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Cited by 9Systemic Lupus Erythematosus ResearchBlood Coagulation and Thrombosis MechanismsVasculitis and related conditions

Lupus Anticoagulant Detection under the Magnifying Glass

Open access
Molinari, Angelo Claudio, Martini, Tiziano, Banov, Laura, Ierardi, Antonella, Leotta, Marzia, Strangio, Alessandra, Santoro, Rita Carlotta·2023·Journal of Clinical Medicine
DOI 10.3390/jcm12206654PMC PMC10607820
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Abstract

Diagnosis of antiphospholipid syndrome (APS) requires the presence of a clinical criterion (thrombosis and/or pregnancy morbidity), combined with persistently circulating antiphospholipid antibodies (aPL). Lupus anticoagulant (LA) is one of the three laboratory parameters (the others being antibodies to either cardiolipin or β2-glycoprotein I) that defines this rare but potentially devastating condition. For the search for aCL and aβ2-GP-I, traditionally measured with immunological solid-phase assays (ELISA), several different assays and detection techniques are currently available, thus making these tests relatively reliable and widespread. On the other hand, LA detection is based on functional coagulation procedures that are characterized by poor standardization, difficulties in interpreting the results, and interference by several drugs commonly used in the clinical settings in which LA search is appropriate. This article aims to review the current state of the art and the challenges that clinicians and laboratories incur in the detection of LA.

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review examines the current state of the art and the practical pitfalls in laboratory detection of lupus anticoagulant (LA), one of the three laboratory criteria for antiphospholipid syndrome. It walks through patient selection and timing, preanalytical variables, the three-step screening/mixing/confirmatory procedure, assay choice and cut-offs, interference from anticoagulants and other inhibitors, diagnostic algorithms, and reporting.

Key findings

  • LA detection relies on functional coagulation assays that are poorly standardized, hard to interpret, and subject to drug interference, unlike the more reliable solid-phase immunoassays for anticardiolipin (aCL) and anti-β2-glycoprotein-I (aβ2-GP-I) antibodies.
  • The recommended approach is a three-step sequence — screening (aPTT-based assay such as silica clotting time, plus dRVVT), mixing, and confirmatory (increased phospholipid concentration) — with dRVVT described as the most sensitive and specific test; ISTH recommends at least two screening tests based on different principles, and a screening is considered positive if either is positive.
  • Reported epidemiology: aPL tests are positive in approximately 13% of stroke patients, 11.5% with myocardial infarction, 9.5% with deep vein thrombosis, and 6% with pregnancy morbidity; the annual risk of a first thrombosis in persistently aPL-positive patients without other risk factors is <1%, rising to as high as 5% with systemic autoimmune disease or additional thrombotic risk factors. General-population prevalence is unknown but cited as 1–5%.
  • Interference is pervasive: factor VIII elevation can shorten aPTT and cause false negatives; C-reactive protein can prolong phospholipid-dependent tests and cause false positives; all anticoagulants except snake-venom-derived prothrombin activator assays affect LA testing, with DOACs producing both false positives and false negatives (rivaroxaban affecting screening more than confirmatory, apixaban the opposite). Up to 20% of patients with factor VIII inhibitors can show a positive dRVVT.

Methods

Narrative review of the literature on LA detection, covering preanalytical phase (citrate collection at 9:1, double centrifugation to a platelet count <10 × 10⁹/L, freeze/thaw limits), the three-step diagnostic procedure, assay selection, cut-off derivation, anticoagulant interference, and diagnostic algorithms. No systematic search strategy, inclusion criteria, or primary data collection are reported; the paper synthesizes existing guidelines (ISTH, CLSI, BSH) and cited studies. Cut-off guidance is described: ISTH recommends in-house cut-offs at the 99th percentile from at least 120 healthy individuals, while CLSI/BSH use a parametric ±2 SD approach; manufacturer-provided cut-offs may be used if verified against 20–40 healthy subjects.

Limitations

The paper states no formal limitations section. Evident from the text: it is a narrative review without a systematic search or evidence-grading framework, so selection of cited studies is not transparent; several key points are presented as matters of ongoing debate rather than settled evidence (e.g., LA testing in anticoagulated patients, the role of mixing tests, cut-off methodology, and the "lupus cofactor" phenomenon whose incidence "is not exactly known"); and the authors note that the true prevalence of aPL positivity in the general population is unknown because population-based studies are absent.

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

Integrity signals

Registry

Crossref · 10.3390/jcm12206654

Cites

106 of 106 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

48 of 104 cited sources checked · 27 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Several drugs (antibiotics, antiarrhythmics, chlorpromazine) and vaccines (hepatitis B) can occasionally be associated with LA positivity.

    “Furthermore, several drugs (antibiotics, antiarrhythmics, chlorpromazine) and vaccines (hepatitis B) can occasionally be associated with a LA positivity [24].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [24] Martirosyan, 2019, Environmental Triggers of Autoreactive Responses: Induction of Antiphospholipid Antibody Formation, Front. Immunol. source
  • Premisecitation

    Asymptomatic persistent carriers of LA and other antiphospholipid antibodies have a higher risk of future thromboembolic events.

