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Cited by 184Systemic Lupus Erythematosus ResearchBlood Coagulation and Thrombosis MechanismsVenous Thromboembolism Diagnosis and Management

Risk factors for a first thrombotic event in antiphospholipid antibody carriers: a prospective multicentre follow-up study.

Open access
Ruffatti, Amelia, Del Ross, Teresa, Ciprian, Manuela, Bertero, Maria T, Salvatore, Sciascia, Scarpato, Salvatore, Montecucco, Carlomaurizio, Rossi, Silvia +12 more·2011·Annals of the Rheumatic Diseases
DOI 10.1136/ard.2010.142042
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Abstract

Objectives To assess risk factors for a first thrombotic event in confirmed antiphospholipid (aPL) antibody carriers and to evaluate the efficacy of prophylactic treatments.Methods Inclusion criteria were age 18-65 years, no history of thrombosis and two consecutive positive aPL results. Demographic, laboratory and clinical parameters were collected at enrolment, once a year during the follow-up and at the time of the thrombotic event, whenever that occurred.Results 258 subjects were prospectively observed between October 2004 and October 2008. The mean ± SD follow-up was 35.0 ± 11.9 months (range 1-48). A first thrombotic event (9 venous, 4 arterial and 1 transient ischaemic attack) occurred in 14 subjects (5.4%, annual incidence rate 1.86%). Hypertension and lupus anticoagulant (LA) were significantly predictive of thrombosis (both at p<0.05) and thromboprophylaxis was significantly protective during high-risk periods (p<0.05) according to univariate analysis. Hypertension and LA were identified by multivariate logistic regression analysis as independent risk factors for thrombosis (HR 3.8, 95% CI 1.3 to 11.1, p<0.05, and HR 3.9, 95% CI 1.1 to 14, p<0.05, respectively).Conclusions Hypertension and LA are independent risk factors for thrombosis in aPL carriers. Thromboprophylaxis in these subjects should probably be limited to high-risk situations.

AI snapshot

Written from the paper’s full text.

TL;DR

In 258 confirmed antiphospholipid antibody carriers without prior thrombosis, hypertension and lupus anticoagulant were independent risk factors for a first thrombotic event. Thromboprophylaxis appeared protective only when given during high-risk periods.

Key findings

  • A first thrombotic event occurred in 14/258 subjects (5.4%; annual incidence rate 1.86 per 100 patients per year): 9 venous thromboses, 4 arterial thromboses, and 1 transient ischaemic attack.
  • Multivariate Cox analysis identified hypertension (HR 3.8, 95% CI 1.3 to 11.1, p<0.05) and lupus anticoagulant (HR 3.9, 95% CI 1.1 to 14, p<0.05) as independent risk factors for thrombosis.
  • Univariate analysis found hypertension and lupus anticoagulant significantly associated with thrombosis (both p<0.05); Kaplan-Meier analysis showed higher cumulative incidence with hypertension (p<0.01) and lupus anticoagulant (p<0.05).
  • Thromboprophylaxis during high-risk periods was significantly protective (OR 0.1, 95% CI 0.01 to 0.9, p<0.05), whereas continuous prophylaxis was not associated with reduced thromboembolic events.

Methods

  • Prospective multicentre follow-up study of 258 Caucasian confirmed aPL carriers (223 women, 35 men; mean±SD age 40.9±11.1 years) aged 18–65 with no history of thrombosis and at least two consecutive positive aPL results no less than 12 weeks apart, recruited from 11 Italian rheumatology centres between 15 October 2004 and 15 October 2008.
  • Mean±SD follow-up was 35.0±11.9 months; clinical and laboratory parameters were collected at enrolment, once a year, and at any thrombotic event; aPL testing included lupus anticoagulant, IgG/IgM anticardiolipin, and IgG/IgM anti-β2-glycoprotein I.
  • Analyses included univariate tests, Kaplan-Meier survival analysis with log-rank tests, McNemar test, and multivariate Cox proportional hazards modelling adjusted for age, sex, aPL antibodies, hypertension, autoimmune diseases, pregnancy/puerperium, smoking, hypercholesterolaemia, body mass index, pill/hormone replacement therapy, and diabetes mellitus.

