CoChat
Sign Up
Cited by 465Systemic Lupus Erythematosus ResearchVenous Thromboembolism Diagnosis and ManagementBlood Coagulation and Thrombosis Mechanisms

Incidence of a first thromboembolic event in asymptomatic carriers of high-risk antiphospholipid antibody profile: a multicenter prospective study

Open access
Pengo, Vittorio, Ruffatti, Amelia, Legnani, Cristina, Testa, Sophie, Fierro, Tiziana, Marongiu, Francesco, De Micheli, Valeria, Gresele, Paolo +7 more·2011·Blood
DOI 10.1182/blood-2011-03-340232
Open this paper in CoChat — free accountOpen PDF

Abstract

Persistent antiphospholipid (aPL) antibodies are occasionally found in subjects without prior history of thromboembolic events (TEs), raising the dilemma of whether to initiate or not a primary thromboprophylaxis. A first TE is considered rare in aPL carriers, but previous studies did not consider the aPL profile nor was the test positivity confirmed in a reference laboratory. In this study, 104 subjects with high-risk aPL profile (positive lupus anticoagulant, anticardiolipin, and anti-β2–glycoprotein I antibodies, triple positivity) confirmed in a reference laboratory, were followed up for a mean of 4.5 years. There were 25 first TEs (5.3% per year): the cumulative incidence after 10 years was 37.1% (95% confidence interval [CI], 19.9%-54.3%). On multivariate analysis, male sex (hazard ratio = 4.4; 95% CI, 1.5-13.1, P = .007) and risk factors for venous thromboembolism (hazard ratio = 3.3; 95% CI, 1.3-8.5, P = .01) were independent predictors for TEs. Aspirin did not significantly affect the incidence of TE. In conclusion, the occurrence of a first TE in carriers of high-risk aPL profile is considerable; it is more frequent among male subjects and in the presence of additional risk factors for venous TE. These data can help in the decision to initiate primary thromboprophylaxis in these subjects.

AI snapshot

Written from the paper’s full text.

TL;DR

In 104 asymptomatic carriers of triple-positive antiphospholipid antibodies confirmed in a reference laboratory, first thromboembolic events occurred at 5.3% per year, with a 10-year cumulative incidence of 37.1%. Male sex and venous thromboembolism risk factors independently predicted events, whereas aspirin did not significantly reduce them.

Key findings

  • During 469 patient-years of follow-up, there were 25 first thromboembolic events (5.3% per year); cumulative incidence was 9.8% (95% CI, 3.7%-15.9%) at 2 years, 27.3% (95% CI, 17.1%-37.5%) at 5 years, and 37.1% (95% CI, 19.9%-54.3%) at 10 years.
  • On multivariate analysis, independent predictors of thromboembolism were male sex (hazard ratio 4.4; 95% CI, 1.5-13.1; P = .007) and presence of risk factors for venous thromboembolism (hazard ratio 3.3; 95% CI, 1.3-8.5; P = .01).
  • Aspirin prophylaxis did not significantly affect thromboembolic events on multivariate analysis (hazard ratio 0.5; 95% CI, 0.2-1.5; P = .2); it was close to significance on univariate analysis but did not achieve statistical significance.
  • Among the 25 events, there were 12 arterial and 11 venous thromboembolic events, 1 right atrial thrombosis, and 1 renal thrombotic microangiopathy.

Methods

  • Multicenter prospective cohort of 104 subjects with high-risk antiphospholipid antibody profile (triple positivity: lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein I antibodies) on 2 occasions at least 12 weeks apart, without clinical features of antiphospholipid syndrome; triple positivity was confirmed in a reference laboratory. Mean age was 45 years, 79% were female, and mean follow-up was 4.5 years.
  • Subjects were seen annually or earlier as clinically indicated; no long-term anticoagulant treatment was prescribed, and short-term low-molecular-weight heparin was given in high-risk thromboembolism scenarios. Data collected included demographic, laboratory, and clinical variables, autoimmune disease, arterial and venous risk factors, and aspirin treatment.
  • Kaplan-Meier survival analysis estimated cumulative incidence of thromboembolism; Cox regression survival analysis identified predictors among demographic factors, autoimmune diseases, anticardiolipin isotype, arterial and venous risk factors, and aspirin treatment. Statistical significance was set at P < .05; analyses used SPSS.

