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Cited by 5Systemic Lupus Erythematosus ResearchBlood Coagulation and Thrombosis MechanismsVenous Thromboembolism Diagnosis and Management

Lupus anticoagulant test persistence over time and its associations with future thrombotic events

Open access
Colling, Meaghan E., Ay, Cihan, Kraemmer, Daniel, Koder, Silvia, Quehenberger, Peter, Pabinger, Ingrid, Posch, Florian, Gebhart, Johanna·2022·Blood Advances
DOI 10.1182/bloodadvances.2021006011PMC PMC9131910
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Abstract

Data on lupus anticoagulant (LA) test stability in patients persistently positive for LA are limited, and its implications on clinical outcomes are lacking. We investigated the rate and predictors of a negative LA test and whether experiencing a negative test affected a patient’s risk of future thrombotic events or death in a prospective observational study of persistently LA+ patients. We followed 164 patients (84% women) for a median of 9.2 years and a total of 1438 follow-up visits. During the observation period, 50 thrombotic events (23 arterial and 27 venous events) occurred, and 24 patients died. Forty-six of the patients had at least 1 negative LA test during the observation period, corresponding to a 10-year cumulative incidence of a negative LA test of 28% (95% confidence interval, 20-35). The majority of patients with available follow-up after a negative LA test (n = 41) had at least 1 subsequent positive test for LA (n = 28/41, 68%). Vitamin K antagonist (VKA) treatment at baseline was associated with a negative LA test during follow-up. Using a multistate time-to-event model with multivariable adjustment, a negative LA test had no impact on a patient’s prospective risk of thrombosis or mortality. We conclude that a negative LA test during observation cannot be used clinically to stratify a patient’s risk for future events.

AI snapshot

Written from the paper’s full text.

TL;DR

In a prospective cohort of 164 patients persistently positive for lupus anticoagulant (LA), 28% had at least one negative LA test over a median follow-up of 9.2 years, but most who did later tested positive again. A negative LA test did not alter the prospective risk of arterial thrombosis, venous thrombosis, overall thrombosis, or death.

Key findings

  • 118/164 (72%) had stable LA positivity; 46 (28%) had ≥1 negative LA test, with a 10-year cumulative incidence of first negative LA test of 28% (95% CI 20-35). Among 41 with follow-up after first negative, 28 (68%) turned LA positive again; 10-year cumulative incidence of turning positive again was 64% (95% CI 48-77), median time 1.0 years (95% CI 0.8-2.5).
  • VKA treatment at baseline predicted a negative LA test: 10-year probability 21% without vs 37% with VKA (Gray’s test P = .034). After adjustment for VKA, prior thrombosis and aβ2GPI IgG positivity remained independently associated with ≥1 negative LA test, while higher aPTT-LA and higher antiprothrombin IgM/IgG predicted lower probability.
  • A negative LA test did not change prospective risk of ATE, VTE, total thrombosis, or mortality in univariable or multivariable multistate models (e.g., total thrombosis transition HR 0.86, 95% CI 0.36-2.08, P = .744 univariable; adjusted HR 1.14, 95% CI 0.45-2.93, P = .783). Landmark 10-year risks after 1.5 years for stable vs ≥1 negative LA were ATE 12% vs 0%, VTE 18% vs 17%, total thrombosis 31% vs 18%, death 12% vs 17%.

Methods

  • LATS is an ongoing single-center, biobank-based prospective observational cohort of adults repeatedly positive for LA (2 positive tests ≥6 or 12 weeks apart). This analysis included 164 of 215 enrolled patients after exclusions; 84% women, median age 41 years, 60% with prior thrombosis, 72% with established APS.
  • Patients returned every 6 months for the first 5 years and annually thereafter; 164 patients contributed 1438 follow-up visits (mean 9 visits/patient), with median follow-up for thrombosis 9.2 years. LA was assessed by PTT-LA and dRVVT screening with mixing/confirmatory tests; VKA patients used Rosner Index ≥15.
  • Analyses used Stata 15.1: competing-risk cumulative incidence, Gray’s/log-rank tests, Fine & Gray regression for LA status change, linear mixed-effects models for biomarkers, and unidirectional illness-death multistate models plus landmark analysis at 1.5 years for clinical outcomes.

