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Cited by 38Systemic Lupus Erythematosus ResearchBlood Coagulation and Thrombosis MechanismsVasculitis and related conditions

Antiphospholipid patterns predict risk of thrombosis in systemic lupus erythematosus

Open access
Demir, Selcan, Li, Jessica, Magder, Laurence S, Petri, Michelle·2021·Rheumatology
DOI 10.1093/rheumatology/keaa857PMC PMC8328497
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Abstract

Objective: We evaluated which aPL combinations increase the risk of future thrombosis in patients with SLE. Methods: This prospective cohort study consisted of SLE patients who had been tested for all seven aPL (LA, aCL isotypes IgM, IgG and IgA, and anti-β2-glycoprotein I isotypes IgM, IgG and IgA). Pooled logistic regression was used to assess the relationship between aPL and thrombosis. Results: There were 821 SLE patients with a total of 75 048 person-months of follow-up. During the follow-up we observed 88 incident cases of thrombosis: 48 patients with arterial, 37 with venous and 3 with both arterial and venous thrombosis. In individual models, LA was the most predictive of any [age-adjusted rate ratio 3.56 (95% CI 2.01, 6.30), P < 0.0001], venous [4.89 (2.25, 10.64), P < 0.0001] and arterial [3.14 (1.41, 6.97), P = 0.005] thrombosis. Anti-β2-glycoprotein I IgA positivity was a significant risk factor for any [2.00 (1.22, 3.3), P = 0.0065] and venous [2.8 (1.42, 5.51), P = 0.0029] thrombosis. Only anti-β2-glycoprotein I IgA appeared to add significant risk to any [1.73 (1.04, 2.88), P = 0.0362] and venous [2.27 (1.13, 4.59), P = 0.0218] thrombosis among those with LA. We created an interaction model with four categories based on combinations of LA and other aPL to look at the relationships between combinations and the risk of thrombosis. In this model LA remained the best predictor of thrombosis. Conclusion: Our study demonstrated that in SLE, LA remained the best predictor of thrombosis and adding additional aPL did not add to the risk, with the exception of anti-β2-glycoprotein I IgA.

AI snapshot

Written from the paper’s full text.

TL;DR

In a prospective SLE cohort, lupus anticoagulant (LA) remained the strongest predictor of any, venous, and arterial thrombosis, while anti-β2-glycoprotein I IgA was the only other aPL independently associated with any and venous thrombosis. Adding other aPL isotypes generally did not improve prediction beyond LA, except for a non-significant numerical increase when anti-β2-glycoprotein I IgA was added to LA.

Key findings

  • Among 821 SLE patients with 75,048 person-months of follow-up, there were 88 incident thromboses: 48 arterial, 37 venous, and 3 both arterial and venous.
  • LA was most predictive of any thrombosis [age-adjusted RR 3.56 (95% CI 2.01, 6.30), P < 0.0001], venous thrombosis [4.89 (2.25, 10.64), P < 0.0001], and arterial thrombosis [3.14 (1.41, 6.97), P = 0.005].
  • Anti-β2-glycoprotein I IgA positivity was a significant risk factor for any thrombosis [2.00 (1.22, 3.30), P = 0.0065] and venous thrombosis [2.8 (1.42, 5.51), P = 0.0029], and persisted after adjustment for LA for any [1.73 (1.04, 2.88), P = 0.0362] and venous [2.27 (1.13, 4.59), P = 0.0218] thrombosis.
  • In an interaction model, LA remained the best predictor; adding anti-β2-glycoprotein I IgA to LA gave a 2.3-fold risk of any thrombosis versus LA without anti-β2-glycoprotein I IgA, but this did not reach statistical significance (P = 0.1253).

Methods

  • Prospective cohort study using the Hopkins Lupus Cohort, including SLE patients tested for all seven aPL: LA, aCL IgM/IgG/IgA, and anti-β2-glycoprotein I IgM/IgG/IgA.
  • A person-month dataset was constructed, with aPL information from the most recent prior clinic visit; pooled logistic regression was used to assess aPL–thrombosis relationships, adjusted for age at the person-month.
  • Missing DRVVT confirm ratios among visits with DRVVT ≥45 s were imputed using multiple imputation; analyses including LA were run per imputed dataset and pooled with SAS PROC MIANALYZE.