Limitations

  • The paper does not include a formal limitations section. It states that larger clinical trials are definitely needed to test hypotheses about aspirin and hydroxychloroquine.
  • Evident from the text: treatment with aspirin was observational rather than randomized, so confounding by indication cannot be excluded; the cohort had 104 subjects and 25 events, yielding wide confidence intervals for some estimates.

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

Integrity signals

Registry

Crossref · 10.1182/blood-2011-03-340232

Cites

28 of 28 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

4 of 15 cited sources checked · 1 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Single antiphospholipid-positive carriers have an annual event rate of 1.36%.

    “that (1.36%) of 125 single aPL positive carriers with a mean age of 41 years (data taken by a recently published study by our group), 15”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [15] Ruffatti, 2011, Risk factors for a first thrombotic event in antiphospholipid antibody carriers: a prospective multicentre follow-up study., Ann Rheum Dis source

      The Results and Discussion report an annual thrombosis incidence of 1.86 per 100 patients for the full cohort of 258 aPL carriers. Searches for 125 single-positive carriers and a 1.36% annual rate found no passage reporting that subgroup rate; the overall rate does not establish or contradict it. (LLM, conf=0.73)

      Experimental — accuracy not yet measured
  • Interpretationreasoning

    The higher incidence of thromboembolic events observed in this study may be attributable to the selection of a high-risk antiphospholipid-positive population.

    “the higher incidence of TEs recorded in this study may be related to the selection of high-risk aPL-positive population”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [15] Ruffatti, 2011, Risk factors for a first thrombotic event in antiphospholipid antibody carriers: a prospective multicentre follow-up study., Ann Rheum Dis source

      The Analysis of risk factors for thrombosis identifies hypertension and lupus anticoagulant as independent predictors of thrombotic events, supporting the premise that risk profile matters. The Discussion describes this source paper’s own event rate as low and similar to other studies; it does not assess whether selection of a high-risk population explains the higher incidence in the citing study. Page numbers were not available in our copy. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
    • cites [16] Mok, 2005, Incidence and risk factors of thromboembolism systemic lupus erythematosus: a comparison of three ethnic groups., Arthritis Rheum source
  • Findingown data

    Of the 18 patients given hydroxychloroquine, 2 (11%) experienced a first thromboembolic event during follow-up.

    “Of the 18 patients treated with hydroxychloroquine, 2 (11%) had a first TE in the follow-up period.”
    Quote in the paperSubstantial claim
  • Findingown data

    The presence of risk factors predisposing to venous thromboembolism was an independent predictor of a first thromboembolic event in this cohort (multivariate hazard ratio 3.3; 95% CI, 1.3-8.5; P = .01).

    “male sex (hazard ratio ϭ 4.4; 95% CI, 1.5-13.1,P ϭ .007)and the presence of factors predisposing to VTE (hazard ratio ϭ 3.3; 95% CI, 1.3-8.5,P ϭ .01)were found to be independent predictors for clinical events”
    Quote in the paperSubstantial claim
  • Findingown data

    Aspirin prophylaxis did not significantly reduce thromboembolic events in this cohort on multivariate analysis (hazard ratio 0.5; 95% CI, 0.2-1.5; P = .2).

    “Aspirin prophylaxis was close to significance in reducing events on univariate analysis but did not achieve statistical significance on multivariate analysis (hazard ratio ϭ 0.5; 95% CI, 0.2-1.5,P ϭ .2)”
    • Also stated in: § Abstract · plain
      “As-pirin did not significantly affect the incidence of TE.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 7
  • May combine two claims. 3

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

    Premisecitation

    The annual rate of a first cardiovascular event, including venous thromboembolism, in the normal white population aged 35 to 55 years is about 0.4%.

