"},{"issue":"06","key":"ref71","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1002\/rth2.12348","article-title":"High-dose IVIG plus cangrelor platelet \u201canesthesia\u201d during urgent heparin-CPB in a patient with recent SRA-negative HIT-thrombosis with persisting platelet-activating antibodies","volume":"4","author":"A Koster","year":"2020","journal-title":"Res Pract Thromb Haemost"},{"issue":"06","key":"ref72","first-page":"1322","article-title":"A modified PF4-dependent, CD62p expression assay selectively detects serotonin-releasing antibodies in patients suspected of HIT","volume":"114","author":"A Padmanabhan","year":"2015","journal-title":"Thromb Haemost"},{"issue":"03","key":"ref73","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.chest.2016.02.641","article-title":"A novel PF4-dependent platelet activation assay identifies patients likely to have heparin-induced thrombocytopenia\/thrombosis","volume":"150","author":"A Padmanabhan","year":"2016","journal-title":"Chest"},{"issue":"05","key":"ref74","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1111\/bjh.14955","article-title":"Beneficial effect of exogenous platelet factor 4 for detecting pathogenic heparin-induced thrombocytopenia antibodies","volume":"179","author":"C Vayne","year":"2017","journal-title":"Br J Haematol"},{"issue":"01","key":"ref75","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/jth.15572","article-title":"Vaccine-induced immune thrombotic thrombocytopenia (VITT): update on diagnosis and management considering different resources","volume":"20","author":"A Greinacher","year":"2022","journal-title":"J Thromb Haemost"},{"issue":"12","key":"ref76","doi-asserted-by":"crossref","first-page":"2160","DOI":"10.1111\/j.1538-7836.2008.03171.x","article-title":"Heparin-induced thrombocytopenia\u2013therapeutic concentrations of danaparoid, unlike fondaparinux and direct thrombin inhibitors, inhibit formation of platelet factor 4-heparin complexes","volume":"6","author":"K Krauel","year":"2008","journal-title":"J Thromb Haemost"},{"issue":"02","key":"ref77","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1053\/j.seminhematol.2022.03.003","article-title":"Laboratory testing for VITT antibodies","volume":"59","author":"T E Warkentin","year":"2022","journal-title":"Semin Hematol"},{"issue":"26","key":"ref78","doi-asserted-by":"crossref","first-page":"3656","DOI":"10.1182\/blood.2021012064","article-title":"A flow cytometric assay to detect platelet-activating antibodies in VITT after ChAdOx1 nCov-19 vaccination","volume":"137","author":"S Handtke","year":"2021","journal-title":"Blood"},{"issue":"08","key":"ref79","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1056\/NEJMoa2107051","article-title":"Adjunct immune globulin for vaccine-induced immune thrombotic thrombocytopenia","volume":"385","author":"A Bourguignon","year":"2021","journal-title":"N Engl J Med"},{"issue":"04","key":"ref80","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1056\/NEJMc2106383","article-title":"PF4 immunoassays in vaccine-induced thrombotic thrombocytopenia","volume":"385","author":"C Vayne","year":"2021","journal-title":"N Engl J Med"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"100270","DOI":"10.1016\/j.lanepe.2021.100270","article-title":"Laboratory confirmed vaccine-induced immune thrombotic thrombocytopenia: retrospective analysis of reported cases after vaccination with ChAdOx-1 nCoV-19 in Germany","volume":"12","author":"T Thiele","year":"2022","journal-title":"Lancet Reg Health Eur"},{"issue":"11","key":"ref82","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1182\/blood.2021012479","article-title":"The use of IV immunoglobulin in the treatment of vaccine-induced immune thrombotic thrombocytopenia","volume":"138","author":"G Uzun","year":"2021","journal-title":"Blood"},{"issue":"22","key":"ref83","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1056\/NEJMc2112974","article-title":"Vaccine-induced thrombocytopenia with severe headache","volume":"385","author":"F Salih","year":"2021","journal-title":"N Engl J Med"},{"issue":"05","key":"ref84","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1002\/ajh.26488","article-title":"Persistence of Ad26.COV2.S-associated vaccine-induced immune thrombotic thrombocytopenia (VITT) and specific detection of VITT antibodies","volume":"97","author":"A J Kanack","year":"2022","journal-title":"Am J Hematol"},{"issue":"06","key":"ref85","doi-asserted-by":"crossref","first-page":"441","DOI":"10.3109\/09537104.2012.724736","article-title":"Heparin-induced multiple electrode aggregometry is a promising and useful functional tool for heparin-induced thrombocytopenia diagnosis: confirmation in a prospective study","volume":"24","author":"V Galea","year":"2013","journal-title":"Platelets"},{"issue":"12","key":"ref86","doi-asserted-by":"crossref","first-page":"2548","DOI":"10.1111\/jth.13516","article-title":"Heparin-induced multi-electrode aggregometry method for heparin-induced thrombocytopenia testing: communication from the SSC of the ISTH","volume":"14","author":"M C Morel-Kopp","year":"2016","journal-title":"J Thromb Haemost"},{"issue":"11","key":"ref87","doi-asserted-by":"crossref","first-page":"3494","DOI":"10.1182\/bloodadvances.2021006698","article-title":"A novel flow cytometry procoagulant assay for diagnosis of vaccine-induced immune thrombotic thrombocytopenia","volume":"6","author":"C SM Lee","year":"2022","journal-title":"Blood Adv"},{"issue":"04","key":"ref88","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1111\/jth.15650","article-title":"Measurement of procoagulant platelets provides mechanistic insight and diagnostic potential in heparin-induced thrombocytopenia","volume":"20","author":"C SM Lee","year":"2022","journal-title":"J Thromb Haemost"},{"issue":"04","key":"ref89","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1046\/j.1365-2141.2001.02869.x","article-title":"Determination of heparin-platelet factor 4-IgG antibodies improves diagnosis of heparin-induced thrombocytopenia","volume":"113","author":"E