Cardiovascular risk factors are major determinants of thrombotic risk in patients with the lupus anticoagulant
Open accessAbstract
BACKGROUND: Patients with the lupus anticoagulant (LA) are at an increased risk of thrombotic events, which in turn increase the risk of death. Understanding the determinants of thrombotic risk in patients with LA may pave the way towards targeted thromboprophylaxis. In the Vienna Lupus Anticoagulant and Thrombosis Study (LATS), we systematically evaluate risk factors for thrombotic events in patients with LA. METHODS: We followed 150 patients (mean age: 41.3 years, female gender: n = 122 (81.3%), history of thrombosis or pregnancy complications: n = 111 (74.0%)), who tested repeatedly positive for LA until development of thrombosis, death, or censoring. The primary endpoint was a composite of arterial or venous thrombotic events (TEs). RESULTS: During a median follow-up of 9.5 years (range: 12 days-13.6 years) and 1076 person-years, 32 TEs occurred (arterial: n = 16, venous: n = 16; cumulative 10-year TE incidence: 24.3%). A prolonged lupus-sensitive activated partial thromboplastin time (aPTT-LA) (adjusted subdistribution hazard ratio (SHR) = 2.31, 95% CI: 1.07--5.02), diabetes (adjusted SHR = 4.39, 95% CI: 1.42-13.57), and active smoking (adjusted SHR = 2.31, 95% CI: 1.14-5.02) emerged as independent risk factors of both arterial and venous thrombotic risk. A risk model that includes a prolonged lupus-sensitive aPTT, smoking, and diabetes enabled stratification of LA patients into subgroups with a low, intermediate, and high risk of thrombosis (5-year TE risk of 9.7% (n = 77), 30.9% (n = 51), and 56.8% (n = 22). CONCLUSIONS: Long-term thrombotic risk in patients with LA is clustered within subjects harboring typical cardiovascular risk factors in addition to a prolonged lupus-sensitive aPTT, whereas patients with none of these risk factors represent a large subgroup with a low risk of thrombosis.
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TL;DR
In a prospective cohort of 150 patients with persistently positive lupus anticoagulant, 32 thrombotic events occurred over a median 9.5 years and 1076 person-years, with a cumulative 10-year thrombotic event incidence of 24.3%. Diabetes, active smoking, and a prolonged lupus-sensitive aPTT independently predicted thrombosis, whereas disease-defining antiphospholipid antibodies were associated with prior but not future thrombotic risk.
Key findings
- During median follow-up of 9.5 years (range 12 days–13.6 years) and 1076 person-years, 32 thrombotic events occurred (arterial n=16, venous n=16); cumulative 10-year thrombotic event incidence was 24.3% (95% CI 17.0–32.5).
- Independent risk factors for thrombotic risk were prolonged lupus-sensitive aPTT (adjusted SHR=2.31, 95% CI 1.07–5.02), diabetes (adjusted SHR=4.39, 95% CI 1.42–13.57), and active smoking (adjusted SHR=2.31, 95% CI 1.14–5.02).
- A point-based model assigning 2 points for diabetes and 1 point each for smoking and prolonged lupus-sensitive aPTT stratified patients into 0, 1, or ≥2 point groups with 10-year thrombotic event risks of 9.7% (n=77), 30.9% (n=51), and 56.8% (n=22); Harrell’s C was 0.72.
- Disease-defining antibodies were associated with anamnestic thrombosis, e.g. triple positivity OR=2.5 (95% CI 1.2–5.1, p=0.01), but not consistently with prospective thrombosis, e.g. triple positivity by ISTH cut-off SHR=1.53 (95% CI 0.77–3.04, p=0.226).
Methods
- Prospective, single-center, biobank-based observational cohort: the Vienna Lupus Anticoagulant and Thrombosis Study (LATS), enrolling 150 adults who tested repeatedly positive for LA (two positive tests at least 12 weeks apart); mean age 41.3 years, 122 (81.3%) female, 111 (74.0%) with history of thrombosis or pregnancy complications.
- Primary endpoint was a composite of symptomatic, objectively confirmed arterial and/or venous thrombosis; patients were followed until thrombosis, death, or censoring, and patients who became LA negative during follow-up (n=11) were censored at first negative LA test.
- Analysis used cumulative incidence estimators with death as a competing risk, Gray’s test, and uni-/multivariable Fine–Gray proportional subdistribution hazards models; backward selection (p for exclusion=0.10) built the risk model, with internal validation by Harrell’s C statistic and calibration checks.