    “the annual rate (ϳ 0.4%) of first cardiovascular event (including VTE) in normal white population at 35 to 55 years of age, 14”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [14] Roger, 2011, Heart disease and stroke statistics: 2011 update. A report from the American Heart Association., Circulation source

      The Cardiovascular Diseases > Incidence section reports 3 first cardiovascular events per 1,000 men annually at ages 35–44, which is close to the claimed 0.4%. It does not give a single rate for a healthy white population aged 35–55. The Venous Thromboembolism > Incidence section reports VTE separately, not as part of that first-event rate; page numbers were not supplied. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Triple positivity on all three antiphospholipid tests is associated with thrombosis and identifies high-risk patients with antiphospholipid syndrome.

    “triple positivity (all 3 tests positive) is associated with thrombosis and identifies high-risk patients with aPL syndrome (APS).6,7”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [6] Pengo, 2005, Antibody profiles for the diagnosis of antiphospholipid syndrome., Thromb Haemost source
    • cites [7] Pengo, 2009, Clinical course of high risk patients diagnosed with antiphospholipid syndrome (APS)., J Thromb Haemost source

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Thromboembolic events during follow-up were objectively diagnosed using predefined imaging or laboratory criteria, such as compression ultrasonography or venography for deep vein thrombosis and spiral tomography, ventilation-perfusion scanning, or pulmonary angiography for pulmonary embolism.

    “Venous thromboembolism (VTE) was diagnosed by compression ultrasonography or venography in case of deep vein thrombosis, and spiral tomography, ventilation-perfusion lung scan, or pulmonary angiography in case of pulmonary embolism.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationown data

    These data can assist the decision whether to start primary thromboprophylaxis in carriers of a high-risk antiphospholipid antibody profile.

    “These data can help in the decision to initiate primary thromboprophylaxis in these subjects.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The clinical course of persons carrying a high-risk antiphospholipid antibody profile (triple positivity) is not known.

  • May combine two claims.

    Interpretationown data

    First thromboembolic events are more frequent among male carriers and among those with additional venous thromboembolism risk factors.

    “it is more frequent among male subjects and in the presence of additional risk factors for venous TE”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Male sex is related to a higher risk of recurrent venous thromboembolism among patients with unprovoked deep vein thrombosis.

    “That male sex is related to a higher risk for recurrence of VTE among patients with unprovoked deep vein thrombosis is not new.25”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] McRae, 2006, Effect of patient's sex on risk of recurrent venous thromboembolism: a meta-analysis., Lancet source

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

    Study design and conductnone given

    The study was approved by the local ethics committee of each participating Thrombosis Center.

    “The study was approved by the local ethics committee of each Thrombosis Center.”
    Quote in the paperNot a substantial claim

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

    Study design and conductown data

    Triple positivity for antiphospholipid antibodies was confirmed by retesting plasma from each center in a reference laboratory, and inclusion required confirmation of LA positivity together with aCL and anti-β2GPI positivity above the 99th percentile of 40 healthy subjects for the same isotype.

    “plasma from patients of each center was retested in a reference laboratory (Padua Thrombosis Center).Final inclusion in the cohort required confirmation of LA positivity as well as aCL and anti-␤ 2 GPI antibody positivity (values in the upper 99th percentile of 40 healthy subjects) for the same isotype.”
    Quote in the paperSubstantial claim
8 of 8

  • The paper relies on this without support.

    The clinical course of persons carrying a high-risk antiphospholipid antibody profile (triple positivity) is not known.

    “The clinical course in persons with high-risk aPL antibody profile (triple positivity) is not known, casting a shadow on the need for primary prophylaxis to avoid TEs.”
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 [8]

    Table 3 (Discussion; page unavailable) compares anticardiolipin antibody titres in participants with and without thrombosis and reports a univariate hazard ratio of 1.0 (95% CI, 0.99–1.01). In this cohort, the paper does not find the claimed association between higher titres and higher thromboembolic risk; it identifies male sex and venous risk factors as independent predictors instead. (LLM, conf=0.84)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • Triple-positive patients have a high risk for developing a first thrombotic event and recurrence of thrombosis.