Limitations

  • The paper states that there was no central laboratory for aPL testing and that the follow-up period was short.
  • Evident from the text: only 14 thrombotic events occurred, limiting statistical power and precision.
  • Evident from the text: prophylaxis was not randomized, long-term low-dose aspirin was initiated arbitrarily for specified reasons, and drug compliance was monitored by self-report, so confounding by indication is possible.

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

Integrity signals

Registry

Crossref · 10.1136/ard.2010.142042

Cites

24 of 24 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

3 of 19 cited sources checked · 1 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    Retrospective, case-control and cross-sectional studies with different designs, patient selection criteria, aPL profiles and risk factors have produced contradictory results.

    “Retrospective, [1][2][3][4] case-control [5][6][7][8][9][10][11][12] and cross-sectional 13,14 studies with different designs, patient selection criteria, aPL profiles and risk factors have produced contradictory results.”
    Quote in the paperSubstantial claim3 of 10 sources checked
    • cites [1] Silver, 1994, Clinical consequences of antiphospholipid antibodies: an historic cohort study., Obstet Gynecol
    • cites [2] Shah, 1998, Outcome of patients with anticardiolipin antibodies: a 10 year follow-up of 52 patients., Lupus source
    • cites [3] Erkan, 2001, High thrombosis rate after fetal loss in antiphospholipid syndrome: effective prophylaxis with aspirin., Arthritis Rheum source
    • cites [4] Janardhan, 2004, Anticardiolipin antibodies and risk of ischemic stroke and transient ischemic attack: the Framingham cohort and offspring study., Stroke source

      The cited paper is not a retrospective, case-control, or cross-sectional study of the kind listed in the citing sentence. Its Subjects and Definition of Clinical Outcome section says participants were followed for 11 years to identify incident stroke or TIA, and its Discussion explicitly calls the design a prospective population-based cohort study. The paper does acknowledge conflicting earlier findings, but its classification in this list is contrary to our copy. (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
    • cites [5] de Groot, 2005, Lupus anticoagulants and the risk of a first episode of deep venous thrombosis., J Thromb Haemost source
    • cites [6] Saidi, 2009, Lupus anticoagulants and anti-phospholipid antibodies as risk factors for a first episode of ischemic stroke., J Thromb Haemost source
    • cites [7] Ginsburg, 1992, Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis., Ann Intern Med source
    • cites [8] Vaarala, 1995, Anti-cardiolipin antibodies and risk of myocardial infarction in a prospective cohort of middle-aged men., Circulation source
    • cites [9] Runchey, 2002, Anticardiolipin antibodies as a risk factor for venous thromboembolism in a population-based prospective study., Br J Haematol source
    • cites [10] Naess, 2006, A prospective study of anticardiolipin antibodies as a risk factor for venous thrombosis in a general population (the HUNT study)., J Thromb Haemost source

      The Introduction (page unavailable) reports differing findings across prior studies, and the Discussion (page unavailable) contrasts the HUNT results with other studies while identifying differences in design, participant selection and antibody assays. Our copy does not establish the sentence’s specific claim about cross-sectional studies or show that differing risk factors account for the contradictory results. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
  • Findingown data

    No serious adverse events such as major bleeding episodes occurred during prophylaxis in the study participants.

    “Although none of the participants developed serious adverse events such as major bleeding episodes during prophylaxis, three patients discontinued long-term prophylaxis for personal reasons.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Antithrombotic prophylaxis administered during high-risk situations is significantly protective against thromboembolic events in antiphospholipid antibody carriers (OR 0.1, 95% CI 0.01 to 0.9, p<0.05).

