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Cited by 21Systemic Lupus Erythematosus ResearchBlood Coagulation and Thrombosis MechanismsVasculitis and related conditions

Single or triple positivity for antiphospholipid antibodies in “carriers” or symptomatic patients: Untangling the knot

Open access
Bertin, Daniel, Camoin‐Jau, Laurence, Veit, Véronique, Resseguier, Noémie, Lambert, Mathilde, Buffet Delmas, Pauline, Heim, Xavier, Mège, Jean‐Louis +2 more·2021·Journal of Thrombosis and Haemostasis
DOI 10.1111/jth.15518
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Abstract

Although the triple positivity of antiphospholipid antibodies (aPL) is important for classifying high‐risk patients, interpretation of aPL positivity, namely the lupus anticoagulant (LA), anti‐cardiolipin (aCL), and anti‐beta2‐glycoprotein I autoantibodies (aB2GPI) remains challenging for thrombotic risk stratification.

AI snapshot

Written from the paper’s full text.

TL;DR

In a retrospective Marseille laboratory cohort, triple antiphospholipid antibody (aPL) positivity did not clearly confer greater clinical severity than single anti-cardiolipin (aCL) positivity among symptomatic patients, and asymptomatic “carriers” were common in both groups. The authors propose a high-risk triple profile based on IgG aCL plus IgG aB2GPI plus two positive LA tests or a Rosner Index >27.

Key findings

  • Among 161 selected patients, carriers were common: 37/88 (42%) triple aPL-positive patients and 32/73 (43.8%) single aCL-positive patients had no APS clinical criteria; overall carrier prevalence was 43%.
  • A high-risk triple aPL profile—two positive LA tests (RI >15 and NR >1.2) plus IgG aCL and IgG aB2GPI—was the most prevalent profile (27/88, 30.7%) and was associated with symptomatic status (OR 3.90, 95% CI 1.43–12.01); RI >27 was also associated with APS-related clinical events (OR 3.42, 95% CI 1.23–10.66).
  • In symptomatic patients, triple versus single aCL positivity showed no significant difference in number of clinical events, thrombosis type/localization, recurrence, or relapse; untreated triple (n=11) versus untreated single aCL symptomatic patients (n=22) also showed no difference in thrombotic events (OR 1.01, 95% CI 0.88–1.17) or obstetrical events (OR 0.94, 95% CI 0.83–1.06).
  • Symptomatic triple-positive patients had more combined obstetrical and thrombotic events (OR 5.84, 95% CI 1.46–39.23), more associated autoimmune disease (OR 2.83, 95% CI 1.11–7.78), especially SLE (OR 11.91, 95% CI 2.18–300.20), and higher aCL levels (OR 1.02, 95% CI 1.01–1.03) than single aCL-positive symptomatic patients.

Methods

  • Retrospective study of laboratory results from all patients tested for LA, IgG/IgM aCL, and IgG/IgM aB2GPI at University Hospital of Marseille between 2013 and 2015; from 6500 patients, 161 were selected as triple aPL-positive or single aCL-positive, with 5-year follow-up available for 121.
  • Positivity definitions: LA positive if APTT or dRVVT was positive; aCL or aB2GPI positive if IgG and/or IgM was positive; triple aPL = positive LA + aCL + aB2GPI; single aCL = aCL IgG and/or IgM only; persistence defined beyond 12 weeks.
  • Statistical analysis used R 3.6.0, Student’s t-test or Mann-Whitney test for continuous variables, χ² or Fisher’s test for categorical data, and univariate logistic regression with Firth correction; two-sided P < .05 was significant.

Limitations

  • Stated: ELISA methods for aPL detection are not standardized, so single-method detection may introduce bias; concordance with another aCL assay was 90% on 10 available samples.
  • Stated: high RI was included as a high-risk marker, but the most recent ISTH guidelines no longer recommend RI interpretation for the LA mixing step; samples were analyzed before those guidelines.
  • Stated: only triple aPL- and single aCL-positive patients were compared; single LA, single aB2GPI, or double aPL positivity were not investigated. The authors also note that triple-positive patients were more often anticoagulated, so the absence of severity difference could be due to more aggressive treatment; evident from the text are the retrospective design, incomplete follow-up (121/161), and small numbers in some comparisons.

