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This strategy brings along high costs and high pressure which is not sustainable. Alternatively, P5 healthcare is proposed focusing on five key elements: prevention, personalization, prediction, participation, psychocognition, however, changes in current clinical care pathways are required, for which antithrombin deficiency is a prime example. Hereditary antithrombin deficiency (ATD) is a genetic disorder, for which screening is instigated after a thrombotic episode. Current diagnostic tests for ATD lack sensitivity and refinement to correctly classify patients, and generic treatments are prescribed. A molecular understanding of ATD through a molecular diagnostic test that analyzes all clinically relevant features of antithrombin is required. Here, clinically relevant molecular characteristics of antithrombin, the diversity of antithrombin (deficiency) in heath and disease, and the strengths and weaknesses of antithrombin tests are reviewed. A mass spectrometry test that molecularly characterizes a patients antithrombin proteoforms harbors the highest potential to improve the clinical pathway for ATD. Application of this MS\u2010based test in a future enhanced clinical pathway will improve patient management and outcome through molecular characterization of antithrombin and enables the promise of P5 healthcare for ATD.<\/jats:p>","DOI":"10.1002\/mas.21929","type":"journal-article","created":{"date-parts":[[2025,3,15]],"date-time":"2025-03-15T10:19:26Z","timestamp":1742033966000},"page":"745-768","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Antithrombin: Deficiency, Diversity, and the Future of Diagnostics"],"prefix":"10.1002","volume":"45","author":[{"given":"Mirjam","family":"Kruijt","sequence":"first","affiliation":[{"name":"Department of Clinical Chemistry and Laboratory Medicine Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christa M.","family":"Cobbaert","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Laboratory Medicine Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3737-3807","authenticated-orcid":false,"given":"L. 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