    “it has been demonstrated that asymptomatic persistent carriers of LA and of the other antiphospholipid antibodies have a higher risk of future thromboembolic events [11,12].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [11] Pengo, 2011, Incidence of a First Thromboembolic Event in Asymptomatic Carriers of High-Risk Antiphospholipid Antibody Profile: A Multicenter Prospective Study, Blood source
    • cites [12] Mustonen, 2014, Persistent Antiphospholipid Antibody (APL) in Asymptomatic Carriers as a Risk Factor for Future Thrombotic Events: A Nationwide Prospective Study, Lupus source
  • Premisecitation

    Reagents containing a low concentration of phospholipids are more sensitive to LA.

    “a general principle is that reagents containing a low concentration of phospholipids are more sensitive to LA [8].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [8] Tripodi, A. (2021). Diagnostic Challenges on the Laboratory Detection of Lupus Anticoagulant. Biomedicines, 9. source
  • Premisecitation

    Recent clinical trials of patients with APS randomized to receive VKA or rivaroxaban showed a significant excess of thrombosis recurrence in rivaroxaban patients.

    “Recent clinical trials of patients with APS randomized to receive VKA or rivaroxaban (a direct factor Xa inhibitor) showed a significant excess of thrombosis recurrence in rivaroxaban patients [65,66].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [65] Pengo, 2018, Rivaroxaban vs. Warfarin in High-Risk Patients with Antiphospholipid Syndrome, Blood source
    • cites [66] Vidal, 2019, Rivaroxaban Versus Vitamin K Antagonist in Antiphospholipid Syndrome, Ann. Intern. Med. source
  • Premisecitation

    Evidence shows that there is great inter-laboratory variability even when using the same analytic platform.

    “even if evidence shows that there is a great inter-laboratory variability even when using the same analytic platform [61,63].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [61] Tripodi, 2017, Variability of Cut-off Values for the Detection of Lupus Anticoagulants: Results of an International Multicenter Multiplatform Study, J. Thromb. Haemost. source
    • cites [63] Moore, 2020, Lupus Anticoagulant Assay Cut-offs Vary between Reagents Even When Derived from a Common Set of Normal Donor Plasmas, J. Thromb. Haemost. source
  • Classified as probably not a substantial claim. 23
  • May combine two claims. 30
  • The quote only partly states this claim. 1

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

    Premisecitation

    It is recommended to select an aPTT that uses silica as activator.

    “It is recommended to select an aPTT that uses silica as activator [9].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [9] Devreese, 2020, Guidance from the Scientific and Standardization Committee for Lupus Anticoagulant/Antiphospholipid Antibodies of the International Society on Thrombosis and Haemostasis: Update of the Guidelines for Lupus Anticoagulant Detection and Interpretation, J. Thromb. Haemost. source

  • May combine two claims.

    Premisecitation

    dRVVT is not influenced by factor VIII levels, as factor X is directly activated by the diluted Russell's viper venom.

    “while dRVVT is not influenced by factor VIII levels, as factor X is directly activated by the diluted Russell’s viper venom [7].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [7] Vandevelde, A., and Devreese, K.M.J. (2022). Laboratory Diagnosis of Antiphospholipid Syndrome: Insights and Hindrances. J. Clin. Med., 11. source

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

    Premisecitation

    For the search for aCL and aβ2-GP-I, several different assays and detection techniques are currently available, making these tests relatively reliable and widespread.

    “For the search for aCL and aβ2-GP-I, traditionally performed by solid-phase immunoassays (ELISA), several different assays and detection techniques are currently available, thus making these tests relatively reliable and widespread [7].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [7] Vandevelde, A., and Devreese, K.M.J. (2022). Laboratory Diagnosis of Antiphospholipid Syndrome: Insights and Hindrances. J. Clin. Med., 11. source

      Section 4.1 confirms that aCL and aβ2GPI testing traditionally uses ELISA and that several alternative techniques and commercial assays are available. It does not support the inference that this variety makes the tests relatively reliable: the same section reports high inter-assay variability and poor agreement between assays. It says automated testing is increasingly used in laboratories, but not universally available. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Clot waveform analysis (CWA) is little used in laboratories and its clinical utility is still being evaluated.

    “However, it is little used in laboratories and its clinical utility is still being evaluated [41].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [41] Kanouchi, 2021, Diagnostic analysis of lupus anticoagulant using clot waveform analysis in activated partial thromboplastin time prolonged cases: A retrospective analysis, Health Sci. Rep. source

      The Introduction (page not provided) says the authors assessed CWA’s clinical value for detecting lupus anticoagulant, and the Discussion calls for further studies using other analyzers. This supports the claim that its clinical utility is still being evaluated, but our copy does not say CWA is little used in laboratories. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    dRVVT is recommended for its specificity and robustness.

    “dRVVT is recommended for its specificity and robustness [9].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [9] Devreese, 2020, Guidance from the Scientific and Standardization Committee for Lupus Anticoagulant/Antiphospholipid Antibodies of the International Society on Thrombosis and Haemostasis: Update of the Guidelines for Lupus Anticoagulant Detection and Interpretation, J. Thromb. Haemost. source

  • May combine two claims.

    Premisecitation

    In theory, coagulation factors contained in PNP will correct the prolongation of the screening test if affected by a deficiency of one or more factors; if an inhibitor is present, the clotting time will remain prolonged.

