Cited by 467Systemic Lupus Erythematosus ResearchBlood Coagulation and Thrombosis MechanismsHeparin-Induced Thrombocytopenia and Thrombosis

The DOI matches its Crossref record; 86 of the 88 references it cites were found in a registry or an index; 45 of the 85 sources its claims cite were checked for support.

Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis

Open access

Abstract

This guidance focuses on methodological aspects of lupus anticoagulant (LA) testing, as well as interpretation of results for clinicians. The main changes in how to test for LA compared with the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee 2009 guidelines, in the preanalytical phase are more detailed recommendations on how to handle testing in anticoagulated patients, and the timing of testing. Also, routine coagulation tests are advised to obtain more information on the coagulation background of the patient, and when necessary, anti-Xa activity measurement for heparins or specific assays for direct oral anticoagulants should be performed. The three-step procedure with two test systems (diluted Russell's viper venom time and activated partial thromboplastin time [aPTT]) is essentially not changed. Silica remains the preferable activator in the aPTT assays, but ellagic acid is not excluded. We advise simultaneous performance of the mixing and confirmatory step, in each sample with a prolonged screening test. The confirmatory step can also be performed on a mixture of patient plasma and normal pooled plasma. Cutoff values should be established in-house on at least 120 normals, with transference of the manufacturer's cutoffs as an alternative. Reporting of results has not been changed, although more attention is focused on what clinicians should know. Patient selection for LA testing has been expanded.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This ISTH-SSC guidance updates recommendations for lupus anticoagulant (LA) testing and interpretation, focusing on preanalytical factors, assay choice, cutoff values, result calculation, and timing. It retains the three-step screen-mix-confirm procedure with dRVVT and aPTT while adding detailed advice for anticoagulated patients, pregnancy, and persistent positivity.

Key findings

  • The three-step procedure with two test systems (dRVVT and aPTT) is essentially unchanged; silica remains the preferable aPTT activator, but ellagic acid is not excluded. The guidance advises simultaneous mixing and confirmatory steps in each sample with a prolonged screening test.
  • Cutoff values should be established in-house on at least 120 normals, with transference of manufacturer’s cutoffs as an alternative; the 99th centile is maintained. In the ISTH-SSC survey, 79% calculated in-house cutoffs but only 12% used >120 normals, and 50% applied the 99th centile.
  • Anticoagulant interference remains a major issue: DOACs give false-positive APTT and dRVVT results even at low concentrations; if DOACs are briefly interrupted, testing can be done at least 48 hours after the last dose, longer in renal impairment, with DOAC levels checked. For LMWH, samples should be taken at least 12 hours after the last dose and anti-Xa activity checked.
  • Repeat testing after an initial positive LA result is still recommended after at least 12 weeks to confirm persistent positivity; triple-positive patients may have predictable persistence, but the guidance concludes retesting after 12 weeks is still recommended.

Methods

  • This is consensus guidance from the ISTH-SSC for lupus anticoagulant/antiphospholipid antibodies, developed after a 2018 ISTH-SSC survey and panel discussion, with invited authors from the 2009 guidelines and other experts.
  • It reviews current literature and focuses on methodology, choice of assays, cutoff values, calculation and interpretation of results, and timing of testing in relation to thrombosis and pregnancy; laboratory aspects in anticoagulated patients are addressed in separate ISTH-SSC guidance.
  • Recommendations are presented in comparison with the ISTH-SSC 2009 guidelines, with a research agenda for unresolved issues.

Limitations

  • The paper states that some points need more evidence before being recommended and provides a research agenda, including optimal timing of initial and subsequent aPL testing, use of lower cutoffs in pregnancy, annual retesting, timing in stroke/TIA, multicenter validation of TSVT/ET, universal cutoff values, and biochemical basis of LA.
  • Evident from the text: this is expert consensus guidance rather than a systematic review or primary validation study, and several recommendations rely on survey practice and literature with acknowledged uncertainty or lack of agreement.
  • Evident from the text: cutoff values determined elsewhere cannot be transferred irrefutably between laboratories because of variables such as sample collection, tubes, normal population demographics, PNP variation, and reagent lots; interlaboratory variability remains a challenge.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1111/jth.15047

Cites

86 of 86 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

21 Partly supported · 14 No full text of the sources · 9 Supported · 4 Supported so far · 4 Own interpretation · 3 Sources not found · 2 Not checked yet · 2 Own result · 1 Couldn’t confirm · accuracy not yet measured

  • Probably not a substantial claim. 6
  • It may state two separate claims as one. 16
22 of 22
  • The paper relies on this without support.

    The survey respondents are representative of the spectrum of clinical and laboratory practice in LA detection.

    “The responses forced the formulation of further ISTH-SSC recommendations.”
  • The authors state this as an assumption.

    Manufacturers' cutoffs are established by appropriate statistical models using a sufficiently large donor population.

    “However, this assumes that manufacturers' cutoffs are established by appropriate statistical models using a sufficiently large donor population.”
2 of 2

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Citations

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Metadata

Authors
Devreese, K. M. J., de Groot, P. G., de Laat, B., Erkan, D., Favaloro, E. J., Mackie, I., Martinuzzo, M., Ortel, T. L., Pengo, V., Rand, J. H., Tripodi, A., Wahl, D., & Cohen, H.
Affiliations
  • Ghent University Hospital (BE)
  • Maastricht University Medical Centre (NL)
  • Hospital for Special Surgery (US)
  • Westmead Hospital (AU)
  • University College London (GB)
  • Hospital Italiano de Buenos Aires (AR)
  • Duke Medical Center (US)
  • University of Padua (IT)
  • Cornell University (US)
  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
  • Inserm (FR)
  • University College Hospital (GB)
Corresponding author
Devreese, Katrien M.J.
Venue
Journal of Thrombosis and Haemostasis
Publisher
Elsevier BV
Published
2020-11
Volume
18
Issue
11
Pages
2828-2839
ISSN
1538-7836 (ISSN-L)
OpenAlex
W3096784218
Cited by
467
References
88
Citations by year
2026: 85 · 2025: 80 · 2024: 103 · 2023: 94 · 2022: 57 · 2021: 43 · 2020: 4
FWCI
31.46
Type
journal article
Language
en
Open access
Locations
  • Journal of Thrombosis and Haemostasis (publishedVersion)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (publishedVersion, other-oa)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion)
  • Research Publications (Maastricht University) (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
  • Health Sciences › Medicine › Hematology › Heparin-Induced Thrombocytopenia and Thrombosis
Keywords
lupus anticoagulant, antiphospholipid antibodies, pre-analytical phase, anticoagulated patients, coagulation tests, anti-Xa activity, direct oral anticoagulants, activated partial thromboplastin time, ellagic acid, cut-off values, patient selection, thrombosis
MeSH terms
Blood Coagulation Tests, Humans, Partial Thromboplastin Time, Prothrombin Time, Reference Standards, Thrombosis, Lupus Coagulation Inhibitor, Antiphospholipid Syndrome

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