Limitations
- The paper states that results are not directly generalizable to other APS groups, such as patients with SLE or patients positive for aCL or aβ2-GPI without LA; that the observational design cannot provide a valid estimate of anticoagulation benefit because reverse causality likely confounded baseline anticoagulation; that the empirical risk stratification rule was not externally validated; and that the point-based rule loses information versus the full multivariable model (diabetes coefficient rounded from 1.6 to 2 points).
- Evident from the text: the cohort is single-center and highly selected for LA-positive patients, with a high proportion of prior thrombosis/APS, and only 32 events occurred, limiting precision and power for subgroup and event-type sensitivity analyses.
Model-written summary. Check it against the paper before relying on it.
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Cites
Statistics
Claims the paper makes
15 of 30 cited sources checked · 8 supported · 1 flagged · accuracy not yet measured
- Premisecitation
A considerable proportion of patients with LA will not develop thrombosis despite the presence of aPL-associated autoantibodies at high titers.
“Further, a considerable proportion of patients with LA will not develop thrombosis despite the presence of aPL-associated autoantibodies at high titers [7].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [7] Galli M, Borrelli G, Jacobsen EM, Marfisi RM, Finazzi G, Marchioli R, Wisloff F, Marziali S, Morboeuf O, Barbui T. Clinical significance of different antiphospholipid antibodies in the WAPS (warfarin in the antiphospholipid syndrome) study. Blood. 2007;110(4):1178–83. source
The section on IgG aPL antibodies in LA-positive patients reports that 32 of 38 patients with high aPT levels and 33 of 37 with high anti-β2GPI levels had a history of thrombosis; some in each group therefore had no such history. The Clinical characteristics section reports thrombosis during a median 3.67-year follow-up in 15 of 112 patients, but it does not establish that a considerable proportion of high-titer, LA-positive patients will never develop thrombosis. (LLM, conf=0.81)
Experimental — accuracy not yet measured
- Interpretationcitation
These results add to the growing body of evidence that shows inconsistent associations between aPL-associated autoantibodies and anamnestic thrombotic risk.
“These results confirm and validate several previous reports that have implicated these antibodies in the pathogenesis of APS [9, 10, 12, 13, 29, 30], but they also add to the growing body of evidence that shows inconsistent associations between aPL-associated autoantibodies and anamnestic thrombotic risk [3, 16].”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [3] Chaturvedi S, McCrae KR. The antiphospholipid syndrome: still an enigma. Hematology Am Soc Hematol Educ Program. 2015;2015(1):53–60. source
- cites [16] Lackner KJ, Muller-Calleja N. Pathogenesis of the antiphospholipid syndrome revisited — time to challenge the dogma. J Thromb Haemost. 2016. source
- Interpretationown data
These results confirm and validate several previous reports that have implicated these antibodies in the pathogenesis of APS.
“These results confirm and validate several previous reports that have implicated these antibodies in the pathogenesis of APS [9, 10, 12, 13, 29, 30], but they also add to the growing body of evidence that shows inconsistent associations between aPL-associated autoantibodies and anamnestic thrombotic risk [3, 16].”
Quote in the paperNot a substantial claim1 of 6 sources checked- cites [9] Pengo V, Ruffatti A, Tonello M, Cuffaro S, Banzato A, Bison E, Denas G, Padayattil JS. Antiphospholipid syndrome: antibodies to Domain 1 of beta2-glycoprotein 1 correctly classify patients at risk. J Thromb Haemost. 2015;13(5):782–7. source
- cites [10] Pengo V, Ruffatti A, Tonello M, Hoxha A, Bison E, Denas G, Padayattil Jose S, Zoppellaro G, Bracco A, Banzato A. Antibodies to Domain 4/5 (Dm4/5) of beta2-glycoprotein 1 (beta2GP1) in different antiphospholipid (aPL) antibody profiles. Thromb Res. 2015;136(1):161–3. source
- cites [12] de Laat B, Pengo V, Pabinger I, Musial J, Voskuyl AE, Bultink IE, Ruffatti A, Rozman B, Kveder T, de Moerloose P, et al. The association between circulating antibodies against domain I of beta2-glycoprotein I and thrombosis: an international multicenter study. J Thromb Haemost. 2009;7(11):1767–73. source
- cites [13] de Laat HB, Derksen RH, Urbanus RT, Roest M, de Groot PG. beta2-glycoprotein I-dependent lupus anticoagulant highly correlates with thrombosis in the antiphospholipid syndrome. Blood. 2004;104(12):3598–602. source
- cites [29] Galli M, Luciani D, Bertolini G, Barbui T. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood. 2003;101(5):1827–32. source
- cites [30] Pengo V, Testa S, Martinelli I, Ghirarduzzi A, Legnani C, Gresele P, Passamonti SM, Bison E, Denas G, Jose SP, et al. Incidence of a first thromboembolic event in carriers of isolated lupus anticoagulant. Thromb Res. 2015;135(1):46–9. source
- Interpretationreasoning
The results are not directly generalizable to other patient groups included in the wide and heterogenic spectrum of APS, such as patients with SLE or patients who are positive for aCL or aβ2-GPI but not LA.
