Alteration in the laboratory profile of a lupus anticoagulant in a patient with non-Hodgkin's lymphoma

Moore, Gary; Kamat, Anil Vaikunth; Gurney, David; O'Connor, O.; Rangarajan, Savita; Carr, Robert; Savidge, Geoffrey F.

doi:10.1111/j.1365-2257.2004.00644.x

Cited by 6 publications

(4 citation statements)

References 23 publications

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“…Additionally, spontaneous variation of APA has been reported to occur in up to 25% of cases [ 19 ] and TSVT/ET analysis could have a role in disease monitoring for patients on OAT whose antibody presentation or avidity changes over time [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Combining Taipan snake venom time/Ecarin time screening with the mixing studies of conventional assays increases detection rates of lupus anticoagulants in orally anticoagulated patients

Moore

2007

Thrombosis J

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Background: Oral anticoagulation compromises conventional lupus anticoagulant (LA) screening assays. Mixing studies can counteract the oral anticoagulant effect but the dilution reduces sensitivity and can generate false negative results. A firm diagnosis can be made from mixing studies when an elevated screen ratio is accompanied by a confirm ratio that generates significant correction to demonstrate phospholipid dependence, but also returns into the reference range, indicating complete normalisation of the oral anticoagulant effect. Taipan snake venom time (TSVT) with Ecarin time (ET) as a confirmatory test comprises an oral anticoagulant insensitive LA detection system and this study investigates the potential impact on detection rates when coupled with mixing studies on standard assays.

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Section: Discussionmentioning

confidence: 99%

Combining Taipan snake venom time/Ecarin time screening with the mixing studies of conventional assays increases detection rates of lupus anticoagulants in orally anticoagulated patients

Moore

2007

Thrombosis J

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“…Previous reports of high specificity for TSVT were corroborated with larger sample numbers, and some apparent false-positives could equally have been genuine LA that were unreactive with dRVVT or APTT, suggesting a potential role as second line testing in nonanticoagulated patients. 27,56,74 Anticoagulation with DOACs has become the standard of care for patients with a first unprovoked thrombosis yet results from clinical trials, however limited they may be, have led the European Medicines Agency to recommend avoiding DOAC anticoagulation in APS, particularly in triple-positive patients.…”

Section: The Oscutarin C Fraction Of Coastal Taipan (Oxyuranus Scutel...mentioning

confidence: 99%

International multicenter, multiplatform study to validate Taipan snake venom time as a lupus anticoagulant screening test with ecarin time as the confirmatory test: Communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies

Moore

Jones

Platton

et al. 2021

Journal of Thrombosis and Haemostasis

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Background Lupus anticoagulant (LA) assays are compromised in anticoagulated patients, and existing strategies to overcome the interferences have limitations. The prothrombin‐activating Taipan snake venom time (TSVT) screening test and ecarin time (ET) confirmatory test are innately insensitive to vitamin K antagonists (VKA) and direct factor Xa inhibitors (DFXaI). Objectives Validate standardized TSVT/ET reagents for LA detection, in a multicenter, multiplatform study. Patients/Methods Six centers from four countries analyzed samples with TSVT/ET from 81 nonanticoagulated patients with LA, patients with established antiphospholipid syndrome (APS), and proven persistent LA who were either not anticoagulated (n = 120) or were anticoagulated with VKAs (n = 180) or DFXaIs (n = 71). Additionally, 339 nonanticoagulated LA‐negative patients, and 575 anticoagulated non‐APS patients (172 VKA, 403 DFXaI) were tested. Anticoagulant spiking experiments were performed and 112 samples containing potential interferences (i.e., direct thrombin inhibitors) were tested. Results were evaluated against locally derived cutoffs. Imprecision was evaluated. Results Cutoffs were remarkably similar despite use of different analyzers and donor populations. Cutoffs for TSVT ratio, ET ratio, percent correction, and normalized TSVT ratio/ET ratio ranged between 1.08 and 1.10, 1.09 and 1.12, 9.3% and 14.8%, and 1.10 and 1.15, respectively. Coefficients of variation for TSVT and ET ratios were ≤5.0%. TSVT/ET exhibited sensitivity, specificity, and negative and positive predictive values of 78.2%/95.0%/86.3%/91.5%, respectively, with established APS as the LA‐positive population, and 86.9%/95.0%/76.8%/97.4%, respectively, with triple‐positive APS. Interference was seen with direct thrombin inhibitors, unfractionated heparin, and low molecular weight heparins, but not VKAs or DFXaIs. Conclusions TSVT/ET are validated for LA detection in nonanticoagulated patients and those on VKAs or DFXaIs.

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“…The absence of PL in the assay renders LA incapable of interfering, making it an ideal confirmatory test for FII-activating screening tests. TSVT was first described with a high PL concentration, platelet material-derived confirmatory test, until improved performance with ET as a confirmatory test was evidenced [66], and is now the most commonly used pairing of FII-activating LA assays [14,18]. ET can also be useful in instances where potent LAs partially or completely overcome the swamping effect of high PL concentration confirmatory reagents used for other assays [18,67].…”

Section: The Other La Assaysmentioning

confidence: 99%

Analytical dilemmas in lupus anticoagulant detection

Moore

2023

Explor Immunol

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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.

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Alteration in the laboratory profile of a lupus anticoagulant in a patient with non-Hodgkin's lymphoma

Cited by 6 publications

References 23 publications

Combining Taipan snake venom time/Ecarin time screening with the mixing studies of conventional assays increases detection rates of lupus anticoagulants in orally anticoagulated patients

Combining Taipan snake venom time/Ecarin time screening with the mixing studies of conventional assays increases detection rates of lupus anticoagulants in orally anticoagulated patients

International multicenter, multiplatform study to validate Taipan snake venom time as a lupus anticoagulant screening test with ecarin time as the confirmatory test: Communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies

Analytical dilemmas in lupus anticoagulant detection

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