Limitations

  • The authors state that 60% of patients had anti-β2-glycoprotein I measured only once, so they could not compare persistently versus transiently anti-β2-glycoprotein I-positive patients.
  • The authors state that despite the large number of patients, the number of thrombotic events within some categories was small.
  • Evident from the text: aPL exposure was based on the most recent prior visit rather than confirmed persistent positivity, and anti-β2-glycoprotein I was not assessed at every visit, which may misclassify exposure over follow-up.

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

Integrity signals

Registry

Crossref · 10.1093/rheumatology/keaa857

Cites

47 of 47 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

26 of 57 cited sources checked · 15 supported · 0 flagged · accuracy not yet measured

  • Premisecitation
    § Introduction

    Anti-β2-glycoprotein I IgA is a risk factor for the development of APS thrombosis.

    “Recent publications have confirmed that anti-β2-glycoprotein I IgA is a risk factor for the development of APS thrombosis [17–20].”
    Quote in the paperSubstantial claim4 of 4 sources checked
    • cites [17] Murthy, 2013, Value of isolated IgA anti-beta2-glycoprotein I positivity in the diagnosis of the antiphospholipid syndrome, Arthritis Rheum source
    • cites [18] Tortosa, 2017, Incidence of thromboembolic events in asymptomatic carriers of IgA anti β2 glycoprotein-I antibodies, PLoS One source
    • cites [19] Mehrani, 2011, Association of IgA Anti-beta2 glycoprotein I with clinical and laboratory manifestations of systemic lupus erythematosus, J Rheumatol source

      The Discussion reports a significant association between IgA anti-β2-GPI and venous thrombosis in the studied SLE cohort. It does not establish that the antibody predicts the development of thrombosis in patients with APS; the paper describes associations with cumulative thrombotic history, not prospective risk. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [20] Ruiz-García, 2014, Isolated IgA anti-β2 glycoprotein I antibodies in patients with clinical criteria for antiphospholipid syndrome, J Immunol Res source

      The Results (§3.3; page unavailable) report a strong association between IgA antibody positivity and arterial thrombosis in patients meeting clinical APS criteria. But this was a cross-sectional study, and the Discussion (§4; page unavailable) says prospective studies are needed to establish whether the antibodies predict vascular or thromboembolic events. The paper therefore does not confirm that they are a risk factor for the development of thrombosis. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Premisecitation
    § Discussion

    In patients with isolated IgA anti-β2-glycoprotein I positivity, the increased risk for thromboembolic events was observed only in patients with SLE.

    “In a study of patients with isolated IgA anti-β2-glycoprotein I positivity, the increased risk for thromboembolic events was observed only in patients with SLE [37].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [37] Sweiss, 2010, IgA anti-β2-glycoprotein I autoantibodies are associated with an increased risk of thromboembolic events in patients with systemic lupus erythematosus, PLoS One source
  • Premisecitation
    § Introduction

    Large studies found that IgM aCL and IgM anti-β2-glycoprotein I are not associated with thrombotic events.

    “Large studies found that IgM aCL and IgM anti-β2-glycoprotein I are not associated with thrombotic events [9–13].”
    Quote in the paperSubstantial claim2 of 5 sources checked
    • cites [9] Galli, 2003, Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature, Blood source
    • cites [10] Domingues, 2016, Assessment of the independent associations of IgG, IgM and IgA isotypes of anticardiolipin with thrombosis in SLE, Lupus Sci Med source

      The Results report no evidence of an association between elevated IgM anticardiolipin (aCL) and thrombosis in a cohort of 1,390 people with SLE. The paper does not report a thrombosis finding for IgM anti-β2-glycoprotein I, so it supports only the IgM aCL part of the claim. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [11] Mehrani, 2011, IgM anti-β2 glycoprotein I is protective against lupus nephritis and renal damage in systemic lupus erythematosus, J Rheumatol source

      In 796 patients with SLE, the Results (p. 2) report no significant association between IgM anti-β2-GPI and venous or arterial thrombosis. The table (p. 3) likewise shows no significant association between IgM aCL and the listed venous thromboses, stroke, or myocardial infarction. But both antibodies were significantly associated with transient ischemic attack, so the unqualified claim about thrombotic events is too broad. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [12] Galli, 2008, Invitation to a debate on the serological criteria that define the antiphospholipid syndrome, J Thromb Haemost source
    • cites [13] Swadźba, 2007, Revised classification criteria for antiphospholipid syndrome and the thrombotic risk in patients with autoimmune diseases, J Thromb Haemost source
  • Premisecitation
    § Discussion

    In a 5-year follow-up of 248 asymptomatic individuals with isolated IgA anti-β2-glycoprotein I positivity, the presence of anti-β2-glycoprotein I IgA was an independent risk factor for APS events.

