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, Gary W. ORCID: https://orcid.org/0000-0002-2987-281X, Jones, Paul O., Platton, Sean ORCID: https://orcid.org/0000-0002-5466-0448, Hussain, Nadia, White, Danielle, Thomas, Will ORCID: https://orcid.org/0000-0001-8740-0194, Rigano, Joseph, Pouplard, Claire, Gray, Elaine and Devreese, Katrien M. J. ORCID: https://orcid.org/0000-0002-7559-2579 (2021) 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. Journal of Thrombosis and Haemostasis, 19 (12) . pp. 3177-3192. ISSN 1538-7933 [Article] (doi:10.1111/jth.15438)

Preview

PDF - Final accepted version (with author's formatting) Download (17MB) | Preview

Abstract

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.

Actions (login required)

View Item

Statistics

DownloadsShow export options

Export as CSVXMLJSON

Activity Overview

6 month trend

14Downloads

6 month trend

90Hits

Additional statistics are available via IRStats2.