Ruling out lupus anticoagulants with mixing test–specific cutoff assessment and the index of circulating anticoagulant
Abstract Background Lupus anticoagulant (LA) is classified in the antibody family that is recognized in antiphospholipid syndrome. Mixing tests are recommended for LA detection, and either a mixing test–specific cutoff (MTC) or index of circulating anticoagulant (ICA) is used for the interpretation....
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| Format: | Article |
| Language: | English |
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Elsevier
2019-10-01
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| Series: | Research and Practice in Thrombosis and Haemostasis |
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| Online Access: | https://doi.org/10.1002/rth2.12245 |
| _version_ | 1797715575457185792 |
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| author | Osamu Kumano Gary W. Moore |
| author_facet | Osamu Kumano Gary W. Moore |
| author_sort | Osamu Kumano |
| collection | DOAJ |
| description | Abstract Background Lupus anticoagulant (LA) is classified in the antibody family that is recognized in antiphospholipid syndrome. Mixing tests are recommended for LA detection, and either a mixing test–specific cutoff (MTC) or index of circulating anticoagulant (ICA) is used for the interpretation. Although we previously showed MTC had higher sensitivity for LA than ICA, there are few studies investigating specificity. Objectives To investigate specificity of multiple activated partial thromboplastin time (APTT) and diluted Russell's viper venom time (dRVVT) reagents for inhibitors using plasmas with non‐LA causes of prolonged clotting times, interpreted with MTC and ICA. Methods Seventy‐six factor‐deficient samples (either artificially prepared, hereditary deficiency, or warfarin), and 12 inhibitors (either coagulation factor inhibitors, rivaroxaban, or apixaban) were used. Samples were tested with 4 APTTs, 1 dilute APTT (dAPTT), and 2 dRVVT reagents, and all elevated screen ratios were followed up with mixing tests. Frequencies of corrected and not‐corrected results were calculated. Results The frequency of MTC and ICA corrected results, suggesting factor deficiency, were 5% to 43% and 79% to 100%, respectively, except for dAPTT, where MTC and ICA performed similarly. Frequencies of MTC and ICA not‐corrected results, suggesting inhibition, were 29% to 100% and 25% to 67%, respectively. Conclusions The data indicate that MTC has a tendency to generate not‐corrected mixing tests in factor‐deficient, warfarin, and other inhibitor samples, while ICA exhibited higher specificity. When we perform the mixing test and interpret the data, it is important to understand the characteristics of the indexes for maximizing the diagnostic potential of mixing test. |
| first_indexed | 2024-03-12T08:08:48Z |
| format | Article |
| id | doaj.art-60e640b4695244c89ff3888e2aa6d74c |
| institution | Directory Open Access Journal |
| issn | 2475-0379 |
| language | English |
| last_indexed | 2024-03-12T08:08:48Z |
| publishDate | 2019-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj.art-60e640b4695244c89ff3888e2aa6d74c2023-09-02T19:17:34ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792019-10-013469570310.1002/rth2.12245Ruling out lupus anticoagulants with mixing test–specific cutoff assessment and the index of circulating anticoagulantOsamu Kumano0Gary W. Moore1Protein Technology Sysmex Corporation Kobe Hyogo JapanDepartment of Haemostasis and Thrombosis Viapath Analytics Guy's & St. Thomas’ Hospitals London UKAbstract Background Lupus anticoagulant (LA) is classified in the antibody family that is recognized in antiphospholipid syndrome. Mixing tests are recommended for LA detection, and either a mixing test–specific cutoff (MTC) or index of circulating anticoagulant (ICA) is used for the interpretation. Although we previously showed MTC had higher sensitivity for LA than ICA, there are few studies investigating specificity. Objectives To investigate specificity of multiple activated partial thromboplastin time (APTT) and diluted Russell's viper venom time (dRVVT) reagents for inhibitors using plasmas with non‐LA causes of prolonged clotting times, interpreted with MTC and ICA. Methods Seventy‐six factor‐deficient samples (either artificially prepared, hereditary deficiency, or warfarin), and 12 inhibitors (either coagulation factor inhibitors, rivaroxaban, or apixaban) were used. Samples were tested with 4 APTTs, 1 dilute APTT (dAPTT), and 2 dRVVT reagents, and all elevated screen ratios were followed up with mixing tests. Frequencies of corrected and not‐corrected results were calculated. Results The frequency of MTC and ICA corrected results, suggesting factor deficiency, were 5% to 43% and 79% to 100%, respectively, except for dAPTT, where MTC and ICA performed similarly. Frequencies of MTC and ICA not‐corrected results, suggesting inhibition, were 29% to 100% and 25% to 67%, respectively. Conclusions The data indicate that MTC has a tendency to generate not‐corrected mixing tests in factor‐deficient, warfarin, and other inhibitor samples, while ICA exhibited higher specificity. When we perform the mixing test and interpret the data, it is important to understand the characteristics of the indexes for maximizing the diagnostic potential of mixing test.https://doi.org/10.1002/rth2.12245activated partial thromboplastin timeantiphospholipid antibodiesantiphospholipid syndromediluted Russell's viper venom timelupus anticoagulant |
| spellingShingle | Osamu Kumano Gary W. Moore Ruling out lupus anticoagulants with mixing test–specific cutoff assessment and the index of circulating anticoagulant Research and Practice in Thrombosis and Haemostasis activated partial thromboplastin time antiphospholipid antibodies antiphospholipid syndrome diluted Russell's viper venom time lupus anticoagulant |
| title | Ruling out lupus anticoagulants with mixing test–specific cutoff assessment and the index of circulating anticoagulant |
| title_full | Ruling out lupus anticoagulants with mixing test–specific cutoff assessment and the index of circulating anticoagulant |
| title_fullStr | Ruling out lupus anticoagulants with mixing test–specific cutoff assessment and the index of circulating anticoagulant |
| title_full_unstemmed | Ruling out lupus anticoagulants with mixing test–specific cutoff assessment and the index of circulating anticoagulant |
| title_short | Ruling out lupus anticoagulants with mixing test–specific cutoff assessment and the index of circulating anticoagulant |
| title_sort | ruling out lupus anticoagulants with mixing test specific cutoff assessment and the index of circulating anticoagulant |
| topic | activated partial thromboplastin time antiphospholipid antibodies antiphospholipid syndrome diluted Russell's viper venom time lupus anticoagulant |
| url | https://doi.org/10.1002/rth2.12245 |
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