“Consequently, our results are not directly generalizable to other patient groups included in the wide and heterogenic spectrum of APS, such as patients with SLE [34, 38] or patients who are positive for aCL or aβ2-GPI but not LA [39].”
Quote in the paperNot a substantial claim2 of 3 sources checked- cites [34] Sciascia S, Sanna G, Murru V, Roccatello D, Khamashta MA, Bertolaccini ML. GAPSS: the Global Anti-Phospholipid Syndrome Score. Rheumatology (Oxford). 2013;52(8):1397–403. source
The citation [39] is attached to the example of patients positive for aCL or anti-β2GPI but not LA, rather than to the citing authors’ conclusion about generalizability. The Patients section lists all three as separately measured antibodies, and the results treat them as separate risk factors. Our copy does not specifically identify or analyze patients positive for aCL or anti-β2GPI while negative for LA. (LLM, conf=0.78)
Experimental — accuracy not yet measured - cites [38] Sciascia S, Cuadrado MJ, Sanna G, Murru V, Roccatello D, Khamashta MA, Bertolaccini ML. Thrombotic risk assessment in systemic lupus erythematosus: validation of the global antiphospholipid syndrome score in a prospective cohort. Arthritis Care Res (Hoboken). 2014;66(12):1915–20. source
- cites [39] Sciascia S, Sanna G, Murru V, Roccatello D, Khamashta MA, Bertolaccini ML. The global anti-phospholipid syndrome score in primary APS. Rheumatology (Oxford). 2015;54(1):134–8. source
- Findingown data
The 10-year thrombotic risk was estimated at 36.5% in active smokers, compared to 18.8% in ex- or never-smokers (p = 0.022).
“The 10-year thrombotic risk was estimated at 36.5% in active smokers, as compared to 18.8% in ex- or never-smokers (p = 0.022).”
Quote in the paperSubstantial claim
- Findingown data
None of the studied variables was significantly associated with thrombotic risk after adjusting for diabetes, smoking, and prolonged lupus-sensitive aPTT.
“None of the studied variables was significantly associated with thrombotic risk after adjusting for these three variables.”
Quote in the paperSubstantial claim - Findingown data
In adjusted analysis, a prolonged lupus-sensitive aPTT is an independent risk factor for both arterial and venous thrombotic risk (adjusted SHR = 2.31, 95% CI: 1.07-5.02).
“A prolonged lupus-sensitive activated partial thromboplastin time (aPTT-LA) (adjusted subdistribution hazard ratio (SHR) = 2.31, 95% CI: 1.07–-5.02), diabetes (adjusted SHR = 4.39, 95% CI: 1.42–13.57), and active smoking (adjusted SHR = 2.31, 95% CI: 1.14–5.02) emerged as independent risk factors of both arterial and venous thrombotic risk.”
Quote in the paperSubstantial claim - Findingown data
The risk of thrombotic events was comparable between patients with or without a prior history of thrombosis (SHR = 0.94, 95% CI: 0.45-1.95, p = 0.865).
“Risk of TE was comparable between patients with established APS and LA-positive-only patients (SHR = 0.75, 95% CI: 0.36–1.58, p = 0.448), as well as between patients with or without a prior history of thrombosis (SHR = 0.94, 95% CI: 0.45–1.95, p = 0.865).”
Quote in the paperSubstantial claim - Findingown data
In adjusted analysis, diabetes is an independent risk factor for both arterial and venous thrombotic risk (adjusted SHR = 4.39, 95% CI: 1.42-13.57).
“A prolonged lupus-sensitive activated partial thromboplastin time (aPTT-LA) (adjusted subdistribution hazard ratio (SHR) = 2.31, 95% CI: 1.07–-5.02), diabetes (adjusted SHR = 4.39, 95% CI: 1.42–13.57), and active smoking (adjusted SHR = 2.31, 95% CI: 1.14–5.02) emerged as independent risk factors of both arterial and venous thrombotic risk.”
Quote in the paperSubstantial claim - Findingown data
In multivariable analysis, the joint association between diabetes, smoking, and a prolonged lupus-sensitive aPTT ratio and a higher risk of thrombosis prevailed upon inclusion of all reported variables.
