20.500.12556/DiRROS-31250 Bridging laboratory assays, genetics, and clinical phenotypes in antithrombin deficiency rethinking the diagnostic paradigm Background Diagnosis of antithrombin deficiency (ATD), the most severe inherited thrombophilia, commonly relies on functional assays despite their uncertain sensitivity. Moreover, routine characterization of ATD remains uncommon due to limited supporting clinical data. Objectives This study aimed to evaluate the diagnostic sensitivity of commercial antithrombin (AT) activity assays and assess clinical differences among ATD types to refine the current diagnostic approach. Methods Eighty-eight patients with decreased AT activity and 124 consecutive patients with unprovoked venous thromboembolism were included. AT activity was measured using six assays. Genetic analysis of SERPINC1 was performed by Sanger sequencing and multiplex ligation-dependent probe amplification; additionally, long-read whole-genome sequencing was conducted. Results Fifteen SERPINC1 variants were detected, including two novel ones. AT Padua I (p.Arg79His) was the most prevalent (49%). Sensitivity varied across AT activity assays, particularly for types IIRS and IIHBS, with variant-specific discrepancies. AT Dublin (p.Val30Glu), causing transient deficiency, was undetected by all assays. Two assays demonstrated very high sensitivity (93%; p < 0.001), while two others showed poor sensitivity (46%). Regardless of measured AT activity, characterization of ATD type enabled better risk stratification. Type I was associated with early-onset and recurrent venous thromboembolism, and type IIHBS was distinctly linked to arterial thrombosis. Conclusions Assay sensitivity varies considerably, and only a few proved suitable as first-line tests. Genetic testing for common variants undetectable by even the most sensitive assays, along with ATD characterization, should be integrated into diagnostic algorithms. Our results also suggest that young patients with arterial thrombosis should be screened for ATD. antithrombin iii deficiency blood coagulation tests mutation thrombophilia true false true Angleški jezik Ni določen Neznano 2026-07-23 11:32:59 2026-07-23 11:32:59 2026-07-24 03:52:01 0000-00-00 00:00:00 2026 0 0 Nasl. z nasl. zaslona; Opis vira z dne 11. 6. 2026; str. 1-10 Vol. 261, [article no.] 109689 May 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 61 1879-2472 10.1016/j.thromres.2026.109689 281250819 RAZ_Rojnik_Tamara_2026.pdf RAZ_Rojnik_Tamara_2026.pdf 1 3938E6B820AC81A4E7374FB040EB0400 6b017d8317a01476e02a9c8fdef21aff3f0b8215e0bc3f4929dbaf159f51dcfd 9abeb44e-8679-11f1-812a-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=48250 https://www.thrombosisresearch.com/article/S0049-3848(26)00108-8/fulltext 1 7f380e75-8679-11f1-812a-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=48249 Univerzitetni klinični center Ljubljana 0 0 0