Limitations

  • Stated: findings cannot be generalized to all APS or aPL-positive patients because only persistently LA-positive patients were included; LA testing could not always be done off VKA, making interpretation under anticoagulation controversial/challenging.
  • Stated: only the effect of the first negative LA test was analyzed; transiently vs persistently LA-negative patients were not compared because only 14/42 remained persistently negative.
  • Evident: single-center observational design, VKA exposure/confounding, and missing data for some biomarkers (e.g., aβ2GPI and antiprothrombin) limit causal inference and completeness; the text notes aβ2GPI was established after cohort inception.

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

Integrity signals

Registry

Crossref · 10.1182/bloodadvances.2021006011

Cites

42 of 42 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

9 of 25 cited sources checked · 5 supported · 0 flagged · accuracy not yet measured

  • Findingcitation

    The proportion of patients in the cohort who remained persistently LA+ (72%) was similar to rates in other studies that used different definitions of LA stability and positivity (78% in Gkrouzman et al, 71% in Zen et al, and 87% in Erkan et al).

    “However, the proportion of patients in our cohort who remained persistently LA+ (72%) was similar to the rates in other studies that used different definitions of LA stability and positivity (78% in the study by Gkrouzman et al, 71% in the study by Zen et al, and 87% in study by Erkan et al.).9,10,36”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites [9] Gkrouzman, 2021, Antiphospholipid antibody profile stability over time: prospective results from the APS ACTION clinical database and repository, J Rheumatol. 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 [10] Zen, 2021, Prevalence, outcome and management of patients with SLE and secondary antiphospholipid antibody syndrome after aPL seroconversion, Rheumatology (Oxford). source
    • cites [36] Erkan, 2005, Real world experience with antiphospholipid antibody tests: how stable are results over time?, Ann Rheum Dis. 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
  • Interpretationcitation

    The associations between antithrombotic treatment or thrombotic events and a negative LA test are consistent with the fact that LA testing is perturbed by anticoagulant treatment.

    “The associations between antithrombotic treatment or thrombotic events and a negative LA test are consistent with the fact that LA testing is perturbed by anticoagulant treatment.23,24”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [23] 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
    • cites [24] Depreter, 2017, Dilute Russell’s viper venom time reagents in lupus anticoagulant testing: a well-considered choice, Clin Chem Lab Med. source
  • Findingown data

    History of any thrombosis was a univariable predictor of increased probability of experiencing at least 1 negative LA test.

    “Additionally, history of any thrombosis, history of venous thrombosis, and presence and level of aβ2GPI IgG emerged as univariable predictors of an increased probability of experiencing at least 1 negative LA test (Table 2).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: There are no clearly defined criteria for LA positivity in patients on VKA treatment.
    • Rests on an assumption: It is not possible to interrupt VKA in patients with history of thrombosis just for study purposes.
  • Findingown data

    Among patients persistently positive for LA, 28% had at least one negative LA test during observation.

    “Twenty-eight percent of patients persistently positive for LA had a negative LA test during observation; most, subsequently, tested positive.”
    • Also stated in: § LA stability over time · plain
      “The other quarter of the study cohort (n = 46, 28%) had at least 1 negative LA test.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: There are no clearly defined criteria for LA positivity in patients on VKA treatment.
    • Rests on an assumption: It is not possible to interrupt VKA in patients with history of thrombosis just for study purposes.
  • Findingown data

    Median time to first subsequent positive LA test for those who turned LA negative was 1.0 years (95% CI 0.8-2.5).

    “Median time to a first subsequent positive LA test for those who turned LA negative was 1.0 years (95% CI, 0.8-2.5).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: There are no clearly defined criteria for LA positivity in patients on VKA treatment.
    • Rests on an assumption: It is not possible to interrupt VKA in patients with history of thrombosis just for study purposes.
  • Classified as probably not a substantial claim. 15
  • May combine two claims. 21

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    LA positivity was determined following SSC/ISTH recommendations at the time of testing.