“The joint multivariable association between diabetes, smoking, the prolonged lupus-sensitive aPTT ratio and a higher risk of thrombosis prevailed upon inclusion of all reported variables.”
Quote in the paperSubstantial claim - Findingown data
In a univariable competing risk analysis, a prolonged lupus-sensitive aPTT was associated with a higher risk of thrombotic events (SHR per 10 seconds increase = 1.10, 95% CI: 1.00-1.21, p = 0.044).
“In a univariable competing risk analysis, diabetes (subdistribution hazard ratio (SHR) = 5.18, 95% CI: 1.87–14.31, p = 0.002), active smoking (SHR = 2.11, 95% CI: 1.06–4.20, p = 0.034), and a prolonged lupus-sensitive aPTT (SHR per 10 seconds increase = 1.10, 1.00–1.21, p = 0.044) were univariably associated with a higher risk of TE (Table 3).”
Quote in the paperNot a substantial claim - Findingown data
A borderline significant association was observed between an increased baseline IgM-isotype aCL antibody level and a higher risk of thrombotic events (SHR = 1.30, 95% CI: 0.98-1.74, p = 0.068).
“A borderline significant association was observed between an increased baseline IgM-isotype aCL antibody level and a higher risk of TE risk (SHR = 1.30, 95% CI: 0.98–1.74, p = 0.068).”
Quote in the paperNot a substantial claim - Findingown data
The risk of thrombotic events was comparable between patients with established APS and LA-positive-only patients (SHR = 0.75, 95% CI: 0.36-1.58, p = 0.448).
“Risk of TE was comparable between patients with established APS and LA-positive-only patients (SHR = 0.75, 95% CI: 0.36–1.58, p = 0.448), as well as between patients with or without a prior history of thrombosis (SHR = 0.94, 95% CI: 0.45–1.95, p = 0.865).”
Quote in the paperSubstantial claim - Findingown data
The 10-year cumulative risk of thrombotic events was 60.0% in patients who were diabetic at baseline, compared to 21.6% in non-diabetic patients (Gray's test p = 0.002).
“In detail, the 10-year cumulative risk of TE was 60.0% in patients who were diabetic at baseline, as compared to 21.6% in non-diabetic patients (Gray’s test p = 0.002).”
Quote in the paperSubstantial claim - Findingown data
In patients with a lupus-sensitive aPTT above versus at or below the 75th percentile, the 10-year thrombotic risks were 43.7% and 17.6%, respectively (p = 0.004).
“In patients with a lupus-sensitive aPTT > or ≤ the 75th percentile of its distribution (cut-off at 117.5 s (or for the aPTT ratio at 3.4 multiples of the median in healthy individuals)), we observed 10-year thrombotic risks of 43.7% and 17.6%, respectively (p = 0.004, Additional file 9: Figure S2A–C).”
Quote in the paperSubstantial claim - Findingown data
In a univariable competing risk analysis, active smoking was associated with a higher risk of thrombotic events (SHR = 2.11, 95% CI: 1.06-4.20, p = 0.034).
“In a univariable competing risk analysis, diabetes (subdistribution hazard ratio (SHR) = 5.18, 95% CI: 1.87–14.31, p = 0.002), active smoking (SHR = 2.11, 95% CI: 1.06–4.20, p = 0.034), and a prolonged lupus-sensitive aPTT (SHR per 10 seconds increase = 1.10, 1.00–1.21, p = 0.044) were univariably associated with a higher risk of TE (Table 3).”
Quote in the paperSubstantial claim - Findingown data
The backward selection algorithm selected diabetes, smoking, and a prolonged lupus-sensitive aPTT as the variables for the multivariable model.
“The algorithm selected the three variables diabetes, smoking, and a prolonged lupus-sensitive aPTT, and we constructed an empirical risk stratification rule by assigning 2 points for diabetes, and 1 point for each of the risk factors smoking and a prolonged lupus-sensitive aPTT.”
Quote in the paperSubstantial claim - Findingown data
In a univariable competing risk analysis, diabetes was associated with a higher risk of thrombotic events (SHR = 5.18, 95% CI: 1.87-14.31, p = 0.002).
“In a univariable competing risk analysis, diabetes (subdistribution hazard ratio (SHR) = 5.18, 95% CI: 1.87–14.31, p = 0.002), active smoking (SHR = 2.11, 95% CI: 1.06–4.20, p = 0.034), and a prolonged lupus-sensitive aPTT (SHR per 10 seconds increase = 1.10, 1.00–1.21, p = 0.044) were univariably associated with a higher risk of TE (Table 3).”
