{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T22:09:26Z","timestamp":1779919766766,"version":"3.53.1"},"reference-count":33,"publisher":"Georg Thieme Verlag KG","issue":"04","license":[{"start":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000},"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":["Thromb Haemost"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hereditary antithrombin (AT) deficiency is a rare autosomal dominant disorder that predisposes to the development of recurrent venous thromboembolism (VTE). Diagnosis is based on the measurement of reduced AT activity in plasma. However, not all commercial AT activity assays are equally suited for diagnosis since they differ in sensitivity toward different AT mutations.<\/jats:p>\n                  <jats:p>The aim of this study was to compare the ability of commonly used AT activity assays to diagnose inherited antithrombin deficiency, with a focus on type II AT deficiencies. We used samples from genetically confirmed AT deficient subjects (n\u2009=\u200976) and from patients with request for AT activity measurement for diagnostic purposes (n\u2009=\u2009152). AT activity was measured with five commercial assays on three analyzers.<\/jats:p>\n                  <jats:p>All reagent\/analyzer combinations showed specificities varying from 87 to 100%, except for 1 assay (56.5% specificity). Diagnostic sensitivity varied widely between assays, from 36.8% to 100%. All reagent\u2013analyzer combinations correctly identified variants causing type I AT deficiencies but only one variant responsible for type II heparin binding site (HBS) deficiency: p.Arg79Cys. For one of the assays, we observed a large difference in sensitivity (82.9 versus 55.3%) toward antithrombin type II HBS variants depending on the coagulation analyzer on which it is performed, suggesting that incubation time of sample and substrate could be a crucial driver of the sensitivity toward variants causing type II antithrombin deficiency. Our results suggest that inherited antithrombin deficiency is probably underestimated and improved diagnostic strategies are mandatory.<\/jats:p>","DOI":"10.1055\/a-2628-4046","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T20:13:07Z","timestamp":1749154387000},"page":"405-417","source":"Crossref","is-referenced-by-count":1,"title":["Diagnostic Performance of Commercial Antithrombin Activity Assays: Do We Get What We Expect?"],"prefix":"10.1055","volume":"126","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2163-8778","authenticated-orcid":false,"given":"Christelle","family":"Orlando","sequence":"additional","affiliation":[{"name":"Department of Hematology, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Dr\u00e8ze","sequence":"additional","affiliation":[{"name":"Department of Hematology, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Evenepoel","sequence":"additional","affiliation":[{"name":"Department of Hematology, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Seneca","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Jochmans","sequence":"additional","affiliation":[{"name":"Department of Hematology, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"issue":"06","key":"ref1","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1111\/j.1365-2516.2008.01830.x","article-title":"Inherited antithrombin deficiency: a review","volume":"14","author":"M M Patnaik","year":"2008","journal-title":"Haemophilia"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.thromres.2018.07.008","article-title":"The genetics of antithrombin","volume":"169","author":"J Corral","year":"2018","journal-title":"Thromb Res"},{"issue":"01","key":"ref3","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/j.1365-2141.1994.tb04878.x","article-title":"Prevalence of antithrombin deficiency in the healthy population","volume":"87","author":"R C Tait","year":"1994","journal-title":"Br J Haematol"},{"issue":"04","key":"ref4","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1002\/ajh.2830450409","article-title":"Prevalence of antithrombin deficiency in healthy blood donors: a cross-sectional study","volume":"45","author":"P S Wells","year":"1994","journal-title":"Am J Hematol"},{"issue":"11","key":"ref5","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.5858\/2002-126-1326-AD","article-title":"Antithrombin deficiency: issues in laboratory diagnosis","volume":"126","author":"K Kottke-Marchant","year":"2002","journal-title":"Arch