    “In theory, the coagulation factors contained in PNP will correct the prolongation of the screening test, restoring a clotting time that falls in the range of normality, if affected by a deficiency of one (or more) factors; if an inhibitor is present, the clotting time will remain prolonged [46,47].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [46] 2008, Laboratory Testing for Lupus Anticoagulants: Preexamination Variables, Mixing Studies, and Diagnostic Criteria, Semin. Thromb. Hemost. source
    • cites [47] Moore, G. (2016). Current Controversies in Lupus Anticoagulant Detection. Antibodies, 5. source

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

    Premisecitation

    ISTH guidelines recommend that confirmatory test(s) must be performed by increasing the concentration of phospholipids used in the screening test(s).

    “ISTH guidelines recommend that confirmatory test(s) must be performed by increasing the concentration of phospholipids used in the screening test(s) [9].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [9] Devreese, 2020, Guidance from the Scientific and Standardization Committee for Lupus Anticoagulant/Antiphospholipid Antibodies of the International Society on Thrombosis and Haemostasis: Update of the Guidelines for Lupus Anticoagulant Detection and Interpretation, J. Thromb. Haemost. source

  • Classified as probably not a substantial claim.

    Premisecitation

    Testing for LA is appropriate only in patients in whom there is a reasonable suspicion of APS.

    “Testing for LA is appropriate only in those patients in which there is a reasonable suspicion of APS [9]”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [9] Devreese, 2020, Guidance from the Scientific and Standardization Committee for Lupus Anticoagulant/Antiphospholipid Antibodies of the International Society on Thrombosis and Haemostasis: Update of the Guidelines for Lupus Anticoagulant Detection and Interpretation, J. Thromb. Haemost. source

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

    Premisecitation

    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].”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [9] Devreese, 2020, Guidance from the Scientific and Standardization Committee for Lupus Anticoagulant/Antiphospholipid Antibodies of the International Society on Thrombosis and Haemostasis: Update of the Guidelines for Lupus Anticoagulant Detection and Interpretation, J. Thromb. Haemost. source

      Section 3.4 (page not available) specifies minimal residual platelets and approximately 100% (>80%) clotting-factor activity for PNP. It says the donor minimum is difficult to define but treats at least 40 as reasonable; it does not support a minimum as low as 20 or specify male and female donors. “Platelet-free” is also stronger than its wording. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [48] Moore, 2014, Recent Guidelines and Recommendations for Laboratory Detection of Lupus Anticoagulants, Semin. Thromb. Hemost. source

      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

  • Classified as probably not a substantial claim.

    Premisecitation

    Current guidelines recommend avoiding LA testing during an acute thrombotic event or an acute episode (e.g., an infection).

    “Current guidelines recommend avoiding LA testing during an acute thrombotic event or an acute episode (e.g., an infection) [9]”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [9] Devreese, 2020, Guidance from the Scientific and Standardization Committee for Lupus Anticoagulant/Antiphospholipid Antibodies of the International Society on Thrombosis and Haemostasis: Update of the Guidelines for Lupus Anticoagulant Detection and Interpretation, J. Thromb. Haemost. source

      Section 2.2 (page unavailable) says LA results obtained during the acute phase, including soon after a thrombotic event, should be interpreted with caution because of possible test interference. It does not recommend avoiding testing altogether; it says acute-phase testing may be needed. Section 4 (page unavailable) notes that infection can cause transient LA positivity and recommends confirming a positive result after 12 weeks, not avoiding testing during infection. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

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

    Premisecitation

    ISTH guidelines recommend using at least two tests as screening, based on different principles: a LA-sensitive test derived from aPTT (such as SCT) and dRVVT.

    “The most recent ISTH guidelines [9] recommend using at least two tests as screening, based on different principles:A LA-sensitive test derived from aPTT (such as SCT, silica clotting time);The dRVVT (dilute Russell viper venom time).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [9] Devreese, 2020, Guidance from the Scientific and Standardization Committee for Lupus Anticoagulant/Antiphospholipid Antibodies of the International Society on Thrombosis and Haemostasis: Update of the Guidelines for Lupus Anticoagulant Detection and Interpretation, J. Thromb. Haemost. source

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

    Premisecitation

    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”
    Quote in the paperSubstantial claim4 of 6 sources checked
    • cites [25] Moore, 2022, Testing for Lupus Anticoagulants, Semin. Thromb. Hemost. source
    • cites [9] Devreese, 2020, Guidance from the Scientific and Standardization Committee for Lupus Anticoagulant/Antiphospholipid Antibodies of the International Society on Thrombosis and Haemostasis: Update of the Guidelines for Lupus Anticoagulant Detection and Interpretation, J. Thromb. Haemost. source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [36] Keeling, 2012, Guidelines on the Investigation and Management of Antiphospholipid Syndrome, Br. J. Haematol. source

      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
    • cites [48] Moore, 2014, Recent Guidelines and Recommendations for Laboratory Detection of Lupus Anticoagulants, Semin. Thromb. Hemost. source

      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
    • cites [54] Bailly, 2020, Guidelines for Lupus Anticoagulant Testing in South Africa, J. Med. Lab. Sci. Technol. South. Afr. source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [55] Limper, 2019, Diagnosing and Treating Antiphospholipid Syndrome: A Consensus Paper, Neth. J. Med.

  • May combine two claims.

    Premisecitation

    LA detection is based on functional coagulation assays that are characterized by poor standardization, difficulty in interpreting the results, and interference by several drugs commonly used in the clinical setting in which LA search is appropriate.

    “In contrast, LA detection is based on functional coagulation assays that are characterized by poor standardization, difficulty in interpreting the results, and interference by several drugs commonly used in the clinical setting in which LA search is appropriate [8].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [8] Tripodi, A. (2021). Diagnostic Challenges on the Laboratory Detection of Lupus Anticoagulant. Biomedicines, 9. source

  • May combine two claims.

    Premisecitation

    CLSI and BSH guidelines employ a "parametric" approach assuming a Gaussian distribution of LA results, using a reference range of ±2 standard deviations from the mean value.

    “CLSI and BSH guidelines [15,36], on the other hand, employ a “parametric” approach assuming a Gaussian distribution of LA results, using a reference range of ±2 standard deviations from the mean value”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [15] Wayne, P. (2014). H60-A Laboratory Testing for the Lupus Anticoagulant, Approved Guideline, Clinical and Laboratory Standards Institute.

      Not checked in the free run.

    • cites [36] Keeling, 2012, Guidelines on the Investigation and Management of Antiphospholipid Syndrome, Br. J. Haematol. source

      The Lupus anticoagulant testing section says laboratories have historically used mean + 2 SD as an LA-positive cutoff for normally distributed data, and that most UK laboratories use the corresponding 97.5th centile. It does not prescribe a ±2 SD reference range or say that LA results must be Gaussian; it also notes a contrasting 99th-centile recommendation. This source does not establish what the separately cited CLSI guideline uses. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • The authors state this as an assumption: LA results follow a Gaussian distribution.

  • May combine two claims.

    Premisecitation

    The combination of TSVT/ET demonstrated good sensitivity and specificity in LA detection in VKA-treated patients in an international multicenter multiplatform study, but is not routinely utilized in laboratories at present.

    “the use of the combination of TSVT/ET (Taipan snake venom time/ecarin time), which in an international multicenter multiplatform study demonstrated good sensitivity and specificity in LA detection in VKA-treated patients [28], but is not routinely utilized in laboratories at present”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [28] Moore, 2021, International Multicenter, Multiplatform Study to Validate Taipan Snake Venom Time as a Lupus Anticoagulant Screening Test with Ecarin Time as the Confirmatory Test: Communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies, J. Thromb. Haemost. source

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

    Premisecitation

    ISTH SSC guidance stated that "LA testing in patients on anticoagulation should be undertaken with the cognizance that anticoagulants may prolong the clotting time of the tests used for LA detection and that this effect may give rise to false-positive or false-negative LA".

    “A recent guidance from the Scientific and Standardization Committee (SSC) for lupus anticoagulant/antiphospholipid antibodies of the ISTH [14] stated that “LA testing in patients on anticoagulation should be undertaken with the cognizance that anticoagulants may prolong the clotting time of the tests used for LA detection and that this effect may give rise to false-positive or false-negative LA”.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [14] Tripodi, 2020, Lupus Anticoagulant Detection in Anticoagulated Patients. Guidance from the Scientific and Standardization Committee for Lupus Anticoagulant/Antiphospholipid Antibodies of the International Society on Thrombosis and Haemostasis, J. Thromb. Haemost. source

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

    Premisecitation

    The premature interruption of the TRAPS trial led the EMA to warn against the use of DOACs in APS patients, recommending the exclusion of APS in patients with acute thrombosis after unspecified causes for whom treatment with a DOAC is indicated, shifting anticoagulation to VKA if there is an anti-phospholipids-antibodies positivity.

    “The premature interruption of the TRAPS trial [65] led the EMA (European Medicines Agency) to warn against the use of DOACs in APS patients, recommending the exclusion of APS in patients with acute thrombosis after unspecified causes for whom treatment with a DOAC is indicated, shifting anticoagulation to VKA if there is an anti-phospholipids-antibodies positivity [67].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [65] Pengo, 2018, Rivaroxaban vs. Warfarin in High-Risk Patients with Antiphospholipid Syndrome, Blood source
    • cites [67] European Medicines Agency PRAC (2023, August 08). Recommendations on Signals. Available online: https://www.ema.europa.eu/en/documents/prac-recommendation/pracrecommendations-signals-adopted-8-11-april-2019-prac-meeting_en.pdf.

      Not checked in the free run.

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

    Premisecitation

    ISTH guidelines recommend a mixing-test-specific cut-off over ICA.

    “Therefore, ISTH guidelines recommend a mixing-test-specific cut-off over ICA [9].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [9] Devreese, 2020, Guidance from the Scientific and Standardization Committee for Lupus Anticoagulant/Antiphospholipid Antibodies of the International Society on Thrombosis and Haemostasis: Update of the Guidelines for Lupus Anticoagulant Detection and Interpretation, J. Thromb. Haemost. source

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

    Premisecitation

    ISTH SSC guidelines recommend measuring anti-factor-Xa activity in heparin-treated patients to verify if the UFH or LMWH effect is at therapeutic interval; in this case, LA testing can be performed using assays containing heparin neutralizers.

    “However, ISTH SSC guidelines recommend measuring anti-factor-Xa activity in heparin-treated patients, to verify if the UFH or LMWH effect is at therapeutic interval; in this case, LA testing can be performed using assays containing heparin neutralizers [14].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [14] Tripodi, 2020, Lupus Anticoagulant Detection in Anticoagulated Patients. Guidance from the Scientific and Standardization Committee for Lupus Anticoagulant/Antiphospholipid Antibodies of the International Society on Thrombosis and Haemostasis, J. Thromb. Haemost. source

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

    Premisecitation

    Some works have shown that the values from the parametric approach do not respect the Gaussian probability model.

    “(even if some works have shown that these values do not respect the Gaussian probability model [61,62])”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [61] Tripodi, 2017, Variability of Cut-off Values for the Detection of Lupus Anticoagulants: Results of an International Multicenter Multiplatform Study, J. Thromb. Haemost. source
    • cites [62] Pradella, 2013, Cooperation Experience in a Multicentre Study to Define the Upper Limits in a Normal Population for the Diagnostic Assessment of the Functional Lupus Anticoagulant Assays, Clin. Chem. Lab. Med. CCLM source

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

    Premisecitation

    In clinical practice, enrolment of 120 subjects is difficult; an alternative could be the use of manufacturer-provided cut-offs, assuming that these derive from a correct procedure in terms of population selection, statistical method, etc.

    “In clinical practice, the enrolment of 120 subjects is difficult (especially for small laboratories); an alternative could be the use of manufacturer-provided cut-offs (assuming that these derive from a correct procedure in terms of population selection, statistical method, etc.).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [8] Tripodi, A. (2021). Diagnostic Challenges on the Laboratory Detection of Lupus Anticoagulant. Biomedicines, 9. source

      Section 7, “Cut-Off Values,” says enrolling 120 or more healthy subjects is impractical, especially for small laboratories, and identifies manufacturer cut-offs as a possible alternative. But it requires those cut-offs to be checked locally for accuracy using 20 or 40 subjects; assuming the manufacturer used a correct procedure is not the condition the paper gives. The section also cautions against using cut-offs determined elsewhere without local validation. (LLM, conf=0.90)

      Experimental — accuracy not yet measured
    • The authors state this as an assumption: Manufacturer-provided cut-offs derive from a correct procedure in terms of population selection, statistical method, etc.

  • May combine two claims.

    Premisecitation

    Both DOAC removal strategies (absorbents and filtration) can provide incomplete drug removal or influence the clotting times, resulting in possible false positives and false negatives in LA testing.

    “Both removal strategies can provide an incomplete drug removal or influence the clotting times, resulting in possible false positives and false negatives in LA testing [81,82,85,86].”
    Quote in the paperSubstantial claim2 of 4 sources checked
    • cites [81] Tripodi, 2021, Impact of a Commercially Available DOAC Absorbent on Two Integrated Procedures for Lupus Anticoagulant Detection, Thromb. Res. source
    • cites [82] Devreese, 2020, Direct Oral Anticoagulant Adsorption: Impact on Lupus Anticoagulant Testing—Review of the Literature and Evaluation on Spiked and Patient Samples, J. Thromb. Haemost. source

      The Essentials and Conclusion report that DOAC-Stop adsorption can leave residual drug and produce erroneous lupus anticoagulant results; section 3.2.3 also reports changes in clotting times after treatment. The paper does not establish the claim for the other named strategy, filtration. Its discussion of false-negative results concerns DOAC interference, not a demonstrated effect of filtration or adsorption. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [85] Sevenet, 2020, Evaluation of DOAC Filter, a New Device to Remove Direct Oral Anticoagulants from Plasma Samples, Int. J. Lab. Hematol. source
    • cites [86] Farkh, 2021, A Diagnostic Solution for Lupus Anticoagulant Testing in Patients Taking Direct Oral FXa Inhibitors Using DOAC Filter, Front. Med. source

  • May combine two claims.

    Premisecitation

    The first approach (ISTH in-house cut-offs) is characterized by increased specificity and a statistically inevitable reduction of sensitivity, partially counterbalanced by the use of two assays.

    “The first approach is characterized by an increased specificity (that reduces false positives) and a statistically inevitable reduction of sensitivity (partially counterbalanced by the use of two assays) [7].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [7] Vandevelde, A., and Devreese, K.M.J. (2022). Laboratory Diagnosis of Antiphospholipid Syndrome: Insights and Hindrances. J. Clin. Med., 11. source

  • May combine two claims.

    Premisecitation

    All DOACs prolong dRVVT in screening and confirmatory procedures, with rivaroxaban affecting screening more than confirmatory (increasing potential false positives) and opposite apixaban action (increasing potential false negatives).

    “all DOACs prolong dRVVT in screening and confirmatory procedures, with rivaroxaban affecting screening more than confirmatory (increasing potential false positives) and opposite apixaban action (increasing potential false negatives) [73,74,75,76,77,78].”
    Quote in the paperSubstantial claim2 of 6 sources checked
    • cites [73] Favaloro, 2019, Laboratory Testing for Lupus Anticoagulant (LA) in Patients Taking Direct Oral Anticoagulants (DOACs): Potential for False Positives and False Negatives, Pathology source
    • cites [74] Reda, 2020, Functional Lupus Anticoagulant Testing in a Large Retrospective Cohort of Thrombosis Patients with Direct Oral Anticoagulants, Sci. Rep. source