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

Integrity signals

Registry

Crossref · 10.1111/jth.15518

Cites

27 of 28 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

11 of 19 cited sources checked · 4 supported · 0 flagged · accuracy not yet measured

  • Premisecitation
    § 1 | INTRODUCTION · p. 2

    Persistent aPL positivity can be found in the absence of clinical criteria of APS in patients called 'aPL carriers'.

    “In addition, persistent aPL positivity can also be found in the absence of clinical criteria of APS in patients called 'aPL carriers,' raising the dilemma of initiating or not a primary thromboprophylaxis. 19,20”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [19] 19. Girón-­ González JA, García del Río E, Rodríguez C, Rodríguez-­ Martorell J, Serrano A. Antiphospholipid syndrome and asymptomatic carriers of antiphospholipid antibody: prospective analysis of 404 individuals. J Rheumatol . 2004;31:1560-­ 1567.

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

    • cites [20] 20. Pengo V, Ruffatti A, Legnani C, et al. Incidence of a first thromboembolic event in asymptomatic carriers of high-­ risk antiphospholipid antibody profile: a multicenter prospective study. Blood . 2011;118:4714-­ 4718. source
  • Premisecitation
    § 4 | DISCUSSION · p. 12

    In the literature, among aPL, isolated LA and aB2GPI are generally found to be associated with higher thrombotic risk than aCL.

    “In the literature, 5-­ 8 among the aPL, isolated LA and aB2GPI are generally found to be associated with higher thrombotic risk than aCL.”
    Quote in the paperSubstantial claim3 of 4 sources checked
    • cites [5] 5. Sevim E, Zisa D, Andrade D, et al. Characteristics of antiphospholipid antibody positive patients in AntiPhospholipid syndrome alliance for clinical trials and InternatiOnal networking. Arthritis Care Res . 2020. https://doi.org/10.1002/acr.24468 source

      The Results (page not available in our copy) report that patients with isolated LAC positivity had the highest proportion of vascular events among the single-positive groups. The Discussion says LAC may carry greater thrombosis risk than either aCL or anti-β2GPI. It does not establish that isolated anti-β2GPI carries greater thrombotic risk than aCL. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [6] 6. Gebhart J, Posch F, Koder S, et al. High risk of adverse pregnancy outcomes in women with a persistent lupus anticoagulant. Blood Adv . 2019;3:769-­ 776. source

      The Introduction (page unavailable) says antiphospholipid antibodies are associated with a prothrombotic state, but does not compare the thrombotic risks of isolated LA, anti-β2GPI, and aCL. The Discussion (page unavailable) concerns pregnancy outcomes in LA-positive women and says its findings cannot be generalized to isolated aCL- or anti-β2GPI-positive patients. Searches for the antibody-specific thrombotic-risk comparison found no passage addressing it. (LLM, conf=0.75)

      Experimental — accuracy not yet measured
    • cites [7] 7. Lockshin MD, Kim M, Laskin CA, et al. Prediction of adverse pregnancy outcome by the presence of lupus anticoagulant, but not anticardiolipin antibody, in patients with antiphospholipid antibodies. Arthritis Rheum . 2012;64:2311-­ 2318. source

      The Results and Discussion (page not provided) find that lupus anticoagulant predicts adverse pregnancy outcomes more strongly than anticardiolipin antibody. They do not establish higher thrombotic risk, and anti-β2-glycoprotein I did not predict adverse pregnancy outcomes in this study. Prior thrombosis is examined as a predictor of pregnancy outcome, not as an outcome compared across antibody types. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [8] 8. Galli M, Luciani D, Bertolini G, Barbui T. Anti-­ beta 2-­ glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the anti phospholipid syndrome. Blood . 2003;102:2717-­ 2723. source
  • Findingown data
    § Essentials · p. 2

    Among triple aPL-positive patients, the prevalence of 'carrier' patients was high (43%).

    “We noted a high prevalence of 'carrier' patients (43%) with triple aPL positivity, which led us to question the clinical relevance of this phenotype.”
    Quote in the paperSubstantial claim
  • Findingown data
    § Abstract · p. 1

    Whatever triple or single aPL positivity, the prevalence of 'carrier' patients was high (43%).

