Analytical dilemmas in lupus anticoagulant detection
Accurate lupus anticoagulant (LA) detection is crucial to antiphospholipid syndrome (APS) diagnosis. Detection is based on LA functional behavior in coagulation assays irrespective of epitope specificity. LA screening tests employ dilute phospholipids to accentuate in vitro inhibition by LAs, althou...
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| Format: | Article |
| Language: | English |
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Open Exploration Publishing Inc.
2023-08-01
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| Series: | Exploration of Immunology |
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| Online Access: | https://www.explorationpub.com/Journals/ei/Article/1003104 |
| _version_ | 1797691852372049920 |
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| author | Gary W. Moore |
| author_facet | Gary W. Moore |
| author_sort | Gary W. Moore |
| collection | DOAJ |
| description | Accurate lupus anticoagulant (LA) detection is crucial to antiphospholipid syndrome (APS) diagnosis. Detection is based on LA functional behavior in coagulation assays irrespective of epitope specificity. LA screening tests employ dilute phospholipids to accentuate in vitro inhibition by LAs, although they are not LA-specific and can be elevated by other coagulation abnormalities. Elevated screening tests are reflexed to mixing tests to distinguish between factor deficiency and inhibition. Confirmatory tests with high phospholipid concentration swamp LA to generate shorter clotting times than screening tests, whilst prolongation persists with non-phospholipid-dependent inhibitors. LA heterogeneity means that no single screening test detects every LA and the screen/mix/confirm medley must be applied to at least two assay types, usually dilute Russell’s viper venom time (dRVVT) and an LA-sensitive activated partial thromboplastin time (aPTT). Most laboratories restrict LA testing to these two assays, yet others, such as dilute prothrombin time (dPT), can perform with equal diagnostic efficacy, and additionally detect LA unreactive with dRVVT and aPTT. Converting clotting times to normalized ratios improves assay performance, and practitioners must choose between normal pooled plasma (NPP) clotting time denominators to reflect on-the-day assay performance, or reference interval (RI) mean clotting times to negate the effects of NPP variation. Cut-offs can be generated parametrically from normally distributed data, or different percentiles applied depending on the preferred balance between sensitivity and specificity. Sourcing sufficient donors for accurate cut-off estimations is problematic and transference exercises can be undertaken on low donor numbers. Analytical limitations of mixing tests have led to the adoption of alternative algorithms to the screen/mix/confirm test order, whilst some continue to rigidly apply the latter despite those limitations. Strategies to reduce or eliminate the effects of therapeutic anticoagulation have limitations, whilst the Taipan snake venom time (TSVT) screening test with an ecarin time (ET) confirmatory test is insensitive to vitamin K antagonist (VKA) and direct activated factor X anticoagulation. |
| first_indexed | 2024-03-12T02:19:20Z |
| format | Article |
| id | doaj.art-822bb8fc6a7846fba4268c1eb122d153 |
| institution | Directory Open Access Journal |
| issn | 2768-6655 |
| language | English |
| last_indexed | 2024-03-12T02:19:20Z |
| publishDate | 2023-08-01 |
| publisher | Open Exploration Publishing Inc. |
| record_format | Article |
| series | Exploration of Immunology |
| spelling | doaj.art-822bb8fc6a7846fba4268c1eb122d1532023-09-06T06:21:00ZengOpen Exploration Publishing Inc.Exploration of Immunology2768-66552023-08-013430032410.37349/ei.2023.00104Analytical dilemmas in lupus anticoagulant detectionGary W. Moore0https://orcid.org/0000-0002-2987-281XSpecialist Haemostasis Unit, Department of Haematology, Cambridge University Hospitals NHS Foundation Trust, CB2 0QQ Cambridge, UK; Department of Natural Sciences, Faculty of Science and Technology, Middlesex University, NW4 4BT London, UKAccurate lupus anticoagulant (LA) detection is crucial to antiphospholipid syndrome (APS) diagnosis. Detection is based on LA functional behavior in coagulation assays irrespective of epitope specificity. LA screening tests employ dilute phospholipids to accentuate in vitro inhibition by LAs, although they are not LA-specific and can be elevated by other coagulation abnormalities. Elevated screening tests are reflexed to mixing tests to distinguish between factor deficiency and inhibition. Confirmatory tests with high phospholipid concentration swamp LA to generate shorter clotting times than screening tests, whilst prolongation persists with non-phospholipid-dependent inhibitors. LA heterogeneity means that no single screening test detects every LA and the screen/mix/confirm medley must be applied to at least two assay types, usually dilute Russell’s viper venom time (dRVVT) and an LA-sensitive activated partial thromboplastin time (aPTT). Most laboratories restrict LA testing to these two assays, yet others, such as dilute prothrombin time (dPT), can perform with equal diagnostic efficacy, and additionally detect LA unreactive with dRVVT and aPTT. Converting clotting times to normalized ratios improves assay performance, and practitioners must choose between normal pooled plasma (NPP) clotting time denominators to reflect on-the-day assay performance, or reference interval (RI) mean clotting times to negate the effects of NPP variation. Cut-offs can be generated parametrically from normally distributed data, or different percentiles applied depending on the preferred balance between sensitivity and specificity. Sourcing sufficient donors for accurate cut-off estimations is problematic and transference exercises can be undertaken on low donor numbers. Analytical limitations of mixing tests have led to the adoption of alternative algorithms to the screen/mix/confirm test order, whilst some continue to rigidly apply the latter despite those limitations. Strategies to reduce or eliminate the effects of therapeutic anticoagulation have limitations, whilst the Taipan snake venom time (TSVT) screening test with an ecarin time (ET) confirmatory test is insensitive to vitamin K antagonist (VKA) and direct activated factor X anticoagulation.https://www.explorationpub.com/Journals/ei/Article/1003104activated partial thromboplastin timeantiphospholipid antibodiesconfirmatory testdilute prothrombin timedilute russell’s viper venom timemixing testscreening testtaipan snake venom time |
| spellingShingle | Gary W. Moore Analytical dilemmas in lupus anticoagulant detection Exploration of Immunology activated partial thromboplastin time antiphospholipid antibodies confirmatory test dilute prothrombin time dilute russell’s viper venom time mixing test screening test taipan snake venom time |
| title | Analytical dilemmas in lupus anticoagulant detection |
| title_full | Analytical dilemmas in lupus anticoagulant detection |
| title_fullStr | Analytical dilemmas in lupus anticoagulant detection |
| title_full_unstemmed | Analytical dilemmas in lupus anticoagulant detection |
| title_short | Analytical dilemmas in lupus anticoagulant detection |
| title_sort | analytical dilemmas in lupus anticoagulant detection |
| topic | activated partial thromboplastin time antiphospholipid antibodies confirmatory test dilute prothrombin time dilute russell’s viper venom time mixing test screening test taipan snake venom time |
| url | https://www.explorationpub.com/Journals/ei/Article/1003104 |
| work_keys_str_mv | AT garywmoore analyticaldilemmasinlupusanticoagulantdetection |