      The Results (Effect of anticoagulant drugs on functional LA testing; page unavailable) report that rivaroxaban levels correlate with both dRVVT screening and confirmatory tests and with an increased dRVVT ratio, supporting the concern about false positives. They do not establish that all DOACs prolong both tests: the study evaluated rivaroxaban and apixaban, and found no significant correlation between apixaban levels and the dRVVT ratio. The claimed opposite effect of apixaban and increased potential for false negatives are not supported by these passages. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [75] Hillarp, 2020, Unveiling the Complex Effects of Direct Oral Anticoagulants on Dilute Russell’s Viper Venom Time Assays, J. Thromb. Haemost. source

      The Results and Discussion report that rivaroxaban affected screening more than confirmation in four of six assays and produced false-positive ratios in three. The Introduction notes that apixaban may cause false-negative results, but the Discussion says apixaban showed a similar, less pronounced pattern to rivaroxaban in some assays; opposite effects depended on the reagent. The paper does not establish that every DOAC prolongs both procedures in every assay. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [76] Martinuzzo, 2018, False-Positive Lupus Anticoagulant Results by DRVVT in the Presence of Rivaroxaban Even at Low Plasma Concentrations, Int. J. Lab. Hematol. source
    • cites [77] Gay, 2019, Lupus Anticoagulant Diagnosis in Patients Receiving Direct Oral FXa Inhibitors at Trough Levels: A Real-life Study, Int. J. Lab. Hematol. source
    • cites [78] Antovic, 2017, Effects of Direct Oral Anticoagulants on Lupus Anticoagulant Assays in a Real-Life Setting, Thromb. Haemost. source

  • May combine two claims.

    Premisecitation

    VKA cause an acquired deficiency of factors II, VII, IX, and X that can give false positives in screening tests and false negatives in mixing tests.

    “These drugs cause an acquired deficiency of factors II, VII, IX, and X that can give false positives in screening tests and false negatives in mixing tests [7].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [7] Vandevelde, A., and Devreese, K.M.J. (2022). Laboratory Diagnosis of Antiphospholipid Syndrome: Insights and Hindrances. J. Clin. Med., 11. source

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

    Premisecitation

    ISTH guidelines expressly recommend not using cut-off values established elsewhere, but using "in house" cut-off values deriving from a sufficiently large population of healthy individuals (at least 120), with the cut-off determined as the 99th percentile.

    “ISTH guidelines expressly recommend not using cut-off values established elsewhere, but using “in house” cut-off values deriving from a sufficiently large population of healthy individuals (at least 120): the value of cut-off is determined to be the 99th percentile [9].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [9] Devreese, 2020, Guidance from the Scientific and Standardization Committee for Lupus Anticoagulant/Antiphospholipid Antibodies of the International Society on Thrombosis and Haemostasis: Update of the Guidelines for Lupus Anticoagulant Detection and Interpretation, J. Thromb. Haemost. source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    False-negative mixing tests can arise from reagent sensitivity and specificity to LA; some LAs that are positive in screening tests with both aPTT and dRVVT show positivity in the mixing test for one test but not the other.

    “False-negatives mixing tests can also arise for reasons other than dilution, such as reagents’ sensitivity and specificity to LA: some LAs, undoubtedly positive in screening tests with both aPTT and dRVVT, show positivity in the mixing for one test but not for the other [105,106].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [105] Devreese, 2007, Interpretation of Normal Plasma Mixing Studies in the Laboratory Diagnosis of Lupus Anticoagulants, Thromb. Res. source
    • cites [106] Moore, 2017, Application of Different Lupus Anticoagulant Diagnostic Algorithms to the Same Assay Data Leads to Interpretive Discrepancies in Some Samples, Res. Pract. Thromb. Haemost. source

      The Results and Discussion (page unavailable) report different false-negative mixing-test rates for dRVVT and dAPTT and identify reagent composition as a possible contributor to mixing-test results beyond antibody potency. The paper does not establish that samples positive on both screening tests were mixing-test positive on one assay but negative on the other, or that reagent sensitivity and specificity caused that particular pattern. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Even if factor VIII inhibitors require incubation to express their activity, if present at very high titre, they immediately neutralize factor VIII of NPP in the aPTT mixing procedure, making them indistinguishable from LA.

    “Even if these inhibitors require incubation to express their activity (2 h at 37 °C), if they are present at very high titre, they immediately neutralize factor VIII of NPP in the aPTT mixing procedure, thus making them indistinguishable from LA [8].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [8] Tripodi, A. (2021). Diagnostic Challenges on the Laboratory Detection of Lupus Anticoagulant. Biomedicines, 9. source

      Section 11 says factor VIII inhibitors generally exert their activity after incubation for 2 hours at 37 °C, but high-potency inhibitors are likely to inhibit factor VIII in pooled normal plasma immediately during mixing, making them indistinguishable from LA. The citing sentence states immediate neutralization as certain, whereas the source qualifies it as likely. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Italian, British, and international guidelines on the diagnosis of AHA indicate the need to exclude the presence of LA and investigate an isolated prolonged aPTT that does not correct with a mixing test.