    “Whatever triple or single aPL positivity, we found a high prevalence of 'carrier' patients (43%), which led us to question the clinical relevance of the triple aPL positivity.”
    Quote in the paperSubstantial claim
  • Findingown data
    § 3.4 | Comparison between triple-­ positive and single-­ positive patients · p. 10

    In the triple aPL-positive patients, two patients, one symptomatic and one carrier, had a relapse.

    “In the triple aPL-­ positive patients, two patients, one symptomatic and one carrier, had a relapse.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 14
  • Classified as probably not a substantial claim. 19
  • The quote only partly states this claim. 2

  • May combine two claims.

    Premisecitation
    § 1 | INTRODUCTION · p. 2

    Single aPL positivity does not seem to be associated with an elevated risk of thrombosis, except for isolated LA positivity, which has been highly associated with thrombosis.

    “whereas single positivity does not seem to be associated with an elevated risk of thrombosis except for isolated LA positivity that has been highly associated with thrombosis. 18”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [18] 18. Yin D, de Groot PG, Ninivaggi M, Devreese KMJ, de Laat B. Clinical relevance of isolated lupus anticoagulant positivity in patients with thrombotic antiphospholipid syndrome. Thromb Haemost . 2020.121(9):1220-­ 1227. https://doi.org/10.1055/a-­ 1344-­4271 source

      The Results (p. 1) and the section on association with thrombosis (p. 4) strongly associate isolated lupus anticoagulant positivity with thrombosis (OR 7.3, 95% CI 3.3–16.1). The Introduction (p. 2) reports little or no association for other aPLs in studies of myocardial infarction and stroke, but the paper does not establish the broader claim that all other forms of single aPL positivity lack elevated thrombosis risk. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Study design and conductcitation
    § 2.3 | Laboratory tests · p. 3

    LA was determined using two clotting assays as recommended by the 2009 ISTH guidelines.

    “LA was determined using two clotting assays as recommended by the 2009 International Society on Thrombosis and Haemostasis (ISTH) guidelines, 21 which were applicable at the time of the study: APTT by Diagnostica Stago and dRVVT by HYPHEN BioMed. 21”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [21] 21. Pengo V, Tripodi A, Reber G, et al. Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. Update of the guidelines for lupus anticoagulant detection. Subcommittee on Lupus Anticoagulant/ Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost . 2009;7:1737-­ 1740. source

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

    Premisecitation
    § 1 | INTRODUCTION · p. 2

    aCL are generally regarded as less symptomatic than LA or aB2GPI.

    “which implies that aCL are generally regarded as less symptomatic than their conventional aPL counterparts.”
    Quote in the paperNot a substantial claim3 of 4 sources checked
    • cites [5] 5. Sevim E, Zisa D, Andrade D, et al. Characteristics of antiphospholipid antibody positive patients in AntiPhospholipid syndrome alliance for clinical trials and InternatiOnal networking. Arthritis Care Res . 2020. https://doi.org/10.1002/acr.24468 source

      The Discussion (page not provided) says LAC positivity may be a stronger risk factor for thrombosis and pregnancy morbidity than positivity for either aCL or anti-β2GPI. It does not say that aCL is less symptomatic than anti-β2GPI, so it supports only the comparison with LAC. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [6] 6. Gebhart J, Posch F, Koder S, et al. High risk of adverse pregnancy outcomes in women with a persistent lupus anticoagulant. Blood Adv . 2019;3:769-­ 776. source

      The Discussion (page unavailable) calls LA a major risk factor for pregnancy complications, which lends limited support to distinguishing it from aCL. But the Results say that neither aCL nor aβ2GPI antibody levels appeared predictive in this LA-positive cohort, and the Discussion cautions against generalizing to patients with isolated aCL or aβ2GPI. The paper therefore does not support the broader claim that aCL is generally less symptomatic than both. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [7] 7. Lockshin MD, Kim M, Laskin CA, et al. Prediction of adverse pregnancy outcome by the presence of lupus anticoagulant, but not anticardiolipin antibody, in patients with antiphospholipid antibodies. Arthritis Rheum . 2012;64:2311-­ 2318. source

      The Results and Discussion report that lupus anticoagulant (LAC) predicts adverse pregnancy outcomes more strongly than aCL in the pregnant patients studied. They do not place aCL below anti-β2-GP-I: both failed to predict adverse pregnancy outcomes without LAC. The study also concerns pregnancy outcomes, not symptoms generally. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [8] 8. Galli M, Luciani D, Bertolini G, Barbui T. Anti-­ beta 2-­ glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the anti phospholipid syndrome. Blood . 2003;102:2717-­ 2723. source

  • Classified as probably not a substantial claim.