Quote in the paperSubstantial claim - Findingown data
Twenty-three (74.2%) of the 31 thrombotic events with available antithrombotic therapy data occurred while patients were receiving antithrombotic therapy.
“Twenty-three (74.2%) of these 31 events occurred while patients were receiving antithrombotic therapy (Table 2).”
Quote in the paperSubstantial claim - Findingown data
The joint multivariable association between diabetes, smoking, and a prolonged lupus-sensitive aPTT ratio and a higher risk of thrombosis also held true when adjusting for oral anticoagulation at baseline.
“This also held true when adjusting for oral anticoagulation at baseline (Additional file 11: Table S5).”
Quote in the paperNot a substantial claim - Findingown data
During a median follow-up of 9.5 years and 1076 patient-years, 32 patients developed thrombotic events (arterial: n = 16, venous: n = 16).
“During a median follow-up of 9.5 years (range: 12 days–13.6 years) and 1076 patient years, 32 patients developed TE (arterial: n = 16, venous: n = 16).”
Quote in the paperNot a substantial claim- Rests on an assumption: The composite endpoint of arterial and venous thrombosis is a valid single outcome for risk stratification.
- Findingown data
The cumulative 1-, 5-, 10-, and 15-year incidences of thrombotic events accounting for competing mortality were 4.0%, 13.3%, 24.3%, and 27.6%, respectively.
“The cumulative 1-, 5-, 10-, and 15-year incidences of TE accounting for competing mortality were 4.0% (95% CI: 1.7–8.1), 13.3% (95% CI: 8.3–19.4), 24.3% (95% CI: 17.0–32.5), and 27.6% (95% CI: 19.3–36.6), respectively (Additional file 8: Figure S1).”
Quote in the paperNot a substantial claim- Rests on an assumption: The composite endpoint of arterial and venous thrombosis is a valid single outcome for risk stratification.
- Findingown data
Oral anticoagulation with a VKA at baseline was not associated with prospective thrombotic risk (SHR = 0.93, 95% CI: 0.47-1.86, p = 0.839).
“Oral anticoagulation with a VKA at baseline was not associated with prospective thrombotic risk (SHR = 0.93, 95% CI: 0.47–1.86, p = 0.839, Additional file 10: Figure S3A).”
Quote in the paperSubstantial claim - Findingown data
Very strong associations were found between the presence of typical cardiovascular risk factors at baseline, such as diabetes and smoking, with an excessively increased risk of thrombosis in the cohort.
“Interestingly, we found very strong associations between the presence of typical cardiovascular risk factors at baseline, such as diabetes and smoking, with an excessively increased risk of thrombosis in our cohort.”
Quote in the paperSubstantial claim - Findingown data
No association was observed between IgG-isotype antibodies against domain 1 of β2-GPI and prospective thrombotic risk in the overall cohort or in subgroup analyses in patients with and without a prior history of thrombosis.
“However, also with this specific antibody we did not observe an association with prospective thrombotic risk in the overall cohort or when performing subgroup analyses in patients with and without a prior history of thrombosis.”
Quote in the paperSubstantial claim - Findingown data
A risk model that includes a prolonged lupus-sensitive aPTT, smoking, and diabetes enabled stratification of LA patients into subgroups with a low, intermediate, and high risk of thrombosis (5-year TE risk of 9.7% (n = 77), 30.9% (n = 51), and 56.8% (n = 22)).
“A risk model that includes a prolonged lupus-sensitive aPTT, smoking, and diabetes enabled stratification of LA patients into subgroups with a low, intermediate, and high risk of thrombosis (5-year TE risk of 9.7% (n = 77), 30.9% (n = 51), and 56.8% (n = 22).”
Quote in the paperSubstantial claim- Rests on an assumption: The composite endpoint of arterial and venous thrombosis is a valid single outcome for risk stratification.
- Findingown data
Among the studied antibodies, IgG-isotype antibodies against domain 1 of β2-GPI showed the strongest and most consistent associations with both anamnestic risk of thrombosis and pregnancy complications.
“Among the studied antibodies, IgG-isotype antibodies against domain 1 of β2-GPI showed the strongest and most consistent associations with both anamnestic risk of thrombosis and pregnancy complications.”
Quote in the paperNot a substantial claim - Findingown data
Among non-canonical aPL-associated antibodies, such as antibodies against protein Z or prothrombin, only a weak association was observed between higher IgM-isotype antibodies against protein Z and a higher risk of anamnestic thrombosis.
