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Cited by 148Systemic Lupus Erythematosus ResearchBlood Coagulation and Thrombosis MechanismsHeparin-Induced Thrombocytopenia and Thrombosis

Recent Guidelines and Recommendations for Laboratory Detection of Lupus Anticoagulants

Open access
Moore, Gary·2014·Seminars in Thrombosis and Hemostasis
DOI 10.1055/s-0033-1364185
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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.

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

77 of 77 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 134 cited sources checked · 0 supported · 0 flagged

  • Findingnone given

    All three guideline panels acknowledge the potential for false negatives in mixing tests.

    “The potential for false negatives in mixing tests is acknowledged by all panels,”
    Quote in the paperNot a substantial claim
  • Findingreasoning

    There is full consensus that blood for LA testing, collected into 0.109 mol/L trisodium citrate, must be rendered platelet poor by double centrifugation to achieve a final platelet count of <10×10^9/L.

    “There is full consensus that blood for LA testing, collected into 0.109 mol/L trisodium citrate, must be rendered platelet poor by a process of double centrifugation, to achieve a final platelet count of < 10 Â 10 9 /L.”
    Quote in the paperSubstantial claim
  • Findingreasoning

    Performing 10 screening tests, with only one needing to be positive, could theoretically identify 12.5% of tested normal individuals as positive using a 97.5th percentile cutoff.

    “As a statistical example, performance of 10 screening tests, with only one needing to be positive for potentially defining positivity for the condition, could theoretically identify 12.5% of tested (normal) individuals as being positive for the condition using a 97.5th percentile cutoff.”
    Quote in the paperNot a substantial claim
  • Findingreasoning

    All three guidelines agree that confirmatory tests used to demonstrate phospholipid dependence must be based on the screening test(s) that was abnormal.

    “All three guidelines agree that confirmatory tests used to demonstrate phospholipid dependence must be based on the screening test(s) that was abnormal.”
    Quote in the paperSubstantial claim
  • Premisecitation

    A single centrifugation step may be inefficient for achieving the target platelet count of <10×10^9/L in all samples.

    “Thus, a single centrifugation step may be inefficient for achieving the target of < 10 Â 10 9 /L in all samples.6”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [6]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim. 45
  • May combine two claims. 47

  • Classified as probably not a substantial claim.

    Findingnone given

    The ISTH recommendation to employ only dRVVT and activated partial thromboplastin time is not mirrored in the BCSH and CLSI documents.

    “The ISTH recommendation to employ only dRVVT and activated partial thromboplastin time is not mirrored in the BCSH and CLSI documents.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    The guidelines differ in opinion on setting cutoff levels (97.5th vs. 99th percentile for normally distributed data).

    “Opinions in the guidelines differ on setting cutoff levels (i.e., 97.5th vs. 99th percentile for normally distributed data).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    General agreement exists among the ISTH, BCSH and CLSI LA guidelines on sample preparation, the use of dRVVT in diagnostic repertoires, the use of normalized ratios, calculations to demonstrate phospholipid dependence, calculations to demonstrate inhibition, and interpretive reporting.

    “General agreement exists on issues such as sample preparation, the use of dilute Russell viper venom time (dRVVT) in diagnostic repertoires,”
    • Also stated in: § Abstract · plain
      “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.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Findingnone given

    CLSI reprioritizes test order to screen-confirm-mix, the mixing test being considered unnecessary in specific circumstances.

    “CLSI reprioritizes test order to screen-confirm-mix, the latter being considered unnecessary in specific circumstances.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    BCSH indicates that a negative mixing test need not exclude the presence of a LA.

    “BCSH indicates that a negative mixing test need not exclude the presence of a LA,”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingnone given

    The guidelines differ on the recommended centrifugation technique, with ISTH 2009 recommending differential speeds on first and second spins.

    “The guidelines also differ on the recommended centrifugation technique, with ISTH 2009 recommending differential speeds on first and second spins.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingnone given

    All guidelines cover testing of anticoagulated patients, with more detail given by BCSH and CLSI, who suggest that Taipan snake venom time is a useful adjunct test in patients receiving vitamin K antagonists.

    “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.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    BCSH 2012 and CLSI 2014 discourage ultracentrifugation (>5,000g) in the second step because it may generate microparticles.