    “Patients positive for the combination of LAC, antiβ 2GPI, and anti-CL antibodies,theso-called triple-positive patients, exhibit a high risk for developing a first thrombotic event and recurrence of thrombosis. 8,9”

    From Clinical Relevance of Isolated Lupus Anticoagulant Positivity in Patients with Thrombotic Antiphospholipid Syndrome (2021) · cites this paper as [9]

    The Results report a considerable risk of a first thromboembolic event among 104 triple-positive carriers (25 events; 5.3% per year). The study followed people without prior thromboembolic events, so it does not establish the claimed risk of thrombosis recurrence. Page numbers are unavailable in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Patients positive for all three aPLs are identified as individuals at high risk for a first clinical event and for recurrence.

    “andpatientspositiveforallthree aPLs are identified as individuals at high risk for a first clinical event and for recurrence. 8,9”

    From Clinical Relevance of Isolated Lupus Anticoagulant Positivity in Patients with Thrombotic Antiphospholipid Syndrome (2021) · cites this paper as [9]

    The Results (page not available in our copy) report 25 first thromboembolic events among 104 triple-positive carriers, supporting the claim about a first clinical event. The study followed people without prior clinical APS events and did not establish their risk of recurrence; its Introduction calls triple-positive patients with APS high-risk but does not quantify recurrence risk. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Most triple-positivity studies report LA testing as positive without distinguishing between dRVVT and APTT and single-assay positivity or only perform dRVVT.

    “Of note is that many studies on triple positivity merely report patients as being positive for LA without assessing dRVVT and APTT results separately [10,[23][24][25][26][27][28][29], or even use only 1 assay [7,8,12].”

    From Triple-positive antiphospholipid syndrome does not guarantee positivity in each lupus anticoagulant assay (2023) · cites this paper as [8]

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

    “it has been demonstrated that asymptomatic persistent carriers of LA and of the other antiphospholipid antibodies have a higher risk of future thromboembolic events [11,12].”

    From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [11]

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.

  • IgM anticardiolipin units conflict

    Minor

    The methods specify MPL units for IgM anticardiolipin values, but Table 1 labels the IgM anticardiolipin values as GPL units.

1 of 1

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Pengo, V., Ruffatti, A., Legnani, C., Testa, S., Fierro, T., Marongiu, F., De Micheli, V., Gresele, P., Tonello, M., Ghirarduzzi, A., Bison, E., Denas, G., Banzato, A., Padayattil Jose, S., & Iliceto, S.
Affiliations
  • Departments of Clinical Cardiology and
  • University of Padua (IT)
  • University of Bologna (IT)
  • District Hospital, Cremona, Italy;
  • University of Perugia (IT)
  • University of Cagliari (IT)
  • Transfusion Medicine, District Hospital, Merate, Italy; and
  • Santa Maria Nuova Hospital (IT)
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
2011-10-27
Volume
118
Issue
17
Pages
4714-4718
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood-2011-03-340232
OpenAlex
W1975074770
Cited by
465
References
28
Citations by year
2026: 11 · 2025: 14 · 2024: 33 · 2023: 36 · 2022: 19 · 2021: 40 · 2020: 46 · 2019: 41 · 2018: 39 · 2017: 38 · 2016: 29 · 2015: 23 · 2014: 32 · 2013: 28 · 2012: 28
FWCI
19.25
Type
journal article
Language
en
Open access
Licence
other-oa
Locations
  • Blood (publishedVersion)
  • PubMed (publishedVersion)
  • UNICA IRIS Institutional Research Information System (University of Cagliari) (submittedVersion, other-oa)
  • Padua Research Archive (University of Padova) (submittedVersion)
Topics
  • Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
  • Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
Keywords
antiphospholipid antibodies, thromboembolic events, lupus anticoagulant, anticardiolipin antibodies, anti-beta2-glycoprotein I antibodies, triple positivity, venous thromboembolism, aspirin
MeSH terms
Adolescent, Adult, Aged, Disease Susceptibility, Female, Follow-Up Studies, Humans

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.

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 ›

Are you an author, or do you see a problem with this page? Request a review