Cited by 149Systemic Lupus Erythematosus ResearchBlood Coagulation and Thrombosis MechanismsHeparin-Induced Thrombocytopenia and Thrombosis

The DOI matches its Crossref record; 78 of the 78 references it cites were found in a registry or an index; none of the 134 sources its claims cite is checked for support yet.

Recent Guidelines and Recommendations for Laboratory Detection of Lupus Anticoagulants

Open access
Moore, Gary·2014·Seminars in Thrombosis and Hemostasis

Abstract

The International Society on Haemostasis and Thrombosis (ISTH) and the British Committee for Standards in Haematology (BCSH) have recently updated their lupus anticoagulant (LA) detection guidelines. The Clinical and Laboratory Standards Institute (CLSI) subsequently will publish its first LA guideline. General agreement exists on issues such as sample preparation, the use of dilute Russell viper venom time (dRVVT) in diagnostic repertoires, the use of normalized ratios, calculations to demonstrate phospholipid dependence, calculations to demonstrate inhibition, and interpretive reporting. The ISTH recommendation to employ only dRVVT and activated partial thromboplastin time is not mirrored in the BCSH and CLSI documents. The potential for false negatives in mixing tests is acknowledged by all panels, yet they remain mandated by ISTH as there are occasions when they are crucial to diagnostic accuracy. BCSH indicates that a negative mixing test need not exclude the presence of a LA, and CLSI reprioritizes test order to screen-confirm-mix, the latter being considered unnecessary in specific circumstances. Opinions in the guidelines differ on setting cutoff levels (i.e., 97.5th vs. 99th percentile for normally distributed data). All guidelines cover testing of anticoagulated patients, more detail being given by BCSH and CLSI, who suggest that Taipan snake venom time is a useful adjunct test in patients receiving vitamin K antagonists. Although complete agreement is not apparent, the guidelines represent significant moves toward engendering common practices.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This review compares recent ISTH 2009, BCSH 2012, and CLSI 2014 guidelines for laboratory detection of lupus anticoagulants, highlighting commonalities and contrasts across preanalytical, assay, interpretive, and anticoagulated-patient issues. Although agreement exists on many practices, the guidelines differ on screening assay repertoire, cutoff percentiles, mixing-test placement, ratio denominators, and testing on anticoagulated patients.

Key findings

  • All three guidelines agree on double centrifugation to platelet-poor plasma (<10 × 10⁹/L), inclusion of dRVVT in diagnostic repertoires, use of normalized ratios, calculations for phospholipid dependence and inhibition, interpretive reporting, and retesting in no less than 12 weeks; ISTH 2009 uniquely restricts screening to dRVVT plus aPTT, whereas BCSH 2012 and CLSI 2014 permit other assays.
  • Cutoff/reference-interval differences are prominent: ISTH 2009 recommends the 99th percentile (mean + 2.3 SD for normally distributed data) but this is controversial because it states a minimum of 40 donors, whereas 120 has previously been recommended; BCSH 2012 and CLSI 2014 favor the 97.5th percentile if Gaussian, with BCSH suggesting validation of established cutoffs using 20 to 60 normal donors. CLSI 2014 normalizes against the RI mean, not the NPP value.
  • Mixing-test strategy differs: ISTH 2009 uses screen-mix-confirm; BCSH 2012 uses screen-mix-confirm but states a negative mixing test need not exclude LA; CLSI 2014 reprioritizes to screen-confirm-mix, omitting mixing when initial testing is clear cut. All agree mixing tests use a 1:1 mixture of test plasma and NPP, and ISTH/CLSI support interpretation by ICA or a mixing-test-specific cutoff.
  • For anticoagulated patients, all agree testing on VKA or therapeutic UFH should be postponed if possible; ISTH 2009 permits undiluted plasma if INR <1.5 and 1:1 NPP mixing if INR 1.5–3.0, while BCSH 2012 and CLSI 2014 use 1:1 NPP mixes without that INR restriction and suggest TSVT with ET or PNP for VKA patients. CLSI 2014 details newer anticoagulant interference: DTIs interfere with all LA assays, rivaroxaban affects dRVVT more than aPTT, and TSVT/ET may detect LA in patients on rivaroxaban.