“Among non-canonical aPL-associated antibodies [11], such as antibodies against protein Z or prothrombin, we only observed a weak association between higher IgM-isotype antibodies against protein Z and a higher risk of anamnestic thrombosis.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [11] Bertolaccini ML, Sciascia S, Murru V, Garcia-Fernandez C, Sanna G, Khamashta MA. Prevalence of antibodies to prothrombin in solid phase (aPT) and to phosphatidylserine-prothrombin complex (aPS/PT) in patients with and without lupus anticoagulant. Thromb Haemost. 2013;109(2):207–13. source
- Findingown data
In the baseline analysis, univariable associations were found between some aPL-associated autoantibodies and the anamnestic risk of thrombosis.
“In the baseline analysis, we found univariable associations between some aPL-associated autoantibodies and the anamnestic risk of thrombosis.”
Quote in the paperNot a substantial claim - Findingown data
In adjusted analysis, active smoking is an independent risk factor for both arterial and venous thrombotic risk (adjusted SHR = 2.31, 95% CI: 1.14-5.02).
“A prolonged lupus-sensitive activated partial thromboplastin time (aPTT-LA) (adjusted subdistribution hazard ratio (SHR) = 2.31, 95% CI: 1.07–-5.02), diabetes (adjusted SHR = 4.39, 95% CI: 1.42–13.57), and active smoking (adjusted SHR = 2.31, 95% CI: 1.14–5.02) emerged as independent risk factors of both arterial and venous thrombotic risk.”
Quote in the paperSubstantial claim - Findingown data
A simple empirical risk stratification rule consisting of two clinical and one laboratory variable (diabetes, smoking, and a prolonged lupus-sensitive aPTT ratio) allowed stratification of patients into subgroups with a very high and very low risk of thrombosis.
“Notably, a simple empirical risk stratification rule consisting of two clinical and one laboratory variable allowed us to stratify our patients into subgroups with a very high and very low risk of thrombosis.”
- Also stated in: § Discussion · hedged
“Based on our univariable findings and a prespecified model-building algorithm, we identified a simple empirical risk stratification rule including the variables diabetes, smoking, and a prolonged lupus-sensitive aPTT ratio which could discriminate our patients into subgroups with a very high and very low risk of thrombosis.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · hedged
- Findingown data
Triple positivity was not consistently associated with the risk of developing thrombosis.
“This held true also for “triple positivity.””
Quote in the paperSubstantial claim - Findingown data
A prolongation of a lupus-sensitive aPTT was strongly associated with a higher prospective TE risk, and this association prevailed after controlling for oral anticoagulation and other risk factors including diabetes and smoking.
“Interestingly, a prolongation of a lupus-sensitive aPTT (PTT-LA, Diagnostica Stago, Asniere-sur-Seine, France), which is used as a screening tool for making the diagnosis of LA at our center, was also strongly associated with a higher prospective TE risk, and this association prevailed after controlling for oral anticoagulation and other risk factors including diabetes and smoking.”
- Also stated in: § Conclusions · plain
“Moreover, a very long lupus-sensitive aPTT was predictive for the occurrence of TE in these patients as well.”
- Also stated in: § Conclusions · plain
“These associations were independent of anticoagulation.”
Quote in the paperSubstantial claim - Also stated in: § Conclusions · plain
- Findingown data
Some miscalibration was observed for 1- and 5-year thrombotic risk prediction in patients with 1 or ≥2 points, where the rule somewhat over- and underpredicted the observed thrombotic risk.
“Some miscalibration was observed for 1- and 5-year thrombotic risk prediction in patients with 1 or ≥2 points, where the rule somewhat over- and underpredicted the observed thrombotic risk.”
Quote in the paperNot a substantial claim - Findingown data
Disease-defining autoantibodies such as aCL or aβ2-GPI were associated with anamnestic thrombotic risk.
“While disease-defining autoantibodies such as aCL or aβ2-GPI were associated with anamnestic thrombotic risk, these variables appeared to harbor very limited prognostic information on prospective, long-term thrombotic outcomes over a median follow-up period of nearly 10 years.”
- Also stated in: § Conclusions · boosted
“Disease-defining antibodies, such as those against cardiolipin or β2-GPI (including those against domain I), showed a strong association with anamnestic risk of thrombosis; however, they did not predict the future occurrence of TE in this LA-positive patient population.”
Quote in the paperNot a substantial claim - Also stated in: § Conclusions · boosted
- Findingown data
None of the studied aPL-associated autoantibodies were consistently associated with the risk of developing thrombosis.
“In our study, we were surprised to observe that none of the studied aPL-associated autoantibodies were consistently associated with the risk of developing thrombosis. This held true also for “triple positivity.””