    Premisecitation
    § 4 | DISCUSSION · p. 12

    APS is considered heterogeneous not only in aPL profile but also in disease manifestations and potentially in physiopathology.

    “APS is considered heterogeneous not only in aPL profile but also in the disease manifestations and potentially in the physiopathology. 26”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [26] 26. Fickentscher C, Magorivska I, Janko C, et al. The pathogenicity of Anti-­ β 2GP1-­ IgG autoantibodies depends on Fc glycosylation. J Immunol Res . 2015;2015:638129. source

  • May combine two claims.

    Study design and conductcitation
    § 4 | DISCUSSION · p. 12

    The samples were analyzed before publication of the new guidelines and interpreted according to the guidelines applicable at that time.

    “However, the samples were analyzed before the publication of these new guidelines and therefore interpreted according to the guidelines that were applicable at this time. 21”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [21] 21. Pengo V, Tripodi A, Reber G, et al. Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. Update of the guidelines for lupus anticoagulant detection. Subcommittee on Lupus Anticoagulant/ Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost . 2009;7:1737-­ 1740. source

  • May combine two claims.

    Findingown data
    § Abstract · p. 1

    In symptomatic patients, phenotype and therapeutic anticoagulation differ according to the number of positive aPL.

    “In symptomatic patients, we demonstrated differences in the phenotype of patients and their therapeutic anticoagulation according to the number of positive aPL”
    Quote in the paperSubstantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingown data
    § Abstract · p. 1

    In symptomatic patients, there was no significant difference between single aCL-positive and triple aPL-positive patients in the number of clinical events, type or localization of thrombosis, recurrence, or relapse.

    “we did not find differences in the number of clinical events, recurrence, or relapse, even in the absence of treatment.”
    Quote in the paperSubstantial claim

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

    Findingown data
    § Biological profile of triple positive patients · p. 11

    No treatment was administered before in single aCL-positive patients, except for one SinS patient treated by rivaroxaban.

    “No treatment was administered before, except for one patient (SinS), treated by rivaroxaban.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § 3.3 | Differences between 'symptomatic' and 'carriers' in single aCL-­ positive patients · p. 9

    In the two groups with single aCL positivity, the IgG isotype represented the main isotype without significant clinical association.

    “In the two groups with single aCL positivity, the IgG isotype represented the main isotype without significant clinical association.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § 2.3 | Laboratory tests · p. 7

    IgG aB2GPI <15.5 U/ml was present in 10 (27%) carrier triple aPL patients and 9 (18%) symptomatic triple aPL patients (p=0.29; OR 1.73; CI 0.62-4.89).

    “| < 15.5 U/ml | 10 (27%) | 9 (18%) | 0.29 (OR 1.73; CI 0.62-­ 4.89) |”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Findingown data
    § 3.1 | High prevalence of asymptomatic 'carriers' in triple-­ positive patients · p. 7

    Over a 2-year period, 88 patients presenting triple positivity (LA, IgG and/or IgM aCL, and IgG and/or IgM aB2GPI) were selected.

    “Over a 2-­ year period, 88 patients presenting a triple positivity, defined as the association of LA, IgG and/or IgM aCL, and IgG and/or IgM aB2GPI were selected.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data
    § 3.3 | Differences between 'symptomatic' and 'carriers' in single aCL-­ positive patients · p. 9

    No significant difference was observed for the other parameters between SinS and SinC.

    “No significant difference was observed for the other parameters.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § 2.3 | Laboratory tests · p. 7

    IgG aB2GPI <8 U/ml was present in 7 (19%) carrier triple aPL patients and 5 (10%) symptomatic triple aPL patients (p=0.22; OR 2.15; CI 0.63-7.85).

    “| < 8 U/ml | 7 (19%) | 5 (10%) | 0.22 (OR 2.15; CI 0.63-­ 7.85) |”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § 3.2 | High-­ risk aPL profile in triple-­ positive patients · p. 9

    In the triple aPL-positive symptomatic group, there was a trend of significance for RI (OR 2.57, 95% CI 0.92-7.55) and for aCL IgG (OR 2.96, 95% CI 0.93-10.47).

