ArticleResearch and practice in thrombosis and haemostasis2023
Antithrombin diagnostics by mass spectrometry: Development and analytical validation of a next-generation test.
Article in Research and practice in thrombosis and haemostasis, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 11 citations in OpenAlex.
- Digital metrology in laboratory medicine: a call for bringing order to chaos to facilitate precision diagnostics.Clinical chemistry and laboratory medicine · 2025Article
- Amelioration of a von Willebrand disease type 2B phenotype in vivo upon treatment with allele-selective siRNAs.Blood advances · 2025Article
- Effects of sample matrix in the measurement of antithrombin by LC-MS: A role for immunocapture.Journal of mass spectrometry and advances in the clinical lab · 2023Article
- Antithrombin: Deficiency, Diversity, and the Future of Diagnostics.Mass spectrometry reviewsReview
- Hereditary Antithrombin Deficiency in Pediatric Patients: Pathophysiology, Clinical Features, Diagnosis, and Antithrombin Replacement Therapy.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisReview
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Authors and funding
4 authors at 1 institution in 1 country.
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Abstract
Background: Antithrombin deficiency is a rare but severe disorder leading to high risk of thrombosis. The current clinical care pathway relies on activity tests, which only provide overall functional information on the in vitro activity of antithrombin. However, antithrombin exists in many different forms, also known as proteoforms, with varying clinical phenotypes. Precision diagnostics, facilitated by mass spectrometry, provides a strategy to improve patient diagnostics by molecular characterization. Objectives: To develop and analytically validate a mass spectrometry-based test for molecular characterization of antithrombin. Methods: The test was analytically validated based on predefined analytical performance specifications. The validation covered imprecision, carryover, linearity, stability, analytical specificity, a provisional reference interval, and an explorative method comparison. Results: The test passed the predefined analytical performance specifications with a mean within-laboratory imprecision of 5.9%, linearity between 0.08 and 2.58 μmol/L, and a provisional reference interval of 1.07 to 1.49 μmol/L. When measuring samples with a suspected quantitative deficiency, the test showed a good correlation with a commercial activity test (Pearson Conclusion: The test passed the validation, and we now envision the use of the test for exploration of the clinical relevance of specific antithrombin proteoforms. Puzzling cases of antithrombin deficiency, for instance, due to ambiguous activity results or an atypical clinical presentation, can be investigated by the LC-MRM mass spectrometry test serving as an add-on to the activity test and providing a molecular diagnosis. Clinical studies are planned to investigate the potential of the test to improve antithrombin diagnostics. Furthermore, the molecular information gained using the test may aid in establishing better risk stratification and a basis for personalized medicine.
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