Quote in the paperSubstantial claim - Findingown data
Disease-defining autoantibodies such as aCL or aβ2-GPI appeared to harbor very limited prognostic information on prospective, long-term thrombotic outcomes over a median follow-up period of nearly 10 years.
“While disease-defining autoantibodies such as aCL or aβ2-GPI were associated with anamnestic thrombotic risk, these variables appeared to harbor very limited prognostic information on prospective, long-term thrombotic outcomes over a median follow-up period of nearly 10 years.”
- Also stated in: § Conclusions · plain
“Disease-defining antibodies, such as those against cardiolipin or β2-GPI (including those against domain I), showed a strong association with anamnestic risk of thrombosis; however, they did not predict the future occurrence of TE in this LA-positive patient population.”
Quote in the paperSubstantial claim - Also stated in: § Conclusions · plain
- Findingown data
In patients with persistently positive LA with or without established APS, the study observed a high incidence of thrombotic complications.
“In this prospective study on patients with persistently positive LA with or without established APS, we observed a high incidence of thrombotic complications.”
Quote in the paperSubstantial claim - Findingown data
A weak association was observed between exposure to statins and a higher risk of thrombosis.
“Further, we have observed a weak association between exposure to statins and a higher risk of thrombosis.”
Quote in the paperNot a substantial claim - Findingown data
Two-thirds of the LA-positive patients in this study had a history of at least one thrombotic event.
“Two-thirds of the LA-positive patients in this study had a history of at least one thrombotic event, and venous events were the predominant anamnestic event type.”
Quote in the paperNot a substantial claim - Findingown data
Venous events were the predominant anamnestic event type in the LA-positive patients in this study.
“Two-thirds of the LA-positive patients in this study had a history of at least one thrombotic event, and venous events were the predominant anamnestic event type.”
Quote in the paperNot a substantial claim - Findingown data
The risk stratification rule could identify a very large subgroup of patients representing 50% of the patient population who had a very low risk of thrombosis with the current management strategy, namely treating patients with a history of thrombosis with oral anticoagulation.
“While this rule still has to be validated in an external cohort, its most promising feature is that it could identify a very large subgroup of patients representing 50% of our patient population who had a very low risk of thrombosis with the current management strategy, namely treating patients with a history of thrombosis with oral anticoagulation.”
- Also stated in: § Conclusions · plain
“A simple empirical risk stratification rule can identify a very large subgroup of LA-positive patients with a very low prospective risk of thrombosis.”
Quote in the paperSubstantial claim - Also stated in: § Conclusions · plain
- Findingown data
Thrombotic risk was highly clustered within subjects who had typical cardiovascular risk factors, such as diabetes or active smoking, and a very prolonged lupus-sensitive aPTT.
“A systematic analysis of risk factors for the occurrence of thrombosis showed that thrombotic risk was highly clustered within subjects who had (1) typical cardiovascular risk factors, such as diabetes or active smoking, and (2) a very prolonged lupus-sensitive aPTT.”
Quote in the paperSubstantial claim - Findingown data
Approximately three out of four thrombotic events occurred while patients were receiving antithrombotic medication with VKA, LMWH, and/or LDA.
“Importantly, approximately three out of four thrombotic events occurred while patients were receiving antithrombotic medication with VKA, LMWH, and/or LDA, suggesting that episodes of hypercoagulability in LA-positive patients can induce overt thrombosis despite antithrombotic therapy.”
Quote in the paperSubstantial claim - Findingown data
A smaller subgroup representing about 15% of the population experienced an excessive thrombotic risk.
“Conversely, we identified a smaller subgroup representing about 15% of our population who experienced an excessive thrombotic risk.”
Quote in the paperSubstantial claim - Findingown data
Patients with a history of thrombosis had a substantially higher probability of being on oral anticoagulation.
“Indeed, patients with a history of thrombosis had a substantially higher probability of being on oral anticoagulation, so anticoagulation may rather reflect the decision of individual physicians to anticoagulate those patients with the highest perceived risk of thrombosis.”
Quote in the paperSubstantial claim - Findingown data
In this observational study, patients who were anticoagulated at baseline had a similar risk of prospective thrombosis as patients who were not anticoagulated.
“In this observational study, patients who were anticoagulated at baseline had a similar risk of prospective thrombosis as patients who were not anticoagulated.”
Quote in the paperNot a substantial claim - Findingown data
The three-category point-based model (Model 3) could stratify patients into subgroups with a very low and very high risk of thrombosis (10-year risk of TE in patients with 0, 1, or ≥2 points: 9.7%, 30.9%, and 56.8%, respectively).