    “In the triple aPL-­ positive symptomatic group, a trend of significance was found for RI and for aCL IgG, with OR at, respectively, 2.57 (95% CI: 0.92-­ 7.55) and at 2.96 (95% CI: 0.93- ­ 10.47).”
    Quote in the paperSubstantial claim

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

    Findingown data
    § 3.2 | High-­ risk aPL profile in triple-­ positive patients · p. 8

    Overall, 15 aPL profiles were identified in the study.

    “Overall, we identified 15 aPL profiles in our study and analyzed, for each, the number of symptomatic and asymptomatic patients as”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § 3.4 | Comparison between triple-­ positive and single-­ positive patients · p. 10

    Seven patients presented a first symptomatic event or relapse with thrombotic event or obstetrical complications: two with triple aPL positivity and five with single aCL positivity.

    “Seven patients presented first symptomatic event or relapse with thrombotic event or obstetrical complications, two patients with triple aPL positivity, and five with single aCL positivity.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § 4 | DISCUSSION · p. 11

    Single aCL-positive carriers are significantly less persistent than single aCL-positive symptomatic patients, in contrast to triple-positive carriers.

    “In addition, we showed that single aCL-­ positive carriers are significantly less persistent than symptomatic patients, in contrast to triple-­ positive carriers.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § 3.4 | Comparison between triple-­ positive and single-­ positive patients · p. 10

    In symptomatic patients, no significant difference was found in the percentage of clinical events, thrombosis type (venous or arterial), or obstetric complications according to single aCL or triple aPL positivity.

    “No significant difference was found in the percentage of clinical events, thrombosis type (venous or arterial), or obstetric complications”
    Quote in the paperSubstantial claim

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

    Findingown data
    § 2.3 | Laboratory tests · p. 7

    dRVVT NR <1.2 was present in 1 (3%) carrier triple aPL patients and 1 (2%) symptomatic triple aPL patients (p=1.00; OR 1.43; CI 0.06-36.94).

    “| < 1.2 | 1 (3%) | 1 (2%) | 1.00 (OR 1.43; CI 0.06-­ 36.94) |”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given
    § 2.2 | Data collection · p. 3

    All thrombotic events were objectively confirmed using relevant techniques.

    “All thrombotic events were objectively confirmed using relevant techniques.”
    Quote in the paperSubstantial claim

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

    Premisecitation
    § 4 | DISCUSSION · p. 12

    In the most recent ISTH guidelines, interpretation of the mixing step in LA testing by the RI is no longer recommended.

    “In the most recent ISTH guidelines the interpretation of the mixing step in LA testing by the RI is no longer recommended. 27”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [27] 27. Devreese KMJ, Groot PG, Laat B, et al. 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 de tection and interpretation. J Thromb Haemost . 2020;18:2828-­ 2839. How to cite this article: Bertin D, Camoin- ­ Jau L, Veit V, et al. Single or triple positivity for antiphospholipid antibodies in 'carriers' or symptomatic patients: Untangling the knot. J Thromb Haemost . 2021;19:3018-­ 3030. https://doi. org/10.1111/jth.15518

      Not checked in the free run.

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

    Study design and conductnone given
    § 2.4 | Statistical analysis · p. 7

    Firth's correction for logistic regression was applied to minimize analytical bias caused by small samples.

    “Firth's correction for logistic regression was applied to minimize the analytical bias caused by small samples.”
    Quote in the paperNot a substantial claim

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

    Premisecitation
    § 4 | DISCUSSION · p. 12

    Pengo et al. proposed the concept that triple-positive patients were at high risk of thrombosis.

    “As early as 2005, Pengo et al. proposed the concept that triple posi -tive patients were at high-­ risk of thrombosis. 10”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] 10. Pengo V, Biasiolo A, Pegoraro C, Cucchini U, Noventa F, Iliceto S. Antibody profiles for the diagnosis of antiphospholipid syndrome. Thromb Haemost . 2005;93:1147-­ 1152. source

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

    Interpretationnone given
    § 4 | DISCUSSION · p. 12

    The studied population is representative of a laboratory daily practice.

    “the studied population is representative of a laboratory daily practice.”
    Quote in the paperNot a substantial claim

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

    Premisecitation
    § 4 | DISCUSSION · p. 12

    In the literature, dRVVT is described as the most specific, sensitive, and robust test to detect LA.

