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

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 standardised TSVT/ET reagents for LA detection, in a multi-centre, multi-platform study.
Patients/Methods
Six centres from four countries analysed samples with TSVT/ET from 81 non-anticoagulated 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 non-anticoagulated 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 cut-offs. Imprecision was evaluated.
Results
Cut-offs were remarkably similar despite use of different analysers and donor populations. Cut-offs for TSVT ratio, ET ratio, percent correction and normalised TSVT ratio/ET ratio ranged between 1.08-1.10, 1.09-1.12, 9.3%-14.8% and 1.10-1.15 respectively. Coefficients of variation for TSVT and ET ratios were ≤5.0%. TSVT/ET exhibited sensitivity, specificity, 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 non-anticoagulated patients and those on VKAs or DFXaIs.

This is the peer reviewed version of the following article: Moore, GW, Jones, PO, Platton, S, et al. 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. J Thromb Haemost. 2021; 19: 3177– 3192, which has been published in final form at https://doi.org/10.1111/jth.15438. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited