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Cited by 2Systemic Lupus Erythematosus ResearchBlood Coagulation and Thrombosis MechanismsClinical Laboratory Practices and Quality Control

Lupus Anticoagulant Testing in Challenging Situations: Navigating Complexities

Open access
Devreese, Katrien M. J.·2026·International Journal of Laboratory Hematology
DOI 10.1111/ijlh.14490
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Abstract

The laboratory diagnosis of antiphospholipid syndrome (APS) relies on detecting persistent antiphospholipid antibodies (aPL), including lupus anticoagulant (LA) as one of the three laboratory criteria. LA is a well‐established risk factor in APS and the cornerstone of APS diagnosis, identifying triple‐positive patients. LA testing is supported by testing guidelines, but challenges remain with LA measurement, which is complex and susceptible to numerous pitfalls and interferences. A nuanced understanding of the technical and interpretative aspects of LA testing is crucial for accurate diagnosis. Limited to specific patient populations, the timing of testing in relation to clinical events is essential to avoid false results, and only persistent LA positivity is considered diagnostic. Proper sample preparation, choice of assays, test procedure, cutoff values, and strategies to handle anticoagulant therapy interference pose significant challenges in LA testing. While advances in the harmonization of test procedures and testing guidelines have improved diagnostic reliability, the complex nature of LA demands careful consideration of methodological issues and potential interferences, underscoring the importance of expertise and interdisciplinary communication in achieving accurate results. Interpretative comments and close interaction between clinical pathologists and clinicians are mandatory for diagnosis and patient management. This paper will focus on the technical aspects of the laboratory method and the interpretation of LA results in the diagnosis of APS with attention to specific situations where LA testing is difficult.

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review examines the preanalytical, analytical, and postanalytical pitfalls of lupus anticoagulant (LA) testing in antiphospholipid syndrome (APS), focusing on situations where testing is difficult: acute thrombosis, pregnancy, acute-phase inflammation, and anticoagulant therapy. It argues that the three-step procedure (screen, mix, confirm) plus close clinical–laboratory communication is essential to avoid false positive and false negative LA results.

Key findings

  • LA can fluctuate: a prospective observational study of aPL-positive pregnant patients enrolled in late first/early second trimester found 25% of LA-positive patients became negative in the second or third trimester; results obtained during pregnancy or the thrombotic phase should be reassessed after delivery or after the event.
  • CRP interferes with phospholipid-dependent assays, mainly aPTT, prolonging clotting time and potentially causing false positives; elevated FVIII during acute phase can shorten aPTT and cause false negatives. The paper recommends measuring CRP (on citrated sample if no serum), noting fibrinogen as an acute-phase indicator, and adding an interpretive comment advising retesting after the acute phase.
  • In a study of 35% of thrombotic APS patients being single persistent LA positive, LA in single-positive patients was weaker than in triple-positive patients but still clearly positive with a high screen/confirm dRVVT ratio and a positive (uncorrected) mixing test. In a VKA vs non-VKA comparison, more negative (corrected) mixing tests occurred in VKA-treated patients (35% vs 10%), with no evidence LA was weaker by screen/confirm dRVVT ratio.
  • Cutoff values are problematic: calculating in-house cutoffs requires at least 120 normals (not feasible for many labs); multicenter studies show differences between platforms and even with the same normal samples, while one Australian multicenter study found dRVVT cutoffs comparable across sites on one instrument brand, and a single-center study found excellent agreement between in-house and manufacturer cutoffs. TSVT/ET was used by less than 10% of survey participants.

Methods

  • Narrative review by a single author (Devreese), synthesizing international guidance (ISTH-SSC aPL, CLSI H60-A, ACR/EULAR 2023 criteria) and the author's own laboratory practice; no systematic search or primary data collection is described.
  • Covers preanalytical issues (citrated plasma, double centrifugation, freezing within 4 h, platelet-poor < 10 × 10⁹/L, FV < 50% as a sample-quality flag), the three-step test procedure, anticoagulant interference (VKA, DOAC, heparins), cutoff determination, and patient selection.
  • Includes a summary table (Table 1) of challenges in LA detection and a figure (Figure 1) of the three-step procedure in non-anticoagulated, orally anticoagulated, and anticoagulation-status-unknown patients.

Limitations

  • Stated by the paper: the best timing of testing post-thrombosis has yet to be determined; the clinical relevance of an LA disappearing in the mixing step remains unclear; further studies are needed before LA strength can be introduced into risk assessment; no information is available on interference of intravenous immunoglobulins on aPL testing; a ready-made solution for cutoff values is not available and further multicenter efforts are needed; TSVT/ET reagent availability is limited and more standardized reagents require validation in large multicenter studies.
  • Evident from the text: this is a single-author narrative review drawing substantially on the author's own laboratory practice ("in my setting," "in my laboratory") rather than a systematic evidence synthesis; several cited studies are single-center or small, and recommendations are based on international guidance plus expert opinion rather than new primary data.

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

Integrity signals

Registry

Crossref · 10.1111/ijlh.14490

Cites

71 of 71 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 144 cited sources checked · 0 supported · 0 flagged

  • Findingcitation

    In persistent positive LA APS patients, LA positivity expressed as a normalized ratio was weaker in isolated LA-positive patients than the LA activity in triple-positive patients.

    “In persistent positive LA APS patients, we observed that LA positivity, expressed as a normalized ratio, was weaker in isolated LA-positive patients compared with LA activity in triple-positive patients, suggesting that stronger LA better corresponds with a high-risk profile [4].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4]

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

  • Premisecitation

    APS diagnosis relies on detecting persistent antiphospholipid antibodies, including LA as one of the three laboratory criteria.

    “The laboratory diagnosis of antiphospholipid syndrome (APS) relies on detecting persistent antiphospholipid antibodies (aPL), including lupus anticoagulant (LA) as one of the three laboratory criteria.”
    • Also stated in: § 1 | The Role of Lupus Anticoagulant in Antiphospholipid Syndrome · plain
      “Lupus anticoagulant (LA) is one of the laboratory criteria to diagnose antiphospholipid syndrome (APS), a systemic autoimmune disease defined by the presence of antiphospholipid antibodies (aPL).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [4]

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

    • cites [5]

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

  • Premisecitation

    LA positivity identifies high-risk triple-positive APS patients.

    “LA positivity identifies high-risk triple-positive patients [6,7,9]”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [6]

      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.

    • cites [9]

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

  • Premisecitation

    In vitro CRP binds to phospholipids added in the reagent mixture of phospholipid-dependent coagulation assays, prolonging clotting time and potentially generating false positive LA results.

    “As a consequence, in vitro CRP binds to the phospholipids added in the reagent mixture of phospholipid-dependent coagulation assays, prolonging the clotting time and potentially generating false positive 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 [18]

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

  • Premisecitation

    In pregnancy, FVIII levels rise and resolve 6 weeks after delivery postpartum.

    “Also, in pregnancy, FVIII levels rise and resolve 6 weeks after delivery postpartum [25].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25]

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

  • May combine two claims. 39
  • Classified as probably not a substantial claim. 34

  • May combine two claims.

    Premisecitation

    Positive LA in pediatric patient populations is often transient and not associated with clinical APS complications.

    “Studies showed that positive LA in pediatric patient populations is often transient and not associated with clinical complications related to APS.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [21]

      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.

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

    Premisecitation

    Hydroxychloroquine and statins have been used as emerging treatments for APS.

    “Hydroxychloroquine and statins have been used as emerging treatments and are sometimes prescribed to patients with APS with breakthrough manifestations or at high risk of recurrent events [2].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2]

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

  • May combine two claims.

    Interpretationreasoning

    Elevated CRP can suggest possible elevated FVIII levels, with LA missed in the aPTT system.

    “Elevated CRP can suggest possible elevated FVIII levels, with an LA missed in the aPTT system.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Few persistent positive LA were present in COVID-19, and frequent single LA positivity during acute COVID-19 was not clearly related to thrombotic complications.

    “Soon, it became clear that few persistent positive LA were present, and the frequent single LA positivity during (acute phase) COVID-19 infection was not clearly related to thrombotic complications [23,24].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [23]

      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.

  • May combine two claims.

    Premisecitation

    The effect of CRP on dRVVT is contradictory in literature but depends on the reagent used.

    “The effect of CRP on dilute Russell's viper venom time (dRVVT) is contradictory in literature but also depends on the reagent used [17,20].”
    Quote in the paperNot a substantial claim0 of 2 sources 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.

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

    Premisecitation

    Transient LA in children was thought to be linked to viral or bacterial infections, although the underlying mechanism remained uncertain.

    “These LA were thought to be linked to viral or bacterial infections, although the underlying mechanism remained uncertain.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [21]

      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.

    Premisecitation

    CRP interference is mainly observed in aPTT and depends on reagent composition regarding type, concentration, and structure of phospholipids.

    “This is mainly observed in the activated partial thromboplastin time (aPTT) and depends on the reagent composition regarding the type, concentration, and structure of present phospholipids [17,18].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [17]

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

    • cites [18]

      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

    Infections are the most common triggering factor for catastrophic APS.

    “Infections are the most common triggering factor [1,27].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1]

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

    • cites [27]

      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 most recent international guideline on LA detection methodology is from the ISTH-SSC aPL.

    “There are different international guidelines on the methodology of how to detect LA, with the most recent one from the International Society on Thrombosis and Haemostasis Scientific and Standardization Subcommittee on Lupus anticoagulant/ antiphospholipid antibodies (ISTH-SSC aPL) [14].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14]

      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

    In new stroke patients with suspicion of APS, anticoagulant treatment rather than antiplatelet treatment is indicated to prevent recurrent stroke.

    “In new stroke patients with suspicion of APS, anticoagulant treatment rather than antiplatelet treatment is indicated to prevent recurrent stroke [7,14,26].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [7]

      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 [26]

      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 ISTH-SSC guideline provides detailed information on methodology for LA detection and interpretation, aiming for harmonization and increasing uniformity.

    “This guideline provides detailed information on the methodology for LA detection and the interpretation of LA results, aiming for harmonization and increasing uniformity [14].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14]

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

  • May combine two claims.

    Premisecitation

    Although aPL positivity is necessary to establish diagnosis of CAPS in rapidly deteriorating patients, a presumptive clinical diagnosis can be made, allowing empirical treatment before aPL results.

    “Although aPL positivity is necessary to establish the diagnosis of CAPS in rapidly deteriorating patients, a presumptive clinical diagnosis can be made, allowing empirical treatment to be initiated before receipt and interpretation of aPL results [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.

    Premisereasoning

    A sample should be platelet-poor (<10 × 10^9/L) before freezing because in frozen/thawed plasma with residual platelets, aPL can adsorb on platelet membranes and produce false negative LA test results.

    “The sample should be plateletpoor (< 10 × 10 9 /L) before freezing because in frozen/thawed plasma that contains low levels of residual platelets, aPL can potentially adsorb on the platelet membranes and produce false negative LA test results.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Performing the mixing and confirmation test in each sample with a prolonged screening test can avoid false positive LA due to anticoagulant therapy and prevent misdiagnosis of APS and further testing after 3 months.

    “Performing the mixing and confirmation test in each sample with a prolonged screening test can avoid false positive LA due to anticoagulant therapy and prevent misdiagnosis of APS and further testing after 3 months.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    In daily practice, VKA-treated patients are much more prominent than patients with true LA, so the risk of false positives exceeds the risk of false negatives.

    “In daily practice, the population of VKA-treated patients is much more prominent than those with a true LA, meaning that the risk of false positives (assuming that a weak LA disappears in the mixing step) exceeds the risk of false negatives (based on a negative mixing step).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: In daily practice, VKA-treated patients are much more prominent than patients with true LA.

  • May combine two claims.

    Premisecitation

    In single LA-positive patients, LA was weaker compared to triple-positive patients but still clearly positive with high screen/confirm dRVVT ratio and positive mixing test.

    “The LA in the single LA-positive patients was weaker compared to the LA in triple-positive patients (LA, aCL, and aβ2GPI positive) but still clearly positive with a high screen/ confirm dRVVT ratio and with a positive (not corrected) mixing test [4].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4]

      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

    Using algorithms with (automated) reflex testing can enhance the multistep procedure for LA testing and may aid laboratories in evaluating LA results.

    “Using algorithms with (automated) reflex testing can enhance the multistep procedure for LA testing and may aid laboratories in evaluating LA results [42].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42]

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

  • Classified as probably not a substantial claim.

    Premisecitation

    LA is present if one or both test systems are positive in the screening, mixing, and confirmation step.

    “LA is present if one or both test systems are positive in the screening, mixing, and confirmation step.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14]

      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 three-step procedure (screening, mixing, confirmation) is designed to distinguish LA from other reasons for prolonged clotting times.

    “The three steps are designed to distinguish LA from other reasons for prolonged clotting times, as already described 30 years ago [32].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32]

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

  • Classified as probably not a substantial claim.

    Premisecitation

    LA is present if the aPTT and/or dRVVT test system is positive in the screening, mixing, and confirmation step.

    “LA is present if the aPTT and/or dRVVT test system is positive in the screening, mixing, and confirmation step [14].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14]

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

  • May combine two claims.

    Premisecitation

    The cofactor in normal plasma potentiates the inhibitory activity of LA, and the clotting time of the mixing test is longer than the clotting time of the screening test.

    “The cofactor in the normal plasma potentiates the inhibitory activity of LA, and the clotting time of the mixing test is longer than the clotting time of the screening test.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41]

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

  • May combine two claims.

    Premisecitation

    The screening step is prolonged in coagulation factor deficiencies and anticoagulants; the mixing step rules out factor deficiency and indicates an inhibitor; the confirmation step confirms phospholipid dependency.

    “The screening step is also prolonged in the case of coagulation factor deficiencies and anticoagulants; the mixing step rules out a coagulation factor deficiency and indicates an inhibitor, and the confirmation step confirms the phospholipid dependency of the inhibitor [32].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [32]

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

  • Classified as probably not a substantial claim.

    Premisecitation

    A two-test approach involving dRVVT and an LA-sensitive aPTT is recommended by guidelines.

    “A two-test approach involving a dRVVT and an LA-sensitive aPTT is recommended by the guidelines [14].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14]

      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

    In CLSI guidelines, the mixing test is omitted where there is no evidence of other causes of prolonged clotting times or phospholipid dependency is already demonstrated.

    “In the CLSI guidelines, the mixing test is omitted where there is no evidence of other causes of prolonged clotting times or the phospholipid-dependency is already demonstrated by the combination of screening and confirmation step [36].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36]

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

  • May combine two claims.

    Premisecitation

    Performing mixing and confirmation steps simultaneously adds information and is helpful in interpretation where there are discrepant results between mixing and confirmation.

    “Performing both steps simultaneously adds information and is helpful in the interpretation where there are discrepant results between the mixing and confirmation steps [14].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14]

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

  • May combine two claims.

    Premisecitation

    Differences between dRVVT reagents exist but are less marked than for aPTT reagents.

    “There are differences between dRVVT reagents [33,34], but less marked than is for aPTT reagents.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [33]

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

    • cites [34]

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

  • May combine two claims.

    Premisenone given

    All anticoagulants affect the coagulation assays used for LA, but the effects differ based on the type of anticoagulant and the specific assays performed.

    “All anticoagulants affect the coagulation assays used for LA, but the effects differ based on the type of anticoagulant and the specific assays performed.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    aCL and aβ2GPI can be performed on citrated plasma.

    “aCL, aβ2GPI can be performed on citrated plasma [31].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [31]

      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

    The aPTT should be sensitive to LA with suitable composition and low concentration of phospholipids and preferably silica as activator; SCT is an alternative sensitive assay based on contact activation.

    “The aPTT should be sensitive to LA with a suitable composition and low concentration of phospholipids and preferably silica as an activator; a silica clotting time (SCT) is an alternative sensitive assay also based on contact activation [14].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14]

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

  • May combine two claims.

    Premisenone given

    Methods to address the interference caused by DOAC are available, but the effects of VKAs still present a challenge.

    “Methods to address the interference caused by DOAC are available, but the effects of VKAs still present a challenge.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Routine coagulation tests PT/INR, aPTT, and thrombin time provide background information on anticoagulation status.

    “Routine coagulation tests PT/INR, aPTT, and thrombin time provide background information on anticoagulation status.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    The multistep procedure comprising screening, mixing, and confirmation remains in use.

    “Consequently, the multistep procedure, comprising screening, mixing, and confirmation steps, remains in use [14].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14]

      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 ACR/EULAR classification criteria underline the importance of following guidelines with screening, mixing, and confirmation steps.

    “The ACR/EULAR classification criteria underline the importance of following these guidelines with a screening step followed by a mixing and confirmation step [6].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6]

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

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Premisecitation

    It is recommended to perform all three aPL tests (LA, aCL, aβ2GPI) on the same sample.

    “It is recommended to perform all three aPL tests (LA, aCL, aβ2GPI) on the same sample [7].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7]

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

  • Classified as probably not a substantial claim.

    Premisecitation

    In cases where the confirmatory clotting time of undiluted plasma is prolonged, a mixing test with the confirmation assay reagent is recommended.

    “In cases where the confirmatory clotting time of undiluted plasma is prolonged, a mixing test with the confirmation assay reagent is recommended.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14]

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

  • May combine two claims.

    Premisecitation

    ISTH-SSC guidelines do not prioritize the confirmatory test over the mixing test, whereas CLSI recommends screening and confirmation first and mixing only in specific situations.

    “This is why the ISTH-SSC guidelines for LA do not prioritize the confirmatory test over the mixing test, as is recommended by the Clinical and Laboratory Standards Institute (CLSI) guidelines by performing the screening and confirmation step first and performing the mixing step in specific situations only [36].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [36]

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

  • May combine two claims.

    Premisecitation

    The exclusion of anticoagulation cannot be guaranteed and depends on the interval between the admission of low molecular heparins or DOAC and the sampling.

    “However, the exclusion of anticoagulation cannot be guaranteed and depends on the interval between the admission of low molecular heparins or DOAC and the sampling [14,39].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [14]

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

    • cites [39]

      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).

    Premisenone given

    TSVT as a screening assay, in combination with ET as the confirmation assay, is based on snake venom activation of undercarboxylated FII produced during VKA.

    “Taipan snake venom time (TSVT) as a screening assay, in combination with the ecarin time (ET) as the confirmation assay, has been known for many years; both assays are based on snake venom activation of undercarboxylated FII produced during VKA.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    In-house NPP should also be considered as a reagent given batch-to-batch variation.

    “It is important to note that the in-house NPP should also be considered as a reagent given batch-to-batch variation; this is obvious for a commercial NPP that can be used as an alternative to the in-house NPP [14,55].”
    Quote in the paperNot a substantial claim0 of 2 sources 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.

    Premisereasoning

    aPS/PT cannot replace LA testing but can be useful when the LA result is unreliable or difficult to interpret, as in anticoagulated patients.

    “These antibodies cannot replace LA testing but can be useful when the LA result is unreliable or difficult to interpret, as in anticoagulated patients.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Introducing the mixing step with the confirmation reagent helps in VKA-treated patients and also in DOAC-treated patients who often have a prolonged clotting time in the confirmation assay.

    “Introducing the mixing step with the confirmation reagent [14] helps in VKA-treated patients and also in DOACtreated patients who often have a prolonged clotting time in the confirmation assay [14].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14]

      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.

    Premisereasoning

    Pretreating plasma with adsorbents is recommended only for patients receiving DOAC treatment, as it could influence clotting times and potentially lead to false positive or negative results.

    “Pretreating plasma with adsorbents is recommended only for patients receiving DOAC treatment, as it could influence clotting times and potentially lead to false positive or negative results.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisereasoning

    Antibody titer or strength is not currently factored into the conclusion of LA presence.

    “Antibody titer or strength is not currently factored into the conclusion of LA presence.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    TSVT is affected by LA heterogeneity and does not detect every LA.

    “TSVT is, like other LA assays, affected by the LA heterogeneity and does not detect every LA [47].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [47]

      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

    A ready-made solution is not available yet, and further efforts are needed to establish cutoff values per reagent/instrument combination in a multicenter setting.

    “A ready-made solution is not available yet, and further efforts are needed to establish cutoff values per reagent/ instrument combination in a multicenter setting [7].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [7]

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

  • May combine two claims.

    Premisecitation

    In the CLSI procedure, 40 healthy donors are analyzed per reagent batch, and a reference range is calculated.

    “In this procedure promoted in the CLSI guidelines [36], 40 healthy donors are analyzed per reagent batch, and a reference range is calculated.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [36]

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

  • May combine two claims.

    Premisenone given

    DOAC can influence the aPTT and dRVVT assays, resulting in false positive results even at low concentrations of DOAC, making LA testing at least 48 h after the last dose not entirely safe.

    “DOAC can influence the aPTT and dRVVT assays, resulting in false positive results even at low concentrations of DOAC, making LA testing at least 48 h after the last dose not entirely safe.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    The antibody titer or strength of LA is not considered in the conclusion about the presence of LA.

    “However, the antibody titer or strength is not considered in the conclusion for LA presence.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    LA is reported qualitatively (positive/present or negative/absent) on the basis of the combination of the normalized results of the screening, mixing and confirmation steps.

    “LA is finally reported qualitatively (positive/ present or negative/absent) based on the combination of the normalized results of the screening, mixing, and confirmation steps [7,14].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [7]

      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.

  • May combine two claims.

    Premisecitation

    Some LA-specific aPTT and SCT reagents also contain heparin neutralizers, making LA testing reliable if the anti-Xa level is within the therapeutic range.

    “Some LA-specific aPTT and SCT reagents also contain heparin neutralizers, making LA testing reliable if the anti-Xa level is within the therapeutic range [14].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14]

      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.

    Premisereasoning

    Strength of LA (e.g., weak, moderate, strong) is not graded, as prolongation of clotting times does not reliably correlate with clinical relevance.

    “Strength of LA (e.g., weak, moderate, strong) is not graded, as prolongation of clotting times does not reliably correlate with clinical relevance.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    A multicenter study performed in Australia illustrated that cutoff values for dRVVT on one brand of instrument were comparable between the different sites and that the manufacturer's cutoff value for dRVVT resulted in similar performance of LA testing at various sites.

    “In contrast, a multicenter study performed in Australia illustrated that cutoff values for dRVVT on one brand of instrument were comparable between the different sites and that the manufacturer's cutoff value for dRVVT resulted in similar performance of LA testing at various sites [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.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    LA is qualitatively reported as positive/present or negative/absent based on the screening, mixing, and confirmation steps.

    “LA is qualitatively reported as positive/present or negative/absent based on the screening, mixing, and confirmation steps.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In conjunction with aPTT and dRVVT, as a second-line test, TSVT/ET can add value to maximize the detection rate of LA in VKA- and antiXa-DOAC-treated patients but shows interference of heparins and antiIIa DOAC.

    “In conjunction with aPTT and dRVVT, as a second-line test, it can add value to maximize the detection rate of LA in VKA-and antiXa-DOAC-treated patients but shows interference of heparins and antiIIa DOAC [47].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [47]

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

  • May combine two claims.

    Premisecitation

    In VKA-treated patients, mixing patient plasma and NPP in a 1:1 proportion is sufficient to counteract the acquired factor deficiency of VKA therapy but depends on the NPP.

    “In VKA-treated patients, mixing patient plasma and NPP in a 1:1 proportion [14] is sufficient to counteract the acquired factor deficiency of VKA therapy [44] but depends on the NPP [39].”
    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 [44]

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

    • cites [39]

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

  • May combine two claims.

    Premisenone given

    No single LA assay detects all forms of LA because of antibody heterogeneity, so a combination of aPTT and dRVVT is necessary.

    “No single LA assay detects all forms due to antibody heterogeneity; a combination of aPTT and dRVVT is necessary.”
    Quote in the paperSubstantial claim

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

    Interpretationnone given

    APS is a challenging diagnosis because it can be associated with a multitude of clinical symptoms that are often determined by underlying factors not related to aPL, resulting in overdiagnosis.

    “APS is a challenging diagnosis as it can be associated with a multitude of clinical symptoms, often determined by underlying factors not related to aPL, resulting in overdiagnosis.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    One study observed a higher Rosner index (aPTT-based prolongation) in thrombotic triple-positive patients than in triple-positive carriers.

    “One study observed a higher Rosner index (aPTT-based prolongation) in thrombotic triple-positive patients than in triple-positive carriers [59].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [59]

      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 ACR/EULAR criteria include multiple clinical criteria not present in the Sapporo criteria, such as cardiac valve pathology and thrombocytopenia.

    “These include multiple clinical criteria not present in the Sapporo criteria, such as cardiac valve pathology and thrombocytopenia [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.

  • May combine two claims.

    Premisecitation

    Besides in patients with a clinical suspicion of APS, LA is also tested in a workup for prolonged aPTT in patients without a bleeding tendency and as part of the 2019 EULAR/ACR classification criteria for SLE.

    “Beside in patients with a clinical suspicion of APS, LA is also tested in a workup for prolonged aPTT in patients without a bleeding tendency and as part of the 2019 EULAR/ACR classification criteria for SLE [14,64].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [14]

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

    • cites [64]

      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 recently published ACR/EULAR classification criteria include several clinical domains: microvascular and macrovascular thrombosis, obstetric, cardiac valve and hematologic features.

    “Several clinical domains are included in the recently published ACR/ EULAR classification criteria: microvascular and macrovascular thrombosis, obstetric, cardiac valve, and hematologic features [6].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6]

      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

    According to the ACR/EULAR classification criteria, at least one documented clinical criterion must be present as an entry criterion together with a positive aPL (persistent LA and/or moderate/high titer aCL and/or aβ2GPI IgG) within 3 years of the clinical event to classify a patient as an APS patient.

    “According to the ACR/EULAR classification criteria, at least one documented clinical criterion should be present as an entry criterion along with a positive aPL (persistent LA and/or moderate/high titer aCL and/or aβ2GPI IgG) within 3 years of the clinical event to classify a patient as an APS patient [6].”
    Quote in the paperNot a substantial 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. May combine two claims.

    Premisereasoning

    Testing for APS is driven by clinical suspicion, but the varied presentations of APS and other possible causes of thrombosis and pregnancy complications make selecting patients to test difficult.

    “Testing for APS is driven by clinical suspicion, but its varied presentations and other possible causes of thrombosis and pregnancy complications make selecting patients difficult.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Today, LA detection and interpretation remain challenging even with up-to-date international guidelines available.

    “These issues also illustrate that today, LA detection and interpretation remain challenging even with up-to-date international guidelines available.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    A persistent single-positive LA is a risk factor, although it carries a lower risk than triple-positive patients with thrombotic APS.

    “A persistent single-positive LA is a risk factor, although it carries a lower risk compared to triple-positive patients with thrombotic APS [4,[61][62][63].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [4]

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

    • cites [61]

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

    • cites [62]

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

  • May combine two claims.