    “LA positivity was determined following the Scientific and Standardization Committee (SSC)/International Society on Thrombosis and Hemostasis (ISTH) recommendations at the time of testing.11,13”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [11] Brandt, 1995, Criteria for the diagnosis of lupus anticoagulants: an update. On behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH, Thromb Haemost. source
    • cites [13] Pengo, 2009, Update of the guidelines for lupus anticoagulant detection, J Thromb Haemost. source

  • May combine two claims.

    Premisecitation

    Most prior efforts to risk-stratify patients for future thrombotic events have used aPL status from the first measurement or early in observation and have not analyzed changes over time.

    “Notably, most prior efforts to risk-stratify patients for future thrombotic events have used the patients’ aPL status from the first measurement or early in the observation period and have not analyzed changes over time.3,7,8”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [3] 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 [7] Reynaud, 2014, Risk of venous and arterial thrombosis according to type of antiphospholipid antibodies in adults without systemic lupus erythematosus: a systematic review and meta-analysis, Autoimmun Rev. source
    • cites [8] Danowski, 2009, Determinants of risk for venous and arterial thrombosis in primary antiphospholipid syndrome and in antiphospholipid syndrome with systemic lupus erythematosus, J Rheumatol. source

      The Methods (pp. 1–2) describe a cross-sectional assessment of aPL and thrombosis risk, with no analysis of changes in aPL status over time. This supports the paper as an example of a non-longitudinal effort, but it does not establish that most prior efforts used a first or early measurement; it also does not specify when this study’s aPL measurements occurred relative to observation. (LLM, conf=0.78)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Gkrouzman et al found that approximately 80% of their patients with clinically meaningful aPL at baseline had stable antibodies over time.

    “Recent work from Gkrouzman et al found that ∼80% of their patients with clinically meaningful aPL at baseline had stable antibodies, defined by a meaningful antibody profile in two-thirds of testing, over time.9”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [9] Gkrouzman, 2021, Antiphospholipid antibody profile stability over time: prospective results from the APS ACTION clinical database and repository, J Rheumatol. source

  • Classified as probably not a substantial claim.

    Premisecitation

    The presence of 1 or more aPL for 12 or more weeks constitutes the laboratory criteria for APS.

    “The presence of 1 or more of these aPL for 12 or more weeks constitutes the laboratory criteria for antiphospholipid syndrome (APS), an autoimmune disorder defined clinically by arterial and venous thrombotic events and/or pregnancy complications.5”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [5] Miyakis, 2006, International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS), J Thromb Haemost. source

      The revised laboratory criteria (Table 2) require at least one qualifying aPL test to be positive on two or more occasions at least 12 weeks apart. The citing sentence captures the persistence requirement but omits the repeat-testing requirement and the specified antibody types and titer thresholds; presence of any aPL alone does not suffice. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Little is known about the stability of aPL beyond 12 weeks, predictors of persistence, and whether subsequent fluctuations in antibody status affect future risk of thrombosis.

    “Although it is known that persistence, defined currently by 12 weeks, is associated with thrombotic risk, little is known about the stability of these antibodies beyond this time, predictors of persistence, and whether subsequent fluctuations in antibody status affect future risk of thrombosis.6”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [6] 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

    Interpretation of LA tests for patients on VKA remains controversial, and VKA use is associated with false negative and false positive LA results.

    “Interpretation of LA tests for patients on VKA remains controversial, and VKA use is associated with false negative and false positive LA results.25,26”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [25] Devreese, 2015, Mixing studies in lupus anticoagulant testing are required at least in some type of samples, J Thromb Haemost. source
    • cites [26] Aboud, 2010, False-negative or false-positive: laboratory diagnosis of lupus anticoagulant at the time of commencement of anticoagulant, J Thromb Haemost. source

  • Classified as probably not a substantial claim.