Pathol Lab Med"},{"issue":"01","key":"ref6","doi-asserted-by":"crossref","first-page":"e32","DOI":"10.1111\/bjh.16963","article-title":"Genotype-phenotype gradient of SERPINC1 variants in a single family reveals a severe compound antithrombin deficiency in a dead embryo","volume":"191","author":"C Bravo-P\u00e9rez","year":"2020","journal-title":"Br J Haematol"},{"issue":"07","key":"ref7","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1172\/JCI10489","article-title":"Complete antithrombin deficiency in mice results in embryonic lethality","volume":"106","author":"K Ishiguro","year":"2000","journal-title":"J Clin Invest"},{"issue":"04","key":"ref8","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1055\/s-0038-1625983","article-title":"Risk of venous thrombosis in antithrombin deficiency: a systematic review and Bayesian meta-analysis","volume":"44","author":"F N Croles","year":"2018","journal-title":"Semin Thromb Hemost"},{"issue":"01","key":"ref9","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/jth.14648","article-title":"Recommendations for clinical laboratory testing for antithrombin deficiency; communication from the SSC of the ISTH","volume":"18","author":"E M Van Cott","year":"2020","journal-title":"J Thromb Haemost"},{"issue":"03","key":"ref10","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/j.1751-553X.2011.01307.x","article-title":"The phenotypic and genetic assessment of antithrombin deficiency","volume":"33","author":"P C Cooper","year":"2011","journal-title":"Int J Lab Hematol"},{"issue":"S 01","key":"ref11","first-page":"S67","article-title":"Antithrombin deficiency and its laboratory diagnosis","volume":"48","author":"L Muszbek","year":"2010","journal-title":"Clin Chem Lab Med"},{"issue":"06","key":"ref12","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1016\/j.thromres.2015.03.013","article-title":"Antithrombin heparin binding site deficiency: a challenging diagnosis of a not so benign thrombophilia","volume":"135","author":"C Orlando","year":"2015","journal-title":"Thromb Res"},{"issue":"05","key":"ref13","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1309\/AJCPVY4Z9XZMFOTH","article-title":"The superiority of anti-FXa assay over anti-FIIa assay in detecting heparin-binding site antithrombin deficiency","volume":"140","author":"B Kov\u00e1cs","year":"2013","journal-title":"Am J Clin Pathol"},{"key":"ref14","first-page":"176","article-title":"European Parliament and Council Regulation (EU) 2017\/746 of 5 April 2017 on in vitro diagnostic medical devices","volume":"117","year":"2017","journal-title":"Off J Eur Union"},{"issue":"02","key":"ref15","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1160\/TH11-12-0875","article-title":"Deficiencies of antithrombin, protein C and protein S\u2014practical experience in genetic analysis of a large patient cohort","volume":"108","author":"M Caspers","year":"2012","journal-title":"Thromb Haemost"},{"issue":"05","key":"ref16","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"S Richards","year":"2015","journal-title":"Genet Med"},{"issue":"06","key":"ref17","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1136\/jcp.44.6.477","article-title":"Screening for heparin binding variants of antithrombin","volume":"44","author":"P L Harper","year":"1991","journal-title":"J Clin Pathol"},{"issue":"01","key":"ref18","doi-asserted-by":"crossref","first-page":"16734","DOI":"10.1038\/s41598-023-43941-x","article-title":"Comparison of antithrombin activity assays in detection of patients with heparin binding site antithrombin deficiency: systematic review and meta-analysis","volume":"13","author":"T Rojnik","year":"2023","journal-title":"Sci Rep"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.thromres.2017.10.023","article-title":"Clinical and laboratory characteristics of antithrombin deficiencies: a large cohort study from a single diagnostic center","volume":"160","author":"R Gindele","year":"2017","journal-title":"Thromb Res"},{"issue":"01","key":"ref20","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.thromres.2013.05.012","article-title":"Great discrepancy in antithrombin activity measured using five commercially available functional assays","volume":"132","author":"K Javela","year":"2013","journal-title":"Thromb Res"},{"issue":"10","key":"ref21","doi-asserted-by":"crossref","first-page":"4258","DOI":"10.1182\/blood-2006-08-040774","article-title":"Antithrombin