    “A 5-year follow-up of 248 asymptomatic individuals with isolated IgA anti-β2-glycoprotein I positivity showed that the presence of anti-β2-glycoprotein I IgA was an independent risk factor for APS events [18].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [18] Tortosa, 2017, Incidence of thromboembolic events in asymptomatic carriers of IgA anti β2 glycoprotein-I antibodies, PLoS One source

      The Abstract (Methods) reports 244 asymptomatic IgA-positive patients, not 248, alongside 221 antibody-negative controls. The Abstract (Objective) specifies a five-year follow-up, and the Results section identifies IgA-aB2GP1 positivity as an independent risk factor for APS events. The finding is supported, but the stated number of positive individuals is incorrect. (LLM, conf=0.95)

      Experimental — accuracy not yet measured
  • Premisecitation
    § Discussion

    In SLE, IgM isotypes were not found to be associated with thrombosis.

    “In SLE, IgM isotypes were not found to be associated with thrombosis [11, 13].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [11] Mehrani, 2011, IgM anti-β2 glycoprotein I is protective against lupus nephritis and renal damage in systemic lupus erythematosus, J Rheumatol source

      The Results and Discussion (p. 2) report that IgM anti-β2-GPI was not significantly associated with venous or arterial thrombosis in patients with SLE; the table on p. 3 likewise shows no significant thrombosis association for IgM anticardiolipin. The claim extends those findings to IgM isotypes generally, which this paper does not establish. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [13] Swadźba, 2007, Revised classification criteria for antiphospholipid syndrome and the thrombotic risk in patients with autoimmune diseases, J Thromb Haemost source
  • Classified as probably not a substantial claim. 26
  • May combine two claims. 20

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

    Premisecitation
    § Introduction

    APS is classified as the development of venous and/or arterial thromboses, and/or pregnancy morbidity, in the presence of persistently raised levels of either LA, aCL or anti-β2-glycoprotein I.

    “APS has been classified as the development of venous and/or arterial thromboses, and/or pregnancy morbidity, in the presence of persistently raised levels of either the LA, aCL or anti-β2-glycoprotein I [1].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [1] Miyakis, 2006, International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS), J Thromb Haemost source

  • Classified as probably not a substantial claim.

    Premisecitation
    § Discussion

    IgA isotypes of aPL were not included in the Sydney APS criteria.

    “IgA isotypes of aPL were not included in the Sydney APS criteria, due to conflicting data on the association with APS manifestations [1].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [1] Miyakis, 2006, International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS), J Thromb Haemost source

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

    Premisecitation
    § Introduction

    The definition of persistent positivity in the Sapporo criteria (1999) was 6 weeks, but was changed in the Sydney criteria (2006) to 12 weeks.

    “The definition of persistent positivity in the Sapporo criteria (1999) [21] was 6 weeks, but was changed in the Sydney criteria (2006) [1] to 12 weeks.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [21] Wilson, 1999, International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop, Arthritis Rheum source
    • cites [1] Miyakis, 2006, International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS), J Thromb Haemost source

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

    Premisecitation
    § Introduction

    aPL were first described in patients with SLE.

    “aPL were first described in patients with SLE [2, 3].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [2] Boey, 1983, Thrombosis in systemic lupus erythematosus: striking association with the presence of circulating lupus anticoagulant, Br Med J (Clin Res Ed) source

      The Introduction says a lupus anticoagulant–related clotting defect in patients with SLE was first recognised in 1952. It also says the first case report was probably from 1946, and it does not establish that antiphospholipid antibodies as a whole were first described in SLE patients. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [3] Harris, 1983, Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus, Lancet source

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

    Premisecitation
    § Introduction

    The Sydney APS classification criteria include the IgG and IgM isotypes as a laboratory criterion.