    Findingown data

    The analysis included 164 patients.

    “We included 164 patients in the analysis (Figure 1), the characteristics of whom are presented in Table 1.”
    Quote in the paperSubstantial claim

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

    Findingown data

    Among 46 patients who turned LA−, 5 did not have further follow-up.

    “Among those 46 patients who turned LA−, 5 patients did not have further follow-up, and 28 (68%) of the remaining 41 patients turned LA+ again, corresponding to a 10-year cumulative incidence of turning positive again of 64% (95% CI, 48-77, Figure 2B).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: There are no clearly defined criteria for LA positivity in patients on VKA treatment.
    • Rests on an assumption: It is not possible to interrupt VKA in patients with history of thrombosis just for study purposes.

  • May combine two claims.

    Findingown data

    During median follow-up for thrombosis of 9.2 years, 23 prospective ATEs, 27 prospective VTEs, and 24 patients died.

    “During a median follow-up for thrombosis of 9.2 years (with 75% and 25% of the cohort being followed-up for at least 4.0 and 14.9 years, respectively), we observed 23 prospective ATEs, 27 prospective VTEs, and 24 patients died.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In landmark analysis, the 10-year risk of ATE was 12% in patients with stable LA within the first 1.5 years of follow-up and 0% in those with at least 1 negative LA test during the first 1.5 years.

    “In landmark analysis, 10-year risks of ATE, VTE, total thrombosis, and death were 12%, 18%, 31%, and 12% in those patients with stable LA within the first 1.5 years of follow-up, and 0%, 17%, 18%, and 17% in those with at least 1 negative LA test during the first 1.5 year of follow-up, respectively (Figure 3).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In landmark analysis, the 10-year risk of VTE was 18% in patients with stable LA within the first 1.5 years of follow-up and 17% in those with at least 1 negative LA test during the first 1.5 years.

    “In landmark analysis, 10-year risks of ATE, VTE, total thrombosis, and death were 12%, 18%, 31%, and 12% in those patients with stable LA within the first 1.5 years of follow-up, and 0%, 17%, 18%, and 17% in those with at least 1 negative LA test during the first 1.5 year of follow-up, respectively (Figure 3).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In landmark analysis, the 10-year risk of death was 12% in patients with stable LA within the first 1.5 years of follow-up and 17% in those with at least 1 negative LA test during the first 1.5 years.

    “In landmark analysis, 10-year risks of ATE, VTE, total thrombosis, and death were 12%, 18%, 31%, and 12% in those patients with stable LA within the first 1.5 years of follow-up, and 0%, 17%, 18%, and 17% in those with at least 1 negative LA test during the first 1.5 year of follow-up, respectively (Figure 3).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Neither a negative LA test nor a simultaneous change in LA test and VKA status affected the levels of IgM or IgG isotype aCL or aβ2GPI, nor their subsequent trajectory over time.

    “Neither a negative LA test nor a simultaneous change in LA test and VKA status affected the levels of IgM or IgG isotype aCL or aβ2GPI, nor their subsequent trajectory over time (supplemental Tables 2 and 3).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In landmark analysis, the 10-year risk of total thrombosis was 31% in patients with stable LA within the first 1.5 years of follow-up and 18% in those with at least 1 negative LA test during the first 1.5 years.

    “In landmark analysis, 10-year risks of ATE, VTE, total thrombosis, and death were 12%, 18%, 31%, and 12% in those patients with stable LA within the first 1.5 years of follow-up, and 0%, 17%, 18%, and 17% in those with at least 1 negative LA test during the first 1.5 year of follow-up, respectively (Figure 3).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    After controlling for initial VKA use, a longer aPTT-LA and higher titer IgM or IgG antiprothrombin antibodies at baseline predicted LA stability.

    “Conversely, after controlling for initial VKA use, a longer aPTT-LA and higher titer IgM or IgG antiprothrombin antibodies at baseline predicted LA stability.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the multivariable analysis, neither the presence of aCL nor triple positivity predicted LA test results over time.