    “In the literature, dRVVT is described as the most specific, sen sitive, and robust test to detect LA. 24”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] 24. Pengo V, Bison E, Banzato A, Zoppellaro G, Jose SP, Denas G. Lupus anticoagulant testing: diluted russell viper venom time (dRVVT). Methods Mol Biol . 2017;1646:169-­ 176. source

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

    Study design and conductnone given
    § 4 | DISCUSSION · p. 12

    In this study, persistence of aPL was analyzed using the same method.

    “in our study, persistence of aPL was analyzed using the same method.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § 4 | DISCUSSION · p. 12

    A nationwide prospective study on 119 asymptomatic carriers showed that triple positivity is a risk factor for future thrombotic events, especially in patients with an associated autoimmune disease.

    “A nationwide prospective study performed on 119 asymptomatic carriers showed that triple positivity is a risk factor for future thrombotic events, espe cially in patients with an associated autoimmune disease. 17”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] 17. Mustonen P, Lehtonen KV, Javela K, Puurunen M. Persistent antiphospholipid antibody (aPL) in asymptomatic carriers as a risk factor for future thrombotic events: a nationwide prospective study. Lupus . 2014;23:1468-­ 1476. source

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

    Study design and conductown data
    § 3.4 | Comparison between triple-­ positive and single-­ positive patients · p. 10

    A 5-year clinical follow-up was available for 75% (121/161) of patients.

    “A 5-­ year clinical follow-­ up was available for 75% (121/161) of patients (Table 1)”
    Quote in the paperNot a substantial claim

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

    Study design and conductreasoning
    § 4 | DISCUSSION · p. 12

    aPL detection with a single method may introduce a bias.

    “the aPL detection with a single method may also introduce a bias.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: ELISA methods for aPL detection are not standardized.

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

    Study design and conductnone given
    § 4 | DISCUSSION · p. 12

    Patients were consecutively enrolled.

    “patients were consecutively enrolled”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning
    § 4 | DISCUSSION · p. 12

    It was challenging to compare the aPL profile regarded as the most symptomatic (triple aPL positivity) with the one regarded as the less symptomatic (single aCL positivity).

    “Therefore, it was challenging to compare the aPL profile regarded as the most symptomatic (triple aPL positivity) with the one regarded as the less symptomatic (single aCL positivity).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data
    § 4 | DISCUSSION · p. 12

    The thrombotic risk does not necessarily increase with the number of positive tests or with an elevated aPL titer.

    “In conclusion, this study showed that the thrombotic risk does not necessarily increase with the number of positive tests or with an elevated aPL titer”
    Quote in the paperSubstantial claim

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

    Study design and conductreasoning
    § 4 | DISCUSSION · p. 12

    Patients presenting single LA or aB2GPI positivity or double aPL positivity were not investigated.

    “Those presenting single LA or aB2GPI positivity or double aPL positivity were not investigated and could be explored in another study.”
    Quote in the paperSubstantial claim
33 of 33

  • The paper relies on this without support.

    ELISA methods for aPL detection are not standardized.

    “given the fact that ELISA methods for aPL detection are not standardized”
1 of 1

Claims other papers make about this one

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

  • aPL profiling also involves consideration of antibody titers since higher titers are associated with higher risk.

    “aPL profiling also involves consideration of antibody titers since higher titers are associated with higher risk [7,8,30,31].”

    From Triple-positive antiphospholipid syndrome does not guarantee positivity in each lupus anticoagulant assay (2023) · cites this paper as [30]

    The Discussion (p. 12) concludes that thrombotic risk does not necessarily increase with an elevated aPL titer, contrary to the claim's general association between higher titers and higher risk. The Results (p. 9) found only a trend, not a statistically significant association, for aCL IgG at a higher threshold. (LLM, conf=0.88)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • Positivity with both assays may identify higher risk.

    “Positivity with both assays may identify higher risk.”

    From Triple-positive antiphospholipid syndrome does not guarantee positivity in each lupus anticoagulant assay (2023) · cites this paper as [30]

    The Laboratory tests section (p. 3) identifies two assays for lupus anticoagulant, APTT and dRVVT. The Discussion (pp. 11–12) proposes positivity on both tests as part of a profile for identifying higher-risk carriers, but that profile also requires positive IgG aCL and IgG aB2GPI. The source does not establish that positivity on the two assays alone identifies higher risk. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Bertin et al. found LA positivity in dRVVT and APTT accompanied by elevated IgG aCL and aβ2GPI to be the most common aPL pattern in patients with APS.