    “Currently, the Sydney APS classification criteria include the IgG and IgM isotypes as a laboratory criterion [1].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [1] Miyakis, 2006, International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS), J Thromb Haemost source

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

    Premisecitation
    § Discussion

    Since 2012, the IgA isotype of aPL has been accepted as a laboratory criterion for SLE in the SLICC SLE Classification Criteria.

    “Since 2012, the IgA isotype of the aPL has been accepted as a laboratory criterion for SLE in the SLICC SLE Classification Criteria [23].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [23] Petri, 2012, Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus, Arthritis Rheum source

  • Classified as probably not a substantial claim.

    Premisecitation
    § Discussion

    Anti-β2-glycoprotein I IgA is not part of APS classification criteria.

    “The presence of anti-β2-glycoprotein I IgA, which is not a part of APS classification criteria, was also independently associated with thrombosis in SLE patients.”
    • Also stated in: § Discussion · plain
      “IgA isotypes of aPL were not included in the Sydney APS criteria, due to conflicting data on the association with APS manifestations [1].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [1] Miyakis, 2006, International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS), J Thromb Haemost source

  • Classified as probably not a substantial claim.

    Study design and conductcitation
    § Methods

    SLE patients were diagnosed according to revised ACR and SLICC criteria.

    “SLE patients were diagnosed according to revised ACR and SLICC criteria [23, 24].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [23] Petri, 2012, Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus, Arthritis Rheum source
    • cites [24] Tan, 1982, The 1982 revised criteria for the classification of systemic lupus erythematosus, Arthritis Rheum source

  • May combine two claims.

    Premisecitation
    § Introduction

    In the authors' experience, aPL titres in SLE patients can fluctuate over time and contribute risk even at low and moderate titres.

    “In our experience, aPL titres in SLE patients can fluctuate over time and contribute risk even at low and moderate titres [22].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [22] Petri, 2020, Evaluation of different ways to identify persistent positivity of lupus anticoagulant in systemic lupus erythematosus, Lupus Sci Med source

      The Discussion (page unavailable) reports that lupus anticoagulant positivity in patients with SLE was sporadic across visits, supporting fluctuation over time. It also says gradations in lupus anticoagulant testing confer thrombotic risk, but the paper does not establish that low or moderate aPL titres confer risk; its analysis concerns lupus anticoagulant test results rather than aPL titre categories. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation
    § Discussion

    In SLE, aPL often fluctuate and are often at low or moderate titres, which still confer risk.

    “However, in SLE, aPL often fluctuate and are often at low or moderate titres, which still confer risk [41–43].”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [41] Martinez-Berriotxoa, 2007, Transiently positive anticardiolipin antibodies and risk of thrombosis in patients with systemic lupus erythematosus, Lupus source
    • cites [42] Out, 1992, Prospective study of fluctuations of lupus anticoagulant activity and anticardiolipin antibody titre in patients with systemic lupus erythematosus, Ann Rheum Dis source

      The Follow Up section reports that antiphospholipid antibody results fluctuated in patients with SLE. The paper does not establish that titres were often low or moderate, or that low or moderate titres conferred risk; it notes that the observed fluctuations were not accompanied by thrombosis or a change in platelet count. Page numbers are not available in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [43] Inanc, 1998, Anti-beta2-glycoprotein I, anti-prothrombin and anticardiolipin antibodies in a longitudinal study of patients with systemic lupus erythematosus and the antiphospholipid syndrome, Br J Rheumatol source

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

    Premisecitation
    § Discussion

    IgA anti-β2-glycoprotein I antibodies in secondary APS patients showed better utility than that provided by the IgM isotype.

    “IgA anti-β2-glycoprotein I antibodies in secondary APS patients showed better utility than that provided by the IgM isotype [20].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [20] Ruiz-García, 2014, Isolated IgA anti-β2 glycoprotein I antibodies in patients with clinical criteria for antiphospholipid syndrome, J Immunol Res source

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

    Premisecitation
    § Discussion

    The definition of 'persistent positivity' was 6 weeks in the Sapporo criteria (1999) and revised to 12 weeks in the Sydney criteria (2006).