    “In our multivariable analysis, neither the presence of aCL nor triple positivity predicted LA test results over time.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Using an alternative definition of LA positivity based only on the LA test and the Rosner Index and applied regardless of VKA status, 63 patients (38%) developed at least 1 negative LA test during follow-up, corresponding to a 10-year cumulative incidence of 39% (95% CI, 31-47).

    “Using an alternative definition of LA positivity that is only based on the LA test and the Rosner Index and applied to patients regardless of VKA status (described in supplemental Paragraph 1), we found that n = 63 patients (38%) developed at least 1 negative LA test during follow-up, corresponding to a 10-year cumulative incidence of 39% (95% CI, 31-47).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The levels of aCL IgM, aCL IgG, aβ2GPI IgM, and aβ2GPI IgG decreased over time.

    “The levels of these antibodies decreased over time.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Most patients had just a transiently negative LA test, as 68% of those who had a negative test result and had follow-up turned positive again.

    “Most patients had just a transiently negative LA test as 68% of those who had a negative test result and had followed up turned positive again.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Average aPTT-LA at baseline was 91 seconds and declined by 1.1 seconds per year.

    “The average aPTT-LA at baseline was 91 seconds and declined by 1.1 seconds per year (supplemental Table 1).”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    Missing data for key variables was minimal except for aβ2GPI.

    “Overall, missing data for key variables was minimal except for aβ2GPI (as this parameter was established after the inception of the cohort, supplemental Figure 1).”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    The association between LA and thrombosis, both arterial and venous, was described in the 1960s.

    “The association between lupus anticoagulant (LA), the first aPL identified, and thrombosis, both arterial and venous, was described in the 1960s.1”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Bowie, 1963, Thrombosis in systemic lupus erythematosus despite circulating anticoagulants, J Lab Clin Med.

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

    Study design and conductnone given

    Thrombotic events were verified with appropriate diagnostic imaging tests and evaluated by an adjudication committee of designated experts.

    “Thrombotic events were verified with appropriate diagnostic imaging tests and evaluated by an adjudication committee of designated experts in the field.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Additional antibodies, most notably aCL and aβ2GPI, were later identified and associated with thrombosis and recurrent spontaneous abortions.

    “Additional antibodies, most notably anticardiolipin antibodies (aCL) and anti–glycoprotein-I antibodies (aβ2GPI), were later identified and associated with thrombosis and recurrent spontaneous abortions.2-4”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [2] McNeil, 1991, Immunology and clinical importance of antiphospholipid antibodies, Adv Immunol. source
    • cites [3] 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 [4] Opatrny, 2006, Association between antiphospholipid antibodies and recurrent fetal loss in women without autoimmune disease: a metaanalysis, J Rheumatol.

      Not checked in the free run.

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

    Premisecitation

    In that study, treatment with immunosuppression was predictive of development of seronegativity.

    “Treatment with immunosuppression was predictive of development of seronegativity, whereas triple positivity and diagnosis of APS prior to SLE were predictive of aPL stability over time.10”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Zen, 2021, Prevalence, outcome and management of patients with SLE and secondary antiphospholipid antibody syndrome after aPL seroconversion, Rheumatology (Oxford). source

  • May combine two claims.

    Premisereasoning

    Limited prospective data on variability of aPL over time and no data on clinical implications of this variability are available.

    “Overall, limited prospective data on the variability of aPL over time and no data on the clinical implications of this variability, specifically if it is predictive of future thrombotic events or mortality, are available”
    Quote in the paperSubstantial claim

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

    Premisecitation

    In that study, triple positivity and diagnosis of APS prior to SLE were predictive of aPL stability over time.

    “Treatment with immunosuppression was predictive of development of seronegativity, whereas triple positivity and diagnosis of APS prior to SLE were predictive of aPL stability over time.10”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Zen, 2021, Prevalence, outcome and management of patients with SLE and secondary antiphospholipid antibody syndrome after aPL seroconversion, Rheumatology (Oxford). source

  • May combine two claims.