    “Italian, British, and international guidelines on the diagnosis of AHA indicate the need to exclude the presence of LA and investigate an isolated prolonged aPTT that does not correct with a mixing test [101,102,103].”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [101] Coppola, 2022, Acquired Haemophilia A: Italian Consensus Recommendations on Diagnosis, General Management and Treatment of Bleeding, Blood Transfus. source
    • cites [102] Collins, 2013, Diagnosis and Management of Acquired Coagulation Inhibitors: A Guideline from UKHCDO, Br. J. Haematol. source
    • cites [103] Tiede, 2020, International Recommendations on the Diagnosis and Treatment of Acquired Hemophilia A, Haematologica source

      The Diagnosis and Mixing tests sections support investigating unexplained, isolated APTT prolongation and considering LA in the differential diagnosis. But the recommendations say LA testing may be performed, not that LA must be absent; they also note that LA can coexist with AHA. A mixing test that does not correct warrants further investigation but cannot itself establish or exclude AHA. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Interpretationreasoning

    The stepwise procedure can reduce costs by avoiding unnecessary mixing and confirmatory tests if the screening test is normal.

    “Therefore, this stepwise procedure can reduce costs, avoiding unnecessary mixing and confirmatory tests if the screening test is normal”
    Quote in the paperSubstantial claim

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

    Interpretationnone given

    The specificity of LA screening test is hard to define, because of the difficulty of finding a test able to certainly individuate the "real" true positives (the "true LA").

    “The specificity of LA screening test is hard to define, because of the difficulty of finding a test able to certainly individuate the “real” true positives (the “true LA”).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The heterogeneity of LA antibodies and the variability of their effect in coagulation assays explain why there is not a single test sensitive to all LA, and a combination of several assays is necessary for correct diagnosis.

    “The heterogeneity of these antibodies and the variability of the effect they provoke in several coagulation assays explain why there is not a single test that is sensitive to all the LA, but it is necessary to use a combination of several assays for a correct diagnosis [25].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [25] Moore, 2022, Testing for Lupus Anticoagulants, Semin. Thromb. Hemost. source

  • May combine two claims.

    Premisecitation

    Silica clotting time (SCT) is a phospholipid-dependent test that contains colloidal silica as activator and a very low concentration of phospholipid, making it very sensitive to LA.

    “Silica clotting time (SCT) is a phospholipid-dependent test that contains colloidal silica as activator and a very low concentration of PL [37], thus making it very sensitive to LA.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [37] (2023, July 28). Practical Haemostasis. Available online: https://practical-haemostasis.com/.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Commercial lyophilized plasmas show the same characteristics of home-made PNP and can be employed for performing the mixing test.

    “There are several commercial lyophilized plasmas that show the same characteristics of home-made PNP and can be employed for performing the mixing test [49].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [49] AICE (Associazione Italiana Centri Emofilia) Quality Laboratory Working Group (2022). Consensus Document: Procedures for Hemostasis Laboratory, Mixing Test and Measurement of Factors VIII and IX, AICE, Italian Association of Hemophilia Centres.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    aPS/PT can be considered a surrogate of LA as these antibodies generally present in triple-positive patients and are responsible for the majority of LA activity.

    “Test for anti-phosphatydilserine/prothrombin antibodies (aPS/PT), which can be considered a surrogate of LA as these antibodies generally present in triple-positive patients (determining the so-called “tetra-positivity”) and are responsible for the majority of LA activity [88,89].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [88] Pengo, 2018, Lupus Anticoagulant Identifies Two Distinct Groups of Patients with Different Antibody Patterns, Thromb. Res. source
    • cites [89] Cattini, 2020, Tetra Positive Thrombotic Antiphospholipid Syndrome: Major Contribution of Anti-phosphatidyl-serine/Prothrombin Antibodies to Lupus Anticoagulant Activity, J. Thromb. Haemost. source

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

    Interpretationnone given

    dRVVT is the most sensitive and specific test to detect LA.

    “dRVVT is the most sensitive and specific test to detect LA.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims. The quote only partly states this claim.

    Interpretationnone given

    LA increases thrombotic risk and is a significant risk factor for APS, with patients with LA being at increased risk of deep vein thrombosis, pulmonary embolism, and stroke.

    “Despite its name, LA actually increases thrombotic risk and is a significant risk factor for APS.”
    • Also stated in: § 10. Discussion and Conclusions · plain
      “Patients with LA are at an increased thrombotic risk, including deep vein thrombosis (DVT), pulmonary embolism (PE), and stroke.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    dRVVT is very useful for excluding the presence of LA, as this test is less sensitive to factor VIII deficiency; however, up to 20% of patients with factor VIII inhibitors show a positive dRVVT.

    “dRVVT is very useful for excluding the presence of LA, as this test is less sensitive to factor VIII deficiency; however, it has been demonstrated that up to 20% of patients with factor VIII inhibitors show a positive dRVVT [40].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] Tiede, 2014, Laboratory Diagnosis of Acquired Hemophilia A: Limitations, Consequences, and Challenges, Semin. Thromb. Hemost. source

  • May combine two claims.

    Premisecitation

    Chromogenic factor assays (CSA) do not suffer from these interferences, showing normal clotting factor activities.

    “A fundamental aid in these circumstances comes from performing chromogenic factor assays (CSA) [90], which do not suffer from these interferences, showing normal clotting factor activities [92,96,97].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [92] Wahl, 1998, A Chromogenic Assay Allows Reliable Measurement of Factor VIII Levels in the Presence of Strong Lupus Anticoagulants, Thromb. Haemost. source
    • cites [96] Chandler, 2003, Comparison of Three Methods for Measuring Factor VIII Levels in Plasma, Am. J. Clin. Pathol. source
    • cites [97] Kitchen, S., Olson, J., and Preston, F.E. (2009). Quality in Laboratory Hemostasis and Thrombosis, John Wiley. source

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

    Interpretationnone given

    LA detection is performed following a three-step approach consisting of screening, mixing, and confirmation.