    “Bertin et al. found LA positivity in dRVVT and APTT accompanied by elevated IgG aCL and aβ2GPI to be the most common aPL pattern in patients with APS [30].”

    From Triple-positive antiphospholipid syndrome does not guarantee positivity in each lupus anticoagulant assay (2023) · cites this paper as [30]

    Section 3.2 (p. 9) identifies positivity on both LA tests with IgG aCL and IgG aB2GPI as the most prevalent profile among the triple-aPL-positive patients studied (27/88, 30.7%). The paper says this profile was associated with symptomatic triple-positive patients, but does not establish that it is the most common pattern among APS patients generally; the group studied also included asymptomatic carriers. Section 2.3 (p. 3) identifies the two LA tests as APTT and dRVVT. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Single LA assay repertoires are still in use and risk missing not only single-positive APS where isolated persistent LA is a risk factor, but also identification of triple-positive patients who require different management.

    “Single LA assay repertoires are still in use and risk missing not only single-positive APS where isolated persistent LA is a risk factor [11,30], but also identification of triple-positive patients who require different management.”

    From Triple-positive antiphospholipid syndrome does not guarantee positivity in each lupus anticoagulant assay (2023) · cites this paper as [30]

    The Introduction (p. 2) says isolated LA positivity is highly associated with thrombosis, supporting the risk-factor point to which the citation is attached. The Discussion (p. 12) says the study did not investigate single-LA-positive patients, so its own findings do not establish the risk specifically for persistent isolated LA. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Bertin et al. found that LA positivity with both dRVVT and APTT combined with elevated IgG aCL and aβ2GPI represented a high risk of thrombotic events in asymptomatic carriers.

    “Bertin et al. found that LA positivity with both dRVVT and APTT combined with elevated IgG aCL and aβ2GPI represented a high risk of thrombotic events in asymptomatic carriers [30].”

    From Triple-positive antiphospholipid syndrome does not guarantee positivity in each lupus anticoagulant assay (2023) · cites this paper as [30]

Self-check

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

  • Incorrect percentage for symptomatic patients below the dRVVT threshold

    Minor

    The two symptomatic counts in this threshold comparison total 51. Thus, 30 patients represent 58.82%, which rounds to 59%, not the reported 60%.

    Reported 60 · recomputed 58.823529

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Sevim, 2020, Characteristics of antiphospholipid antibody positive patients in AntiPhospholipid syndrome alliance for clinical trials and InternatiOnal networking, Arthritis Care Res

Cited by

Sorted by citations

Related

Authors
Bertin, D., Camoin‐Jau, L., Veit, V., Resseguier, N., Lambert, M., Buffet Delmas, P., Heim, X., Mège, J., Morange, P., & Bardin, N.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Aix-Marseille Université (FR)
  • Assistance Publique Hôpitaux de Marseille (FR)
  • Inserm (FR)
Corresponding author
Bertin, Daniel
ORCID
Venue
Journal of Thrombosis and Haemostasis
Publisher
Elsevier BV
Published
2021-12
Volume
19
Issue
12
Pages
3018-3030
ISSN
1538-7836 (ISSN-L)
DOI
10.1111/jth.15518
OpenAlex
W3196650592
Semantic Scholar
6686eaea1709a5c8e0ad88c15371935bc9a09e11
Cited by
21
References
28
Citations by year
2026: 2 · 2025: 1 · 2024: 12 · 2023: 2 · 2022: 4
FWCI
2.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Thrombosis and Haemostasis (publishedVersion)
  • PubMed (publishedVersion)
  • HAL AMU (submittedVersion)
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
antiphospholipid antibodies, triple positivity, lupus anticoagulant, anti-beta2-glycoprotein I antibodies, thrombotic risk stratification, anticoagulation, recurrent thrombosis
MeSH terms
Humans, Retrospective Studies, Lupus Coagulation Inhibitor, Antiphospholipid Syndrome, Antibodies, Antiphospholipid, Antibodies, Anticardiolipin, beta 2-Glycoprotein I

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 2026-10-25.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-25.

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Statistics and arithmetic are recomputed, not judged.

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