    Study design and conductown data

    The study did not compare patients who became transiently LA negative to patients who became persistently negative, as the number of persistently negative patients was very low (only 14/42 patients remained persistently negative).

    “We did not compare patients who became transiently LA negative to patients who became persistently negative, as the number of those latter patients was very low (only 14/42 patients remained persistently negative).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Transient consumption of antiphospholipid antibodies during and after a thrombotic event is unlikely to explain the findings, because only 37% (17/46) of patients who experienced a negative test had a thrombotic event during observation.

    “However, this is unlikely to explain our findings as only 37% (17/46) of the patients that experienced a negative test had a thrombotic event during observation.”
    Quote in the paperNot a substantial claim

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

    Study design and conductreasoning

    Because of the regularity in which patients underwent antibody testing, the study was unable to complete all testing for LA while patients were off VKA.

    “Second, given the regularity in which patients underwent antibody testing, we were unable to complete all testing for LA while patients were off VKA.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The study only analyzed the effect of the first negative test on future events.

    “Finally, we only analyzed the effect of the first negative test on future events.”
    Quote in the paperSubstantial claim
31 of 31

  • The paper relies on this without support.

    There are no clearly defined criteria for LA positivity in patients on VKA treatment.

    “As there are no clearly defined criteria for LA positivity in patients on VKA treatment, and as it is not possible to interrupt VKA in patients with history of thrombosis just for study purposes, we used the Rosner Index in addition to the predefined LA criteria.14”

  • The paper relies on this without support.

    It is not possible to interrupt VKA in patients with history of thrombosis just for study purposes.

    “As there are no clearly defined criteria for LA positivity in patients on VKA treatment, and as it is not possible to interrupt VKA in patients with history of thrombosis just for study purposes, we used the Rosner Index in addition to the predefined LA criteria.14”

  • The authors state this as an assumption.

    Patients on VKA had a higher baseline risk of thrombosis because they were more likely to have a history of thrombosis compared with patients on no anticoagulation.

    “We assume that our patients on VKA had a higher baseline risk of thrombosis given they were more likely to have a history of thrombosis compared with patients on no anticoagulation.”
3 of 3

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.

  • Hazard ratio falls outside its reported confidence interval

    Minor

    The adjusted antiprothrombin IgM hazard ratio is 0.75, below the lower bound of its reported 95% confidence interval, 0.79.

  • Conflicting counts of patients followed after a negative LA test

    Minor

    The results state that 41 patients had follow-up after their first negative LA test, but the Figure 2 caption says that analysis included 42 such patients.

  • Pregnancy-complication row reports no missing data despite a smaller denominator

    Minor

    The table reports pregnancy-complication data for 102 patients with 0% missing, while its note identifies 117 women with a documented pregnancy as the subgroup for this measure. That leaves 15 subgroup members unaccounted for.

3 of 3

Cites

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Authors
Colling, M. E., Ay, C., Kraemmer, D., Koder, S., Quehenberger, P., Pabinger, I., Posch, F., & Gebhart, J.
Affiliations
  • National Institutes of Health (US)
  • Medical University of Vienna (AT)
  • Medical University of Graz (AT)
ORCID
Venue
Blood Advances
Publisher
American Society of Hematology
Published
2022-05-13
Volume
6
Issue
10
Pages
2957-2966
ISSN
  • 2473-9529 (ISSN-L)
  • 2473-9537
DOI
10.1182/bloodadvances.2021006011
PMC
PMC9131910
OpenAlex
W4205774575
Cited by
5
References
42
Citations by year
2026: 1 · 2024: 4
FWCI
0.62
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Blood Advances (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
Topics
  • Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
  • Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
Keywords
lupus anticoagulant, thrombosis risk, venous thromboembolism, arterial thrombosis, mortality, vitamin K antagonists, anticoagulation, antiphospholipid syndrome
MeSH terms
Anticoagulants, Blood Coagulation Tests, Female, Humans, Male, Prospective Studies, Thrombosis, Lupus Coagulation Inhibitor

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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.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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