    “Thromboembolic events were significantly reduced only when antithrombotic prophylaxis was administered in high-risk situations (OR 0.1, 95% CI 0.01 to 0.9, p<0.05).”
    • Also stated in: § Discussion · plain
      “Primary prophylaxis in high-risk situations was found to be a significant protective factor against thrombosis according to univariate analysis.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Drug compliance self-reports accurately reflect actual compliance.
    • Rests on an assumption: The association between high-risk prophylaxis and reduced thrombosis is not due to confounding by indication or other unmeasured confounders.
  • Findingown data

    Lupus anticoagulant positivity is significantly associated with thrombosis in antiphospholipid antibody carriers according to univariate analysis.

    “Hypertension and LA were significantly associated with thrombosis (both p<0.05).”
    • Also stated in: § Analysis of risk factors for thrombosis · plain
      “As shown in figure 1, Kaplan-Meier survival analysis provided similar results: the cumulative incidence of thromboembolic events was significantly higher in patients with hypertension (p<0.01) and LA (p<0.05).”
    Quote in the paperSubstantial claim
  • Findingown data

    Lupus anticoagulant positivity is an independent risk factor for thrombosis in confirmed antiphospholipid antibody carriers without a history of thrombosis (HR 3.9, 95% CI 1.1 to 14, p<0.05).

    “Hypertension and LA were identified by multivariate logistic regression analysis as independent risk factors for thrombosis (HR 3.8, 95% CI 1.3 to 11.1, p<0.05, and HR 3.9, 95% CI 1.1 to 14, p<0.05, respectively).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The study cohort is representative of confirmed antiphospholipid antibody carriers without a history of thrombosis.
  • Classified as probably not a substantial claim. 2
  • May combine two claims. 3

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

    Study design and conductnone given

    The absence of a central laboratory for antiphospholipid antibody testing is a limitation of the study.

    “The fact that there was no central laboratory for aPL testing, which certainly represents a missed opportunity, and the short follow-up period can be considered limitations of the study.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    The short follow-up period is a limitation of the study.

    “The fact that there was no central laboratory for aPL testing, which certainly represents a missed opportunity, and the short follow-up period can be considered limitations of the study.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The number of thrombotic events in this study was similar to that reported in other studies and in the authors' own retrospective study.

    “Finally, the number of thrombotic events was rather low (incidence rate 1.86% per 100 patients per year) and similar to that reported in other studies [1][2][3]7,8,13,16 and by our own retrospective study.15”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [1][2][3]7,8,13,16

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

    • cites [15] Ruffatti, 2009, Risk factors for a first thrombotic event in antiphospholipid antibody carriers. A multicentre, retrospective follow-up study., Ann Rheum Dis source

  • May combine two claims.

    Premisecitation

    In the authors' previous retrospective study, long-term thromboprophylaxis management and management during high-risk periods were independent protective factors against thrombosis only when considered together, but when analysed separately, none was protective.

    “Long-term thromboprophylaxis management and management during high-risk periods were, moreover, found to be independent protective factors against thrombosis only when considered together but, when analysed separately, none was protective against thrombosis.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Ruffatti, 2009, Risk factors for a first thrombotic event in antiphospholipid antibody carriers. A multicentre, retrospective follow-up study., Ann Rheum Dis source

  • May combine two claims.

    Interpretationreasoning

    Most of the pregnant women being studied were protected by LDA ± low molecular weight heparin prophylactic treatment, which probably explains why pregnancy was not associated with thrombosis.

    “This is probably due to the fact that most of the pregnant women being studied here were protected by LDA ± low molecular weight heparin prophylactic treatment.”
    Quote in the paperSubstantial claim
5 of 5

  • The paper relies on this without support.

    Drug compliance self-reports accurately reflect actual compliance.

    “Drug compliance was monitored on the basis of self-reports by participants.”

  • The paper relies on this without support.

    The study cohort is representative of confirmed antiphospholipid antibody carriers without a history of thrombosis.

