Clinical and laboratory practice for lupus anticoagulant testing: An International Society of Thrombosis and Haemostasis Scientific and Standardization Committee survey

Abstract

Background Current guidelines have contributed to more uniformity in the performance and interpretation of lupus anticoagulant (LA) testing. However, points to reconsider include testing for LA in patients on anticoagulation, cut‐off values, and interpretation of results. Objectives The aim of this International Society of Thrombosis and Haemostasis Scientific and Standardization committee (ISTH SSC) questionnaire was to capture the spectrum of clinical and laboratory practice in LA detection, focusing on variability in practice, so that the responses could inform further ISTH SSC recommendations. Methods Members of the ISTH SSC on Lupus Anticoagulant/Antiphospholipid Antibodies and participants of the Lupus Anticoagulant/Antiphospholipid Antibodies Programme of the External quality Control of diagnostic Assays and Tests Foundation were invited to complete a questionnaire on LA testing that was placed on the ISTH website using RedCap, with data tallied using simple descriptive statistics. Results There was good agreement on several key recommendations in the ISTH and other guidelines on LA testing, such as sample processing, principles of testing, choice of tests, repeat testing to confirm persistent positivity and the use of interpretative reporting. However, the results highlight that there is less agreement on some other aspects, including the timing of testing in relation to thrombosis or pregnancy, testing in patients on anticoagulation, cut‐off values, and calculation and interpretation of results. Conclusions Although some of the variability in practice in LA testing reflects the lack of substantive data to underpin evidence‐based recommendations, a more uniform approach, based on further guidance, should reduce the inter‐center variability of LA testing.

Guidelines on the laboratory aspects of assays used in haemostasis and thrombosis

“…Screening for LA if often included as part of a thrombophilia screen programme. Guidance on performing LA testing is given elsewhere 104–107 …”

Lupus anticoagulant assay cut‐offs vary between reagents even when derived from a common set of normal donor plasmas

“…These discrepancies with the initial diagnostic testing could have arisen because the diagnostic testing was based on the finding of an elevated screening test before confirm and mixing tests were initiated. Every cut‐off represents a balance between sensitivity and specificity and some workers adopt higher cut‐offs (ie, 99th percentile versus 97.5th percentile) to reduce frequency of false‐positives . However, a non‐LA statistical outlier generating an elevated screening test will have a similar confirmatory test value that does not achieve mathematical confirmation of phospholipid dependence and a false‐positive interpretation will not ensue .…”

Escaping the catch 22 of lupus anticoagulant testing

“…Antiphospholipid syndrome (APS) is a clinical condition in patients with episodes of arterial thrombosis, venous thrombosis or pregnancy complications and presence of one or more of three types of antiphospholipid antibodies (aPL): lupus anticoagulant (LAC), anti-β2-glycoprotein 1 (β2-GP1) or anticardiolipin antibodies (aCL) demonstrated 12 weeks apart 1 2. LAC is an in vitro phenomenon observed when antibodies interfere with phospholipid-dependent laboratory analyses resulting in elongation of clotting times 1.…”

“…To rule out LAC, negative results with two methods are required 1. Most laboratories use dilute Russel’s Viper Venom Time (dRVVT) as first-line test and activated partial thromboplastin time (APTT) based analysis as second-line test 2. High titres of aPL and triple positivity for LAC, aCL and anti-β2GPI are associated with high thrombotic risk 3…”