    “The definition of ‘persistent positivity’ was 6 weeks in the Sapporo criteria (1999) [21] and revised to 12 weeks in the Sydney criteria (2006) [1].”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [21] Wilson, 1999, International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop, Arthritis Rheum source
    • cites [1] Miyakis, 2006, International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS), J Thromb Haemost source

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

    Premisecitation
    § Discussion

    Sciascia et al. evaluated 23 possible combinations of aPL profiles in SLE patients and found that combining LA, anti-β2-glycoprotein I and aPS-PT had the best diagnostic accuracy for both thrombosis and pregnancy loss.

    “Sciascia et al. [34] evaluated 23 possible combinations of aPL profiles in SLE patients, and found that combining LA, anti-β2-glycoprotein I and aPS-PT had the best diagnostic accuracy for both thrombosis and pregnancy loss.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [34] Sciascia, 2012, Clinical accuracy for diagnosis of antiphospholipid syndrome in systemic lupus erythematosus: evaluation of 23 possible combinations of antiphospholipid antibody specificities, J Thromb Haemost source

  • May combine two claims.

    Findingown data
    § Results

    The risk of any thrombosis after adding anti-β2-glycoprotein I IgA to LA was 2.3 times the risk for those who had LA without anti-β2-glycoprotein I IgA, but it did not reach statistical significance (P = 0.1253).

    “The risk of any thrombosis after adding anti-β2-glycoprotein I IgA to LA was 2.3 times the risk for those who had LA without anti-β2-glycoprotein I IgA. However, it did not reach statistical significance (P = 0.1253).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Results

    Anti-β2-glycoprotein I IgA numerically increased the risk of venous thrombosis among those with LA, but statistically it was not significant (P = 0.1081).

    “Anti-β2-glycoprotein I IgA numerically increased the risk of venous thrombosis among those with LA, but statistically it was not significant (P = 0.1081).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Results

    aCL IgG, IgM and IgA, and anti-β2-glycoprotein I IgG and IgM positivity were not associated with increased risk of any, venous and arterial thrombosis after adjusting for LA.

    “aCL IgG, IgM and IgA, and anti-β2-glycoprotein I IgG and IgM positivity were not associated with increased risk of any, venous and arterial thrombosis after adjusting for LA.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Results

    aCL IgA showed a higher rate ratio for any thrombosis (RR 3.08, 95% CI 0.75-12.65, P = 0.1195), but it did not reach statistical significance.

    “aCL IgA showed a higher RR [3.08 (0.75, 12.65), P = 0.1195)] for any thrombosis, but it did not reach statistical significance, likely due to the small number of events and the small number with aCL IgA positivity.”
    Quote in the paperNot a substantial claim

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

    Findingown data
    § Results

    There were 821 SLE patients with a complete profile of 7 aPL and a total of 75,048 person-months of follow-up.

    “There were 821 patients with a complete profile of 7 aPL with a total of 75 048 person-months of follow-up.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Results

    During follow-up, there were 88 incident cases of thrombosis: 48 patients with arterial, 37 with venous, and 3 with both arterial and venous thrombosis.

    “Among these patients, there were 88 incident cases of thrombosis: 48 patients with arterial [CVA (n = 20), MI (n = 12), digital ischaemia (n = 8) or other arterial thromboses (n = 8)]; 37 patients with venous thrombosis [DVT/PE (n = 33) or other venous thromboses (n = 4)]; and 3 patients with both arterial and venous thrombosis (1 patient with DVT/PE and other arterial thrombosis, 1 patient with C”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data
    § Conclusion

    In SLE, LA remained the best predictor of thrombosis, and adding additional aPL did not add to the risk, with the exception of anti-β2-glycoprotein I IgA.

    “Our study demonstrated that in SLE, LA remained the best predictor of thrombosis and adding additional aPL did not add to the risk, with the exception of anti-β2-glycoprotein I IgA.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given
    § Methods

    DRVVT measures were excluded if patients were taking anticoagulants (warfarin/heparin).

    “We excluded DRVVT measures if the patients were taking anticoagulants (warfarin/heparin).”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given
    § Methods

    The Hopkins Lupus Cohort is a prospective longitudinal cohort of SLE patients ongoing since 1987.

    “The Hopkins Lupus Cohort is a prospective longitudinal cohort of SLE patients ongoing since 1987.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § Discussion

    IgA anti-β2-glycoprotein I antibodies are thrombogenic and upregulate tissue factor in mice.