    “BCSH 2012 and CLSI 2014 discourage ultracentrifugation (> 5,000g) in the second step because it may generate microparticles.5,7”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [5]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [7]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Findingnone given

    ISTH 2009 is the only document to specify dilute phospholipid, whereas the phrasing in the other two guidelines can encompass routine aPTT reagents without dilute phospholipid but recognized to be relatively LA-responsive.

    “ISTH 2009 is the only document to specify dilute phospholipid, whereas phrasing in the other two guidelines can encompass routine aPTT reagents without dilute phospholipid but recognized to be (relatively) LAR.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingreasoning

    There is a clear continuum of views across the three guidelines concerning mixing tests.

    “There is a clear continuum of views across the three guidelines concerning mixing tests.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    Neither BCSH 2012 nor CLSI 2014 restricts aPTT reagents based on activator alone.

    “Consequently, neither BCSH 2012 nor CLSI 2014 restricts aPTT reagents based on activator alone.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    Asymptomatic patients positive for all three of LA, anticardiolipin antibodies, and anti-β2 glycoprotein I antibodies are at high risk of incurring a thromboembolic event.

    “a recent study revealed that asymptomatic patients positive for all three of LA, anticardiolipin antibodies, and anti-β 2 glycoprotein I antibodies are at high risk of incurring a thromboembolic event, 12”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [12]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S4 (based).

    Findingnone given

    No guideline before ISTH 2009 gave definitive advice for interpreting mixing tests.

    “No guideline before ISTH 2009 gave definitive advice for interpreting mixing tests, so it was especially welcome that this publication fully addresses the issue.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingnone given

    BCSH has championed the percentage correction of ratio calculation since 1991, with a correction of 10% or more being indicative of the presence of a LA, whereas ISTH 2009 indicates that the cutoff should be locally derived.

    “BCSH has championed this calculation since 1991, with a correction of 10% or more being indicative of the presence of a LA, whereas ISTH 2009 indicates that the cutoff should be locally derived.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    All guidelines agree that mixing tests should be performed on a 1:1 mixture of test plasma and normal pooled plasma.

    “All guidelines agree that mixing tests should be performed on a 1:1 mixture of test plasma and NPP.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationnone given

    Antibody heterogeneity, reagent and analyzer variability, differing interpretation strategies, and absence of gold standards continue to prevent the generation of unequivocally ideal diagnostic strategies for LA.

    “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.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: No gold standard method for LA detection exists.

  • Classified as probably not a substantial claim.

    Interpretationnone given

    Lupus anticoagulants are detected by inference, after exclusion of other possible causes of test findings.

    “Lupus anticoagulants (LA) are somewhat akin to subatomic particles and extrasolar planets, in that they are “detected” by inference, after exclusion of other possible causes of test findings.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationreasoning

    Although complete agreement is not apparent, the guidelines represent significant moves toward engendering common practices.

    “Although complete agreement is not apparent, the guidelines represent significant moves toward engendering common practices.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    ISTH mandates mixing tests because there are occasions when they are crucial to diagnostic accuracy.

    “yet they remain mandated by ISTH as there are occasions when they are crucial to diagnostic accuracy.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Filtration through 0.22 μm cellulose acetate filters is no longer recommended because it introduces variables such as loss of von Willebrand factor and some other coagulation factors.

    “The previously fashionable filtration through 0.22 μm cellulose acetate filters is no longer recommended because it introduces variables such as loss of von Willebrand factor and some other coagulation factors.8”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [8]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    The BCSH 2012 recommendation to employ a LAR-aPTT or modified aPTT can reasonably be taken to include use of KCT, SCT, or dilute aPTT.

    “The BCSH 2012 recommendation to employ a LAR-aPTT or modified aPTT can reasonably be taken to include use of KCT, SCT, or dilute aPTT.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    No single assay system will detect all LAs, and therefore multiple assays using differing analytical principles are required to achieve acceptable detection rates.

    “It has long been recognized that no single assay system will detect all LAs and therefore multiple assays, using differing analytical principles, are required to achieve acceptable detection rates.19,20”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [19]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [20]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationreasoning

    Non-LA causes of elevated screening tests would not normally lead to false-positive composite interpretation; the issue becomes performing unnecessary confirmatory tests.

    “These non-LA examples, however, would not normally lead to false-positive composite interpretation, for the reasons described above, and the issue becomes more that of performing unnecessary confirmatory tests.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Data from normal donor populations for clotting tests are commonly Gaussian or near Gaussian, or can be made so by data transformation, though this requires confirmation with each assessment to be suitable for parametric statistics.

    “data from normal donor populations for clotting tests are commonly Gaussian or near Gaussian, or can be made so by data transformation, 14,16 although this requires confirmation with each assessment to enable data to be suitable for parametric statistics.17”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [14]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [16]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [17]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Inconsistent sensitivity of aPTT reagents to LA is largely due to variation in phospholipid concentration or composition, and ellagic acid-containing reagents can be suitable for LA detection.

    “inconsistent sensitivity of aPTT reagents to LA is largely due to variation in phospholipid concentration or composition and ellagic acid-containing reagents can be suitable for LA detection.17,25,31”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [17]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [25]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [31]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    dRVVT has repeatedly been shown to be sensitive to β2 glycoprotein I-dependent antibodies and highly correlated with thrombosis.

    “this test procedure has repeatedly been shown to be sensitive to β 2 glycoprotein Idependent antibodies and highly correlate with thrombosis.22”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [22]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    An important limitation of the KCT is that it lacks a widely available confirmatory test, thereby compromising specificity by not fulfilling an indispensable diagnostic criterion.

    “an important limitation for the KCT is that it lacks a widely available confirmatory test, thereby compromising specificity by not fulfilling an indispensable diagnostic criterion.28”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [28]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The kaolin clotting time is often quoted as being one of the most sensitive assays for LA because of its extremely low phospholipid concentration.

    “The kaolin clotting time (KCT) is often quoted as being one of the most sensitive assays for LA because of its extremely low phospholipid concentration.5”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Interpretationnone given

    Preliminary routine coagulation screening, including prothrombin time, aPTT and thrombin time, is crucial before LA testing to exclude undiagnosed coagulopathies or undisclosed anticoagulant therapy.

    “Preliminary routine coagulation screening, including prothrombin time, activated partial thromboplastin time (aPTT), and thrombin time, are crucial before LA testing to exclude undiagnosed coagulopathies or undisclosed anticoagulant therapy.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    A 99th percentile value cannot be derived from a minimum of 40 donors; a minimum of 120 donors has been previously recommended.

    “the guideline states that a 99th percentile value can be derived from a minimum of 40 donors, yet this is not the case and a minimum of 120 has been previously recommended.18”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationreasoning

    An elevated LA screening test in isolation is not a false-positive result but merely a prolonged clotting time requiring confirmatory tests to reveal whether the initial abnormality is due to a LA.

    “An important point is made that an elevated LA screening test in isolation is not a false-positive result but merely a prolonged clotting time requiring confirmatory tests to reveal whether or not the initial abnormality is due to a LA.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Technical difficulties with the KCT (meticulous sample handling, long clotting times, variation in residual lipid) mean that its reproducibility is poor relative to other tests, which is why ISTH 2009 does not recommend it.

    “Technical difficulties such as meticulous sample handling, long clotting times, and variation in residual lipid mean that reproducibility is poor relative to other tests and these issues provide the reasons that ISTH 2009 does not recommend this assay.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Statistical outliers or other causes of prolonged clotting times will usually generate an equally elevated confirmatory test result for that assay and not generate a false-positive interpretation.

    “Statistical outliers or other causes of prolonged clotting times will usually generate an equally elevated confirmatory test result for that assay, and crucially, not generate a false-positive interpretation.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationreasoning

    It is impractical and probably unnecessary for all laboratories to adopt extensive LA-assay repertoires, but there is a case for the use of additional assays in select patients or circumstances.

    “It is impractical and probably unnecessary for all laboratories to adopt extensive LA-assay repertoires, but there is a case for the use of additional assays in select patients or circumstances.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Although most commercial dRVVT reagents behave similarly, occasional deviations in behavior occur.

    “although most commercial dRVVT reagents behave similarly, potentially suggesting common manufacturing practices, occasional deviations in behavior occur.23”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Diluting a phospholipid preparation of LA-unresponsive composition may not perform as well as an undiluted LAR preparation, yet the latter risks missing weaker antibodies if the phospholipid is too concentrated.

    “Diluting a phospholipid preparation of LA-unresponsive composition may not perform as well as an undiluted LAR preparation, 19,24 yet the latter risks missing weaker antibodies if the phospholipid is too concentrated.22,25”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [19]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [24]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [22]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationreasoning

    New or alternative LA assays are commonly evaluated against dRVVT and/or aPTT and are thus disadvantaged because they may be sensitive to different antibody subpopulations; comparison against the dRVVT/aPTT combination ostensibly creates a selection bias.

    “New or alternative assays are commonly evaluated against dRVVT and/or aPTT, and are thus disadvantaged because they may be sensitive to different antibody subpopulations.Comparison against the dRVVT/aPTT combination ostensibly creates a selection bias.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Assays other than dRVVT and aPTT can detect clinically significant antibodies undetectable in dRVVT and aPTT as well as many that are detectable.

    “these assays can detect clinically significant antibodies undetectable in dRVVT and aPTT as well as many that are.28”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [28]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationreasoning

    A false-positive screening test obtained from the use of the 97.5th percentile will not generate false-positive composite interpretation, whereas a false-negative resulting from application of the 99th percentile could lead to failure to secure appropriate diagnosis and treatment.

    “A false-positive screening test obtained from the use of the 97.5th percentile will not generate false-positive composite interpretation, yet a false-negative resulting from application of the 99th percentile could lead to failure to secure appropriate diagnosis and treatment.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Some patients will generate an elevated screening test with at least one test/reagent type, and the chance of this increases the more tests are performed.

    “it is likely that some patients will generate an elevated screening test with at least one test/reagent type, with the chance on this increasing the more tests performed.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The relatively recent availability of a standardized commercially available dPT reagent kit has led to the suggestion that LA detection is improved when dRVVT and aPTT are accompanied by dPT.

    “The relatively recent availability of a standardized commercially available reagent kit has led to the suggestion that LA detection is improved when dRVVT and aPTT are accompanied by dPT.34,37”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [34]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [37]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationreasoning

    Applying the 99th percentile cutoff reduces the frequency of false-positive results and increases specificity, but reduces sensitivity.

    “This introduces potential to reduce the frequency of false-positive results and thereby increase specificity, yet it is a statistical inevitability that this will reduce sensitivity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Less commonly employed assays can detect LA that will not manifest in dRVVT and aPTT, and at least some of these antibodies are clinically significant.

    “The less commonly employed assays can detect LA that will not manifest in dRVVT and aPTT, and at least some of these antibodies are clinically significant.28,[32][33][34][35][40][41][42][43]”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [28]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [32]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [33]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Premisecitation

    The CLSI 2014 recommendations affirm that the decision to omit mixing tests can only be made on a case-by-case basis.

    “The CLSI 2014 recommendations for when mixing tests can be omitted or not, crystallize this debate, and they affirm that the decision can only be made on a case-by-case basis.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites CLSI 2014

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    The confirmatory test on undiluted plasma must not only mathematically correct an elevated screening test result but should also return into the reference interval.

    “the confirmatory test (on undiluted plasma) must not only mathematically correct an elevated screening test result but should also return into the RI.51”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [51]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Premisecitation

    ISTH 2009 states that performing screen and confirm tests in parallel on undiluted plasma does not, in principle, require subsequent performance of a mixing test.

    “A statement in ISTH 2009 that performing screen and confirm tests in parallel on undiluted plasma does not, in principle, require subsequent performance of a mixing test and has prompted useful and revealing debate.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites ISTH 2009

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationreasoning

    Using a mixing test-specific reference interval, which is narrower than that for undiluted plasma and thus has a lower cutoff, increases sensitivity compared with assessing against the cutoff for undiluted plasma.

    “The lower cutoff increases sensitivity in comparison to assessing against the cutoff for undiluted plasma.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Establishing the reference interval and its mean by analyzing normal donors over several days accounts for innate technique variability, and running an NPP as a normal control will identify sudden analytical difficulties.

    “Establishing the RI and its mean by analyzing normal donors over several days accounts for innate technique variability, 18 and running an NPP as a normal control will identify sudden analytical difficulties.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationcitation

    The LA cofactor effect cannot, by definition, be demonstrated without mixing tests, and integrated testing alone will not detect this phenomenon.

    “Although considered rare, the LA cofactor effect cannot, by definition, be demonstrated without mixing tests, and integrated testing alone will not detect this phenomenon.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [62]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [66]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Premisecitation

    In the absence of other causes of prolonged clotting times, samples with negative mixing tests but clear positive screen and confirm tests on undiluted plasma can be considered LA positive.

    “in the absence of other causes of prolonged clotting times, samples with negative mixing tests but clear positive screen and confirm tests on undiluted plasma can be considered LA positive.[44][45][46]”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [44]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [45]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [46]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationcitation

    Some laboratories apply only the mixing test in response to an elevated aPTT and are at risk of both loss of specificity and increased false-negative interpretations unless dRVVT testing is also positive.

    “some laboratories apply only the mixing test in response to an elevated aPTT and are at risk of both loss of specificity and increased false-negative interpretations unless dRVVT testing is also positive.[44][45][46][47][48][49]57,58”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [44]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [45]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [46]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    CLSI 2014 reserves its definition of integrated tests for those that incorporate dilution in NPP, while ISTH 2009 includes those performed on undiluted test plasma and a separate mixing test.

    “CLSI 2014 reserves its definition of integrated tests for those that incorporate dilution in NPP, while ISTH 2009 includes those performed on undiluted test plasma and a separate mixing test.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites CLSI 2014

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites ISTH 2009

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Not all NPPs, or batches of the same NPP, generate the same clotting times with different reagents for the same test type, so false-positive and false-negative results can ensue if an NPP value is toward or beyond an extreme of a reference interval.

    “not all NPPs, or batches of the same NPP, generate the same clotting times with different reagents for the same test type, 13,14,55,57 so that false-positive and false-negative results can ensue if an NPP value is toward or beyond an extreme of a RI.55”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [13]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [14]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [55]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    No mathematical method for assessing mixing test data can perfectly discriminate between factor deficiencies and inhibitors, and cutoffs vary between test types and reagents.

    “no mathematical method for assessing mixing test data can perfectly discriminate between factor deficiencies and inhibitors, and cutoffs vary between test types and reagents.53,54”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [53]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [54]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    BCSH 2012 indicates that brief discontinuation of VKA therapy is not a high-risk strategy in most cases where decisions on advisability of long-term anticoagulation are required.

    “BCSH 2012 indicates that brief discontinuation of VKA therapy is not a high-risk strategy in most cases, where decisions on advisability of long-term anticoagulation are required.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites BCSH 2012

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    Integrated testing circumvents the traditional testing order of screen-mix-confirm, and the presence of a LA can be immediately apparent without performing the mixing test.

    “The principle arises from the fact that the traditional testing order of screen-mix-confirm is circumvented and the presence of a LA can be immediately apparent without performing the mixing test.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    All three guidelines state that the numerical results should be accompanied by an interpretation indicating whether the findings are consistent with the presence or absence of an LA (or the inability to detect an LA).

    “All three guidelines state that the numerical results should be accompanied by an interpretation indicating whether the findings are consistent with the presence or absence of an LA (or more correctly the inability to detect an LA).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites ISTH 2009

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites BCSH 2012

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites CLSI 2014

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    If the INR is between 1.5 and 3.0, ISTH 2009 indicates that undertaking the tests on 1:1 mixtures with NPP can be considered, with recognition of the dilution effect.

    “If the INR is between 1.5 and 3.0, undertaking the tests on 1:1 mixtures with NPP can be considered, with recognition of the dilution effect.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites ISTH 2009

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Mixing tests can be omitted in certain circumstances in the LA analytical hierarchy.

    “There is more debate to be had about the place of mixing tests in the LA analytical hierarchy, although it does seem that they can be omitted in certain circumstances.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    ISTH 2009 indicates that dRVVT and aPTT can be performed on undiluted plasma if the INR is less than 1.5.

    “ISTH 2009 indicates that dRVVT and aPTT can be performed on undiluted plasma if the international normalized ratio (INR) is less than 1.5.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites ISTH 2009

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    BCSH 2012 states that an elevated screen on the mixture can be taken as grounds to suspect an inhibitor and the confirm will demonstrate phospholipid dependence.

    “BCSH 2012 states that an elevated screen on the mixture can be taken as grounds to suspect an inhibitor and the confirm will demonstrate phospholipid dependence.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites BCSH 2012

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Premisecitation

    BCSH 2012 and CLSI 2014 consider that there is sufficient evidence for other tests that they should not be discounted in their entirety.

    “BCSH 2012 and CLSI 2014 consider that there is sufficient evidence for other tests that they should not be discounted in their entirety.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites BCSH 2012

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites CLSI 2014

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    BCSH 2012 and CLSI 2014 advocate performing screen and confirm tests on 1:1 mixtures with NPP but do not restrict this practice to plasmas with INRs 3.0.

    “BCSH 2012 and CLSI 2014 advocate performing screen and confirm tests on 1:1 mixtures with NPP but do not restrict this practice to plasmas with INRs 3.0.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites BCSH 2012

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites CLSI 2014

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Direct thrombin inhibitors (DTI), such as dabigatran and argatroban, interfere with all LA assays and introduce a significant risk of false-positive results.

    “Direct thrombin inhibitors (DTI), such as dabigatran and argatroban, interfere with all LA assays and introduce a significant risk of falsepositive results.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [17]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [74]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Testing undiluted plasma can lead to false-positive or false-negative results, and is thus not recommended.

    “Testing undiluted plasma can lead to false-positive or false-negative results, and is thus not recommended, 13,17,20,69 although some workers contend that it can be reliable.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [13]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [17]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [20]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [69]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Premisecitation

    Each of the three guidelines supports the recommendation to retest in no less than 12 weeks when a LA is initially detected.

    “Each document supports the recommendation to retest in no less than 12 weeks when a LA is initially detected.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites ISTH 2009

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites BCSH 2012

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites CLSI 2014

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    CLSI 2014 indicates that reagent-integral heparin neutralizers quench heparin only up to a specified level, and it must be demonstrated that this has occurred before result interpretation is undertaken.

    “CLSI 2014 discusses reagent-integral heparin neutralizers (as found in most commercial dRVVT reagents) in more detail, indicating that they quench heparin only up to a specified level, and it must be demonstrated that this has occurred before result interpretation is undertaken.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites CLSI 2014

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    ISTH 2009 discourages use of comments such as 'borderline' while CLSI 2014 suggests that the use of 'indeterminate' can be useful where a panel of assay results does not permit clear distinction between LA detection or lack thereof.

    “ISTH 2009 discourages use of comments such as “borderline” while CLSI 2014 suggests that the use of “indeterminate” can be useful where a panel of assay results does not permit clear distinction between LA detection or lack thereof.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites ISTH 2009

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites CLSI 2014

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    The FXa inhibitor rivaroxaban interferes with dRVVT analysis for LA more so than aPTT and has a variable, reagent-dependent effect on prothrombin time-based assays.

    “The FXa inhibitor rivaroxaban interferes with dRVVT analysis for LA more so than aPTT and has a variable, reagent-dependent effect on prothrombin time-based assays.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [17]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [75]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [76]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [77]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    The ISTH 2009 recommendation to employ only dRVVT and aPTT is supported by a wealth of evidence that this pairing constitutes a sensitive and specific diagnostic strategy.

    “The ISTH 2009 recommendation to employ only dRVVT and aPTT is not surprising since there is a wealth of evidence, unlikely to be surpassed, that this pairing constitutes a sensitive and specific diagnostic strategy.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    TSVT coupled with ET has been shown to be a sensitive test for detecting LAs in patients receiving rivaroxaban because both venom fractions are prothrombin activators and thus unaffected by FXa inhibition.

    “TSVT coupled with ET has been shown to be a sensitive test for detecting LAs in patients receiving rivaroxaban because both venom fractions are prothrombin activators and thus unaffected by FXa inhibition.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [76]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Premisecitation

    ISTH 2009 does not recommend integrated tests and procedures employing 'VKA-insensitive' snake venoms, suggesting they require further critical evaluation.

    “Integrated tests and procedures employing “VKA-insensitive” snake venoms are not recommended as it is suggested that they require further critical evaluation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites ISTH 2009

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Bridging with LMWH can be employed when discontinuing VKA therapy for LA testing.

    “Bridging with low-molecular-weight heparin (LMWH) can be employed.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites BCSH 2012

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Both ISTH 2009 and CLSI 2014 urge caution when interpreting results on patients receiving UFH, while BCSH 2012 specifies that LA testing should not be undertaken on patients receiving therapeutic doses as it may cause erroneous results.

    “Both ISTH 2009 and CLSI 2014 urge caution when interpreting results on patients receiving UFH, while BCSH 2012 specifies that LA testing should not be undertaken on patients receiving therapeutic doses as it may cause erroneous results.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites ISTH 2009

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites CLSI 2014

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites BCSH 2012

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • There is currently no established gold standard assay or reference plasma for LA detection.

    “As a result, there are currently no established gold standard assays or reference plasmas for LA detection [[6], [7], [8], [9], [10]].”

    From Comparison of different algorithms for lupus anticoagulant detection: a single-center experience (2024) · cites this paper as [6]

    The Abstract says that an absence of gold standards complicates LA detection, and “Which Screening Tests to Use and How Many to Use?” explicitly notes the lack of a gold-standard LA detection method. The paper does not establish the more specific claim that no reference plasma exists; its “Ratios” section discusses variation among normal pooled plasmas instead. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • PNP should be platelet-free, its content of each coagulation factor should be close to 100%, and it should be obtained from at least 20-40 healthy donors.

    “PNP is very important for the standardization of the mixing test; it should be platelet-free, its content of each coagulation factor should be close to 100%, and it should be obtained from at least 20–40 healthy donors (males and females) [9,48].”

    From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [48]

    The Mixing Tests section says that mixing tests use normal pooled plasma (NPP), and Preanalytical Variables says plasma for lupus anticoagulant testing must be platelet-poor. Our copy does not specify that the pooled plasma should have each coagulation factor near 100% or be obtained from 20–40 healthy male and female donors. The donor counts in Generating Reference Intervals/Cutoff Levels concern reference-interval cutoffs, not preparation of the pool; page numbers were unavailable. (LLM, conf=0.79)

    Experimental — accuracy not yet measured

  • Clotting times of screening, mixing, and confirmatory procedures are prone to inter- and intra-assay variability; therefore, it is recommended to normalize these clotting times by generating a ratio between test clotting time and NPP clotting time.

    “Clotting times of screening, mixing, and confirmatory procedures are prone to inter- (between same-principle tests offered by different manufacturers) and intra-assay (between batches of the same reagent) variability [25]; for this reason, it is recommended to normalize a screening, mixing, and confirmatory clotting time, generating a ratio between test clotting time and NPP clotting time [9,36,48”

    From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [48]

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • Technical and practical issues, including test algorithms, interpretation parameters, cutoff values, and methods of interpretation, are problematic in many laboratories.

    “Technical and practical issues, including test algorithms, interpretation parameters, cutoff values, and methods of interpretation, are problematic in many laboratories [6,8,9,21].”

    From Comparison of different algorithms for lupus anticoagulant detection: a single-center experience (2024) · cites this paper as [6]

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.

  • CLSI sample preparation is described as both requiring two spins and permitting one

    Minor

    The text says there is full consensus that double centrifugation is required, and the table lists double centrifugation for CLSI. It also says CLSI permits a single centrifugation when that achieves the required platelet count.

1 of 1

Cites

Flagged first, then by citations

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

Cited by

Sorted by citations

Related

Authors
Moore, G.
Affiliations
St Thomas' Hospital (GB)
Corresponding author
Moore, Gary
ORCID
Moore, Gary
Venue
Seminars in Thrombosis and Hemostasis
Publisher
Georg Thieme Verlag KG
Published
2014-02-05
Volume
40
Issue
02
Pages
163-171
ISSN
  • 0094-6176 (ISSN-L)
  • 1098-9064
DOI
10.1055/s-0033-1364185
OpenAlex
W2084030336
Cited by
148
References
77
Citations by year
2026: 2 · 2025: 3 · 2024: 6 · 2023: 7 · 2022: 14 · 2021: 13 · 2020: 12 · 2019: 23 · 2018: 12 · 2017: 20 · 2016: 15 · 2015: 14 · 2014: 7
FWCI
13.58
Type
journal article
Language
en
Open access
Licence
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 › Surgery › 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
MeSH terms
Anticoagulants, Blood Coagulation Tests, Humans, Reagent Kits, Diagnostic, Sensitivity and Specificity, Reproducibility of Results, Lupus Coagulation Inhibitor, Antiphospholipid Syndrome

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-08.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-08.

Statistics and arithmetic are recomputed, not judged.

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