    Premisecitation

    Persistent positive single LA is assigned a high weight in the 2023 ACR/EULAR classification criteria and is sufficient to fulfill the laboratory criteria.

    “Persistent positive single LA is assigned a high weight in the 2023 ACR/EULAR classification criteria and is sufficient to fulfill the laboratory criteria [6].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6]

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

66 of 66

  • The paper relies on this without support.

    In daily practice, VKA-treated patients are much more prominent than patients with true LA.

    “In daily practice, the population of VKA-treated patients is much more prominent than those with a true LA”

  • The paper relies on this without support.

    Laboratories are not always informed of anticoagulation therapy.

    “One should be aware that laboratories are not always informed of the anticoagulation therapy”

  • The paper relies on this without support.

    Manufacturers often do not reveal the type and concentration of phospholipids in reagents.

    “Manufacturers often do not reveal the type and concentration of phospholipids in the reagents”

  • The paper relies on this without support.

    The existence of thrombosis and pregnancy morbidity is commonly predisposed by factors not related to aPL.

    “The existence of thrombosis and pregnancy morbidity is commonly predisposed by factors not related to aPL.”

  • The paper relies on this without support.

    LA testing is typically referred to more specialized or larger laboratories.

    “LA is a test typically referred to more specialized or larger laboratories.”

  • The paper relies on this without support.

    LA testing is based on clinical suspicion.

    “LA testing is based on clinical suspicion”

  • The paper relies on this without support.

    Accurate diagnosis depends on both laboratory tests and clinical context.

    “Accurate diagnosis depends on both laboratory tests and clinical context.”

  • The paper relies on this without support.

    Testing is warranted only in patients with a high likelihood of APS.

    “Testing is warranted only in patients with a high likelihood of APS.”

  • The paper relies on this without support.

    Single LA is often detected in older people, only on one occasion and without clinical symptoms associated with APS.

    “For instance, single LA is often detected in older people, only on one occasion and without clinical symptoms associated with APS.”

  • The paper relies on this without support.

    Indiscriminate testing of aPL, including LA, results in accidental findings that are often clinically irrelevant.

    “Indiscriminate testing of aPL, including LA, results in accidental findings, often clinically irrelevant.”

  • The paper relies on this without support.

    Clinicians often start with testing for LA and may be unaware of the limitations of the test.

    “Although to diagnose APS the three groups of aPL should be investigated (LA, aCL, and aβ2GPI), clinicians often start with testing for LA and may be unaware of the test limitations.”
11 of 11

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Gray E., 2014, Collaborative Study on the 1st International Reference Panel (PLASMA) for Lupus Anticoagulant Expert Committee on Biological Standardization

Cited by

Sorted by citations

Related

Authors
Devreese, K. M. J.
Affiliations
Ghent University Hospital (BE)
Corresponding author
Devreese, Katrien M. J.
ORCID
Devreese, Katrien M. J.
Venue
International Journal of Laboratory Hematology
Publisher
Wiley
Published
2025-05-16
Volume
48
Issue
2
Pages
281-294
ISSN
  • 1751-5521 (ISSN-L)
  • 1751-553X
DOI
10.1111/ijlh.14490
OpenAlex
W4410445395
Semantic Scholar
405052151c16452770e05c411c65c8f97c87e483
Cited by
2
References
69
Citations by year
2026: 2
FWCI
1.25
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Laboratory Hematology (publishedVersion)
  • PubMed (publishedVersion)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
  • Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
Keywords
lupus anticoagulant, antiphospholipid syndrome, antiphospholipid antibodies, laboratory diagnosis, assay interference, sample preparation, cut-off values, test harmonization, false positives
MeSH terms
Humans, Lupus Coagulation Inhibitor, Antiphospholipid Syndrome, Antibodies, Antiphospholipid

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 2026-10-19.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-19.

Statistics and arithmetic are recomputed, not judged.

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