    “LA detection is performed following a three-step approach that consists of a sequence of three coagulation procedures: screening, mixing, and confirmation.”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    Pregnant individuals with LA are at higher risk of miscarriages, stillbirths, and other pregnancy-related complications due to increased clotting tendency.

    “Pregnant individuals with LA are at a higher risk of miscarriages, stillbirths, and other pregnancy-related complications due to the increased clotting tendency.”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    LA detection is based on functional coagulation assays characterized by poor standardization, difficulty in interpreting results, and interference by several drugs commonly used in the clinical setting in which LA search is appropriate.

    “LA detection is based on functional coagulation assays that are characterized by poor standardization, difficulty in interpreting the results, and interference by several drugs commonly used in the clinical setting in which LA search is appropriate.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    NPP characteristics can influence mixing test results; some NPPs have shorter clotting times, requiring a stronger LA for a mixing test to be positive.

    “Finally, NPP characteristics can influence the results of mixing tests, as some NPPs have shorter clotting times, requiring a stronger LA for a mixing test be positive [107].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [107] Moore, 2017, Reference Interval Mean Clotting Times Should Not Be Used to Calculate Lupus Anticoagulant Mixing Test Ratios Unless They Match the Normal Pooled Plasma Clotting Time, Thromb. Res. source
43 of 43

  • The authors state this as an assumption.

    Manufacturer-provided cut-offs derive from a correct procedure in terms of population selection, statistical method, etc.

    “an alternative could be the use of manufacturer-provided cut-offs (assuming that these derive from a correct procedure in terms of population selection, statistical method, etc.)”

  • The authors state this as an assumption.

    LA results follow a Gaussian distribution.

    “employ a “parametric” approach assuming a Gaussian distribution of LA results”

  • The paper relies on this without support.

    Anticoagulants are able to prolong the clotting time of screening, mixing, and confirmatory tests, making interpretation difficult.

    “Anticoagulants are able to prolong the clotting time of screening, mixing, and confirmatory tests, thus making the interpretation of these results difficult for the clinician (Table 4).”

  • The paper relies on this without support.

    LA can be hard to distinguish from other antibody-mediated coagulation alterations, such as factor VIII autoantibodies characterizing acquired haemophilia A (AHA).

    “LA can be hard to distinguish from other antibody-mediated coagulation alterations, such as factor VIII autoantibodies characterizing acquired haemophilia A (AHA).”

  • The paper relies on this without support.

    LA is one of the key criteria for diagnosing APS, and its presence alongside anticardiolipin and anti-β2 glycoprotein I antibodies helps confirm the diagnosis of APS.

    “LA is one of the key criteria for diagnosing APS. Alongside other antibodies such as anticardiolipin antibodies and anti-β2 glycoprotein I antibodies, the presence of LA helps confirm the diagnosis of APS.”

  • The paper relies on this without support.

    LA positivity can be transient and associated with infectious or phlogistic processes.

    “to avoid transient antibody positivity, such as that associated with infectious or phlogistic processes.”

  • The paper relies on this without support.

    Knowing that a patient has LA can influence treatment decisions, especially for those who have already been diagnosed with autoimmune conditions such as SLE.

    “Knowing that a patient has LA can influence treatment decisions, especially for those who have already been diagnosed with autoimmune conditions such as SLE.”

  • The paper relies on this without support.

    The presence of LA might impact the choice of medications and their dosages, as certain drugs can interact with the hypercoagulable state associated with APS.

    “The presence of lupus anticoagulant might impact the choice of medications and their dosages, as certain drugs can interact with the hypercoagulable state associated with APS.”
8 of 8

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.

  • Confirmatory test is described as both concurrent and subsequent

    Minor

    The description says screening and confirmatory tests are performed together, then says that a confirmatory test follows if needed. The test that follows is therefore inconsistent with the stated order of the procedure.

1 of 1

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Authors
Molinari, A. C., Martini, T., Banov, L., Ierardi, A., Leotta, M., Strangio, A., & Santoro, R. C.
Affiliations
  • Istituto Giannina Gaslini (IT)
  • Ospedale “M. Bufalini” di Cesena (IT)
  • Azienda Ospedaliero-Universitaria "Renato Dulbecco" (IT)
Corresponding author
Martini, Tiziano
ORCID
Venue
Journal of Clinical Medicine
Publisher
MDPI AG
Published
2023-10-20
Volume
12
Issue
20
Pages
6654
ISSN
2077-0383 (ISSN-L)
DOI
10.3390/jcm12206654
PMC
PMC10607820
OpenAlex
W4387823021
Semantic Scholar
a85861de06f8f6c5117f47775b157e6bcb82a27e
Cited by
9
References
106
Citations by year
2026: 3 · 2025: 3 · 2024: 2 · 2023: 1
FWCI
1.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Clinical Medicine (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
Topics
  • Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Vasculitis and related conditions
Keywords
lupus anticoagulant, antiphospholipid syndrome, antiphospholipid antibodies, assay standardization, drug interference

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.

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Statistics and arithmetic are recomputed, not judged.

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