    “IgA anti-β2-glycoprotein I antibodies were thrombogenic and upregulated tissue factor in mice [38].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [38] Ruiz-Limon, 2012, IgA anti-β2glycoprotein I antibodies are pathogenetic in a mouse model of APS, Arthritis Rheum

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

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

    Premisecitation
    § Introduction

    In a 10-year prospective study, thrombosis was the cause in 26.7% of SLE patients who died, and was always associated with the presence of aPL.

    “In a 10-year prospective study, thrombosis was found as the cause in 26.7% of SLE patients who died, and was always associated with the presence of aPL [7].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] Cervera, 2003, Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients, Medicine (Baltimore source

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

    Study design and conductnone given
    § Methods

    All rate ratios were adjusted for age at the person month.

    “All rate ratios (RR) were adjusted for age at the person month.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given
    § Methods

    Patients who had a history of thrombosis before their first measurement of anti-β2-glycoprotein I were excluded.

    “Patients who had a history of thrombosis before their first measurement of anti-β2-glycoprotein I were excluded.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Discussion

    Anti-β2-glycoprotein I IgA antibodies are frequently seen in SLE patients, with a high association with thrombosis.

    “Anti-β2-glycoprotein I IgA antibodies are frequently seen in SLE patients, with a high association with thrombosis [36].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [36] Fanopoulos, 1998, High frequency of abnormal levels of IgA anti-beta2-glycoprotein I antibodies in patients with systemic lupus erythematosus: relationship with antiphospholipid syndrome, J Rheumatol

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

    Study design and conductown data
    § Methods

    Among visits with DRVVT of 45 s or more, 22% had missing confirm ratios, and these values were imputed using multiple imputations.

    “Among those visits with DRVVT of 45 s or more, 22% had missing confirm ratios. These values were imputed using multiple imputations.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given
    § Discussion

    The main advantages of our study are a large number of patients with SLE, and the prospective assessment of both aPL and the thrombotic events.

    “The main advantages of our study are a large number of patients with SLE, and the prospective assessment of both aPL and the thrombotic events.”
    Quote in the paperSubstantial claim

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

    Premisecitation
    § Discussion

    For transiently positive antibodies, the strength of the association with thrombosis decreased for aCL and aPT, but remained the same for LA and anti-β2-glycoprotein I.

    “For transiently positive antibodies, the strength of the association with thrombosis decreased for aCL and aPT, but remained the same for LA and anti-β2-glycoprotein I.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [45] Male, 2005, Predictive value of persistent versus transient antiphospholipid antibody subtypes for the risk of thrombotic events in pediatric patients with systemic lupus erythematosus, Blood source

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

    Premisecitation
    § Discussion

    In a population-based case-control study, single LA positivity without anti-β2-glycoprotein I or anti-PT did not carry an increased risk for DVT.

    “In contrast, single LA positivity without anti-β2-glycoprotein I or anti-PT did not carry an increased risk for DVT [32].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] de Groot, 2005, Lupus anticoagulants and the risk of a first episode of deep venous thrombosis, J Thromb Haemost source

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

    Premisecitation
    § Discussion

    Male et al. found, in multivariate analyses, that LA was the strongest predictor of thrombosis, even if grouping patients with one or two positive tests.

    “Male et al. [45] found, in multivariate analyses, that LA was the strongest predictor of thrombosis, even if grouping patients with one or two positive tests.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] Male, 2005, Predictive value of persistent versus transient antiphospholipid antibody subtypes for the risk of thrombotic events in pediatric patients with systemic lupus erythematosus, Blood source

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

    Premisecitation
    § Discussion

    A Japanese group devised an antiphospholipid score (aPL-S) by testing multiple aPL, including three tests for LA (aPTT, kaolin clotting time and DRVVT) and six antiphospholipid assays (IgG and IgM aCL, IgG and IgM anti-β2-glycoprotein I, IgG and IgM aPS-PT) to diagnose APS and to predict the risk of thrombosis.

    “A Japanese group devised an antiphospholipid score (aPL-S) by testing multiple aPL, including three tests for LA (aPTT, kaolin clotting time and DRVVT) and six antiphospholipid assays (IgG and IgM aCL, IgG and IgM anti-β2-glycoprotein I, IgG and IgM aPS-PT) to diagnose APS and to predict the risk of thrombosis [35].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Otomo, 2012, Efficacy of the antiphospholipid score for the diagnosis of antiphospholipid syndrome and its predictive value for thrombotic events, Arthritis Rheum source

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

    Study design and conductown data
    § Discussion

    The number of thrombotic events in same categories was small.