    “A cohort of 258 Caucasian confirmed aPL carriers (223 women and 35 men, mean±SD age 40.9±11.1 years, range 18-65) without a history of thrombosis were prospectively evaluated between 15 October 2004 and 15 October 2008 for a mean±SD follow-up of 35.0±11.9months (range 1-48).”

  • The paper relies on this without support.

    The association between high-risk prophylaxis and reduced thrombosis is not due to confounding by indication or other unmeasured confounders.

    “Thromboembolic events were significantly reduced only when antithrombotic prophylaxis was administered in high-risk situations (OR 0.1, 95% CI 0.01 to 0.9, p<0.05).”
3 of 3

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?

  • In women with systemic lupus erythematosus and prior obstetric antiphospholipid syndrome, the protective effect of low-dose aspirin is supported by three retrospective studies that included a minority of patients with systemic lupus erythematosus.

    “Studies of women with SLE and prior obstetric APS are scarce, but the protective effect of LDA was supported by three retrospective studies that included a minority of patients with SLE.18–20”

    From EULAR recommendations for the management of antiphospholipid syndrome in adults (2019) · cites this paper as [20]

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

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • 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”

    From Incidence of a first thromboembolic event in asymptomatic carriers of high-risk antiphospholipid antibody profile: a multicenter prospective study (2011) · cites this paper as [15]

    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

  • 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”

    From Incidence of a first thromboembolic event in asymptomatic carriers of high-risk antiphospholipid antibody profile: a multicenter prospective study (2011) · cites this paper as [15]

    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

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.

  • Abstract and methods name different multivariate models

    Minor

    The abstract says the independent risk factors were identified by logistic regression, whereas the statistical methods specify a Cox proportional hazards model for the multivariate analysis.

1 of 1

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Authors
Ruffatti, A., Del Ross, T., Ciprian, M., Bertero, M. T., Salvatore, S., Scarpato, S., Montecucco, C., Rossi, S., Caramaschi, P., Biasi, D., Doria, A., Rampudda, M., Monica, N., Fischetti, F., Picillo, U., Brucato, A., Salvan, E., Vittorio, P., Meroni, P., & Tincani, A.
Affiliations
  • University of Padua (IT)
  • A. O. Ordine Mauriziano di Torino (IT)
  • University of Pavia (IT)
  • University of Verona (IT)
  • University of Brescia (IT)
  • University of Campania "Luigi Vanvitelli" (IT)
Corresponding author
Ruffatti, Amelia
ORCID
Venue
Annals of the Rheumatic Diseases
Publisher
Elsevier BV
Published
2011-06
Volume
70
Issue
6
Pages
1083-1086
ISSN
0003-4967 (ISSN-L)
DOI
10.1136/ard.2010.142042
OpenAlex
W2104266044
Cited by
184
References
24
Citations by year
2026: 2 · 2025: 2 · 2024: 7 · 2023: 19 · 2022: 17 · 2021: 15 · 2020: 13 · 2019: 17 · 2018: 8 · 2017: 12 · 2016: 16 · 2015: 9 · 2014: 11 · 2013: 14 · 2012: 13
FWCI
9.57
Type
journal article
Language
en
Update notices
erratum (2011-08-01)
Open access
Licence
Locations
  • Annals of the Rheumatic Diseases (publishedVersion)
  • PubMed (publishedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
  • ArTS Archivio della ricerca di Trieste (University of Trieste https://www.units.it/) (submittedVersion)
  • HighWire Press Open Archive (submittedVersion)
  • Padua Research Archive (University of Padova) (submittedVersion)
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
antiphospholipid antibodies, thrombosis, thromboprophylaxis, hypertension, lupus anticoagulant, risk factors, venous thrombosis, arterial thrombosis, transient ischemic attack, thrombosis incidence
MeSH terms
Adult, Autoantibodies, Epidemiologic Methods, Female, Humans, Hypertension, Male, Middle Aged, Thrombosis, Lupus Coagulation Inhibitor, Antiphospholipid Syndrome, Antibodies, Antiphospholipid, Young Adult

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