Lindhoff-Last","year":"2001","journal-title":"Br J Haematol"},{"issue":"01","key":"ref90","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1111\/j.1538-7836.2009.03645.x","article-title":"The use of well-characterized sera for the assessment of new diagnostic enzyme-immunoassays for the diagnosis of heparin-induced thrombocytopenia","volume":"8","author":"T E Warkentin","year":"2010","journal-title":"J Thromb Haemost"},{"issue":"05","key":"ref91","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1046\/j.1537-2995.1994.34594249047.x","article-title":"Laboratory diagnosis of heparin-associated thrombocytopenia and comparison of platelet aggregation test, heparin-induced platelet activation test, and platelet factor 4\/heparin enzyme-linked immunosorbent assay","volume":"34","author":"A Greinacher","year":"1994","journal-title":"Transfusion"},{"issue":"01","key":"ref92","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1046\/j.1365-2141.1996.d01-1876.x","article-title":"The epitope specificity of heparin-induced thrombocytopenia","volume":"95","author":"P Horsewood","year":"1996","journal-title":"Br J Haematol"},{"issue":"05","key":"ref93","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1055\/s-0038-1648491","article-title":"Heparin-associated thrombocytopenia: the antibody is not heparin specific","volume":"67","author":"A Greinacher","year":"1992","journal-title":"Thromb Haemost"},{"issue":"01","key":"ref94","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1067\/mlc.2001.115525","article-title":"Heparin is not required for detection of antibodies associated with heparin-induced thrombocytopenia\/thrombosis","volume":"138","author":"G P Visentin","year":"2001","journal-title":"J Lab Clin Med"},{"issue":"01","key":"ref95","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1160\/TH09-04-0253","article-title":"Effectiveness of a new immunoassay for the diagnosis of heparin-induced thrombocytopenia and improved specificity when detecting IgG antibodies","volume":"103","author":"C Pouplard","year":"2010","journal-title":"Thromb Haemost"},{"issue":"12","key":"ref96","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1055\/a-1535-9002","article-title":"PF4-dependent immunoassays in patients with vaccine-induced immune thrombotic thrombocytopenia: results of an interlaboratory comparison","volume":"121","author":"U J Sachs","year":"2021","journal-title":"Thromb Haemost"},{"issue":"08","key":"ref97","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1111\/jth.15362","article-title":"Evaluation of laboratory assays for anti-platelet factor 4 antibodies after ChAdOx1 nCOV-19 vaccination","volume":"19","author":"S Platton","year":"2021","journal-title":"J Thromb Haemost"},{"issue":"04","key":"ref98","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1111\/bjh.18022","article-title":"Vaccine-induced immune thrombocytopenia and thrombosis: the decline in anti-platelet factor 4 antibodies is assay-dependent","volume":"197","author":"S Platton","year":"2022","journal-title":"Br J Haematol"},{"issue":"02","key":"ref99","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1053\/j.seminhematol.2022.03.002","article-title":"Treatment of vaccine-induced immune thrombotic thrombocytopenia (VITT)","volume":"59","author":"N Gabarin","year":"2022","journal-title":"Semin Hematol"},{"issue":"12","key":"ref100","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1055\/a-1585-6182","article-title":"Venous thromboembolism and mild thrombocytopenia after ChAdOx1 nCoV-1 vaccination","volume":"121","author":"N Gabarin","year":"2021","journal-title":"Thromb Haemost"},{"issue":"01","key":"ref101","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3324\/haematol.2011.048074","article-title":"Rapid exclusion or confirmation of heparin-induced thrombocytopenia: a single-center experience with 1,291 patients","volume":"97","author":"V Nellen","year":"2012","journal-title":"Haematologica"},{"issue":"05","key":"ref102","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1111\/bjh.12939","article-title":"Prospective evaluation of a rapid nanoparticle-based lateral flow immunoassay (STic Expert(\u00ae) HIT) for the diagnosis of heparin-induced thrombocytopenia","volume":"166","author":"D Leroux","year":"2014","journal-title":"Br J Haematol"},{"key":"ref103","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.thromres.2017.03.010","article-title":"Performance characteristics of an automated latex immunoturbidimetric assay [HemosIL\u00ae HIT-Ab(PF4-H)] for the diagnosis of immune heparin-induced thrombocytopenia","volume":"153","author":"T E Warkentin","year":"2017","journal-title":"Thromb Res"},{"issue":"03","key":"ref104","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":"12","key":"ref105","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":"03","key":"ref106","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1055\/s-0040-1717078","article-title":"Characterization of new monoclonal PF4-specific antibodies as useful tools for studies on typical and autoimmune heparin-induced thrombocytopenia","volume":"121","author":"C Vayne","year":"2021","journal-title":"Thromb Haemost"},{"issue":"07","key":"ref107","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1182\/blood.V93.7.2149","article-title":"Antiprothrombin antibodies: detection and clinical significance in the antiphospholipid syndrome","volume":"93","author":"M Galli","year":"1999","journal-title":"Blood"}],"container-title":["Seminars in Thrombosis and Hemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0042-1758818.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T20:25:53Z","timestamp":1728505553000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0042-1758818"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,1]]},"references-count":106,"journal-issue":{"issue":"06","published-online":{"date-parts":[[2023,8,11]]},"published-print":{"date-parts":[[2023,9]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0042-1758818","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":[[2022,12,1]]}}}