Cambridge II (A384S): an underestimated genetic risk factor for venous thrombosis","volume":"109","author":"J Corral","year":"2007","journal-title":"Blood"},{"issue":"02","key":"ref23","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1160\/TH17-08-0568","article-title":"Activated factor X-based versus thrombin-based antithrombin testing in thrombophilia workup in the DOAC era","volume":"118","author":"H R\u00fchl","year":"2018","journal-title":"Thromb Haemost"},{"issue":"01","key":"ref24","first-page":"146","article-title":"Antithrombin Dublin (p.Val30Glu): a relatively common variant with moderate thrombosis risk of causing transient antithrombin deficiency","volume":"116","author":"J Navarro-Fern\u00e1ndez","year":"2016","journal-title":"Thromb Haemost"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/0014-5793(90)81530-2","article-title":"Antithrombin Rouen-IV 24 Arg\u2014-Cys. The amino-terminal contribution to heparin binding","volume":"266","author":"J Y Borg","year":"1990","journal-title":"FEBS Lett"},{"issue":"02","key":"ref26","doi-asserted-by":"crossref","first-page":"e118","DOI":"10.1016\/j.thromres.2013.06.001","article-title":"Antithrombin deficiency in three Japanese families: one novel and two reported point mutations in the antithrombin gene","volume":"132","author":"K Maruyama","year":"2013","journal-title":"Thromb Res"},{"issue":"03","key":"ref27","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1021\/bi030173b","article-title":"Roles of N-terminal region residues Lys11, Arg13, and Arg24 of antithrombin in heparin recognition and in promotion and stabilization of the heparin-induced conformational change","volume":"43","author":"S Schedin-Weiss","year":"2004","journal-title":"Biochemistry"},{"issue":"06","key":"ref28","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1172\/JCI116133","article-title":"Pleiotropic effects of antithrombin strand 1C substitution mutations","volume":"90","author":"D A Lane","year":"1992","journal-title":"J Clin Invest"},{"issue":"04","key":"ref29","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1160\/TH10-08-0538","article-title":"Molecular basis of antithrombin deficiency","volume":"105","author":"B Luxembourg","year":"2011","journal-title":"Thromb Haemost"},{"issue":"01","key":"ref30","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1111\/bjh.12842","article-title":"Clinical presentation and molecular basis of congenital antithrombin deficiency in children: a cohort study","volume":"166","author":"R Kumar","year":"2014","journal-title":"Br J Haematol"},{"issue":"19","key":"ref31","doi-asserted-by":"crossref","first-page":"e161430","DOI":"10.1172\/jci.insight.161430","article-title":"Full-length antithrombin frameshift variant with aberrant C-terminus causes endoplasmic reticulum retention with a dominant-negative effect","volume":"7","author":"C Bravo-P\u00e9rez","year":"2022","journal-title":"JCI Insight"},{"issue":"02","key":"ref32","first-page":"249","article-title":"Impact of the type of SERPINC1 mutation and subtype of antithrombin deficiency on the thrombotic phenotype in hereditary antithrombin deficiency","volume":"111","author":"B Luxembourg","year":"2014","journal-title":"Thromb Haemost"},{"issue":"06","key":"ref33","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1160\/TH16-08-0635","article-title":"Thrombotic risk according to SERPINC1 genotype in a large cohort of subjects with antithrombin inherited deficiency","volume":"117","author":"M Alhenc-Gelas","year":"2017","journal-title":"Thromb Haemost"},{"issue":"10","key":"ref34","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1111\/jth.12364","article-title":"Type II antithrombin deficiency caused by a founder mutation Pro73Leu in the Finnish population: clinical picture","volume":"11","author":"M Puurunen","year":"2013","journal-title":"J Thromb Haemost"}],"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2628-4046.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T23:37:58Z","timestamp":1774309078000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2628-4046"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,5]]},"references-count":33,"journal-issue":{"issue":"04","published-online":{"date-parts":[[2026,3,23]]},"published-print":{"date-parts":[[2026,4]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2628-4046","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,6,5]]},"published":{"date-parts":[[2025,6,5]]}}}