    “A second limitation is that even given the large number of patients, the number of thrombotic events in same categories was small.”
    Quote in the paperNot a substantial claim

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

    Premisecitation
    § Discussion

    Some studies reported that the increased risk of thrombosis in SLE was associated with the presence of LA and with a persistently positive aCL.

    “Some studies reported that the increased risk of thrombosis in SLE was associated with the presence of LA and with a persistently positive aCL [41, 44].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [41] Martinez-Berriotxoa, 2007, Transiently positive anticardiolipin antibodies and risk of thrombosis in patients with systemic lupus erythematosus, Lupus source
    • cites [44] Tektonidou, 2009, Risk factors for thrombosis and primary thrombosis prevention in patients with systemic lupus erythematosus with or without antiphospholipid antibodies, Arthritis Rheum source

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

    Premisecitation
    § Discussion

    In a population-based case-control study, LA with the concomitant positivity of anti-β2-glycoprotein I or anti-PT showed the highest thrombosis risk.

    “In a population-based case–control study, LA with the concomitant positivity of anti-β2-glycoprotein I or anti-PT showed the highest thrombosis risk.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] de Groot, 2005, Lupus anticoagulants and the risk of a first episode of deep venous thrombosis, J Thromb Haemost source
36 of 36

  • The paper relies on this without support.

    Cross-sectional studies miss the true prevalence of aPL in SLE.

    “Cross-sectional studies miss the true prevalence of aPL in SLE.”

  • The paper relies on this without support.

    This is the first US SLE cohort study to examine categories of combinations of aPL and thrombosis risk.

    “This is the first US SLE cohort study to examine categories of combinations of aPL and thrombosis risk.”

  • The paper relies on this without support.

    The diagnostic and clinical significance of IgA isotype in SLE had been well demonstrated.

    “Although acceptance of the IgA isotype in APS remains controversial, its diagnostic and clinical significance in SLE had been well demonstrated.”

  • The paper relies on this without support.

    aPL thrombosis in SLE patients is thought to be greater with persistent aPL positivity.

    “aPL thrombosis in SLE patients is thought to be greater with persistent aPL positivity.”
4 of 4

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.

  • Significant added venous risk conflicts with the LA-positive analysis

    Major

    The paper describes a significant added venous thrombosis risk in patients who were also LA positive, but its analysis of that combination explicitly says the venous result was not statistically significant (P = 0.1081).

1 of 1

Cites

Flagged first, then by citations

3 of the 50 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Ruiz-Limon, 2012, IgA anti-β2glycoprotein I antibodies are pathogenetic in a mouse model of APS, Arthritis Rheum, 64, S742

Cited by

Sorted by citations

Related

Authors
Demir, S., Li, J., Magder, L. S., & Petri, M.
Affiliations
  • Johns Hopkins University (US)
  • University of Maryland, Baltimore (US)
Corresponding author
Petri, Michelle
ORCID
Venue
Rheumatology
Publisher
Oxford University Press (OUP)
Published
2020-12-17
Volume
60
Issue
8
Pages
3770-3777
ISSN
  • 1462-0324 (ISSN-L)
  • 1462-0332
DOI
10.1093/rheumatology/keaa857
PMC
PMC8328497
OpenAlex
W3115844088
Cited by
38
References
50
Citations by year
2026: 8 · 2025: 6 · 2024: 6 · 2023: 8 · 2022: 5 · 2021: 5
FWCI
2.88
Type
journal article
Language
en
Open access
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations
  • Lara D. Veeken (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
Funders
National Institutes of Health (AR 69572)
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
systemic lupus erythematosus, antiphospholipid antibodies, thrombosis risk, anticardiolipin antibodies, anti-beta2-glycoprotein I antibodies, lupus anticoagulant, arterial thrombosis, venous thrombosis
MeSH terms
Adult, Female, Humans, Immunoglobulin A, Immunoglobulin G, Immunoglobulin M, Ischemia, Lupus Erythematosus, Systemic

About these checks

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

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

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

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Statistics and arithmetic are recomputed, not judged.

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