Methods

  • Narrative review comparing three guidelines: ISTH 2009, BCSH 2012, and CLSI 2014, with reference to prior literature and a summary table.
  • No primary patient cohort or systematic search is described; the evidence base is the published guidelines and cited studies.
  • Main analysis is thematic: preanalytical variables, reference intervals/cutoffs, screening tests, mixing tests, ratios, confirmatory tests, integrated testing, anticoagulated patients, and reporting.

Limitations

  • The paper states that LA detection lacks gold standards and is challenged by antibody heterogeneity, reagent and analyzer variability, differing interpretation strategies, and incomplete agreement among contemporaneous guidelines; consensus guidelines rely heavily on expert opinion and are prone to bias.
  • The paper notes that some recommendations are controversial or expert-opinion-based, such as the ISTH 99th-percentile donor minimum and mixing-test mandates, and that no guideline fully agrees with the others.
  • Evident from the text: this is a narrative review without systematic review or meta-analysis or primary data, so conclusions reflect the author’s interpretation of selected guidelines and literature.

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

Integrity signals

Registry

Crossref · 10.1055/s-0033-1364185

Cites

78 of 78 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

70 Sources not found · 23 Own interpretation · 17 No basis given

Show all 36 claims

  • Probably not a substantial claim. 45
  • It may state two separate claims as one. 47
74 of 74
  • The paper relies on this without support.

    No gold standard method for LA detection exists.

    “Problems such as antibody heterogeneity, reagent and analyzer variability, differing interpretation strategies, and absence of gold standards continue to conspire against generation of unequivocally ideal diagnostic strategies.”
    “CLSI 2014 deliberately avoids the use of “LAsensitive/LA-insensitive” terminology, based on the concept that “LA sensitivity” is difficult to appropriately define due to the lack of any “gold standard” LA detection method.”
  • The paper relies on this without support.

    Diagnostic laboratories are often asked to test for LAs in anticoagulated patients, often without knowing a patient is receiving them until laboratory results suggest so.

    “However, the reality for diagnostic laboratories is that they are often asked to test for LAs in anticoagulated patients, often without knowing a patient is receiving them until laboratory results suggest so, and guidance is required.”
2 of 2

Claims other papers make about this one

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Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

1 of 1

Citations

Cites

Show all 77 references

Research works printed but not linked: 2

  1. CLSI. Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline-Third Edition. CLSI document EP28-A3c. Wayne, PA: Clinical and Laboratory Stand- ards Institute; 2008
  2. Moore GW. Clinical utility of the less commonly employed assays for lupus anticoagulation detection: the evidence. J Coag Dis 2010; 2:69-79

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Metadata

Authors
Moore, G.
Affiliations
St Thomas' Hospital (GB)
Corresponding author
Moore, Gary
Venue
Seminars in Thrombosis and Hemostasis
Published
2014-02-05
Volume
40
Issue
02
Pages
163-171
ISSN
  • 0094-6176 (ISSN-L)
  • 1098-9064
OpenAlex
W2084030336
Cited by
149
References
77
Citations by year
2026: 2 · 2025: 3 · 2024: 6 · 2023: 7 · 2022: 14 · 2021: 13 · 2020: 12 · 2019: 23 · 2018: 13 · 2017: 20 · 2016: 16 · 2015: 13 · 2014: 7
FWCI
12.98
Type
journal article
Language
en
Open access
Locations
  • Seminars in Thrombosis and Hemostasis (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
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, dilute Russell viper venom time, activated partial thromboplastin time, mixing test, phospholipid dependence, cut-off values, anticoagulated patients, vitamin K antagonists, CLSI
MeSH terms
Anticoagulants, Blood Coagulation Tests, Humans, Reagent Kits, Diagnostic, Sensitivity and Specificity, Reproducibility of Results, Lupus Coagulation Inhibitor, Antiphospholipid Syndrome, Guidelines as Topic, Clinical Laboratory Techniques

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