“The three-category point-based model (Model 3) could stratify patients into subgroups with a very low and very high risk of thrombosis (10-year risk of TE in patients with 0 (n = 77), 1 (n = 51), or ≥2 (n = 22) points: 9.7%, 30.9%, and 56.8%, respectively; Fig. 1).”
Quote in the paperSubstantial claim - Premisecitation
Patients with lupus anticoagulant (LA) are at increased risk of arterial and venous thrombosis.
“Autoantibodies directed against phospholipid-binding plasma proteins (also known as antiphospholipid (aPL) antibodies), detected through coagulation assays such as the lupus anticoagulant (LA) and through immunoassays such as anticardiolipin (aCL) or anti-β2-glycoprotein I (aβ2-GPI), confer an increased risk of arterial and venous thrombosis [1].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1] de Groot PG, Lutters B, Derksen RH, Lisman T, Meijers JC, Rosendaal FR. Lupus anticoagulants and the risk of a first episode of deep venous thrombosis. J Thromb Haemost. 2005;3(9):1993–7. source
- Premisecitation
The recently published results from the Piedmont cohort study found a tenfold increased thrombotic risk in LA patients with diabetes.
“This is consistent with the recently published results from the Piedmont cohort study, which found a tenfold increased thrombotic risk in LA patients with diabetes [32].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [32] Bazzan M, Vaccarino A, Stella S, Sciascia S, Montaruli B, Bertero MT, Carignola R, Roccatello D. Patients with antiphosholipid syndrome and thrombotic recurrences: a real world observation (the Piedmont cohort study). Lupus. 2015;25. doi: 10.1177/0961203315617538 source
- Study design and conductown data
The present analysis cannot provide a valid estimate for the potential benefit of anticoagulation in LA-positive patients.
“Second, our present analysis cannot provide a valid estimate for the potential benefit of anticoagulation in LA-positive patients.”
Quote in the paperSubstantial claim - Interpretationown data
These findings do not support the concept that antibodies against protein Z or prothrombin correctly identify LA positive patients with a history of thrombosis.
“Collectively, these findings do not support the concept that antibodies against protein Z or prothrombin correctly identify LA positive patients with a history of thrombosis.”
Quote in the paperSubstantial claim - Interpretationown data
Episodes of hypercoagulability in LA-positive patients can induce overt thrombosis despite antithrombotic therapy.
“Importantly, approximately three out of four thrombotic events occurred while patients were receiving antithrombotic medication with VKA, LMWH, and/or LDA, suggesting that episodes of hypercoagulability in LA-positive patients can induce overt thrombosis despite antithrombotic therapy.”
Quote in the paperSubstantial claim - Interpretationown data
Anticoagulation may rather reflect the decision of individual physicians to anticoagulate those patients with the highest perceived risk of thrombosis.
“Indeed, patients with a history of thrombosis had a substantially higher probability of being on oral anticoagulation, so anticoagulation may rather reflect the decision of individual physicians to anticoagulate those patients with the highest perceived risk of thrombosis.”
Quote in the paperSubstantial claim - Interpretationreasoning
This is consistent with the hypothesis that these risk factors represent the necessary "second hit" for eliciting thrombosis in patients with LA.
“This is consistent with the hypothesis that these risk factors represent the necessary “second hit” for eliciting thrombosis in patients with LA.”
Quote in the paperSubstantial claim - Interpretationown data
Established risk factors for vascular events in the general population also turned out to be relevant in patients with LA.
“We conclude that established risk factors for vascular events in the general population also turned out to be relevant in patients with LA.”
Quote in the paperSubstantial claim - Interpretationown data
The results suggest that, above standard anticoagulation, interventions to control and improve metabolic status and smoking habits might influence the rates of future TE in patients with known persistent LA.
“In conclusion, our results suggest that, above standard anticoagulation, interventions to control and improve metabolic status and smoking habits might influence the rates of future TE in patients with known persistent LA.”
Quote in the paperSubstantial claim - Study design and conductreasoning
Because prospective data in LA-positive patients are scarce, the empirical risk stratification rule could not yet be validated in an external cohort.
“Third, because prospective data in LA-positive patients are scarce, we could not yet validate our empirical risk stratification rule in an external cohort.”
Quote in the paperNot a substantial claim
- May combine two claims. 17
- Classified as probably not a substantial claim. 12
May combine two claims.
PremisecitationWhile triple positivity has been shown to be a significant thrombotic risk factor in the WAPS study, several more recent prospective cohorts have also observed a lack of association between triple positivity or other LA-related autoantibodies and thrombosis.
“While triple positivity has been shown to be a significant thrombotic risk factor in the WAPS study [7], several more recent prospective cohorts have also observed a lack of association between triple positivity or other LA-related autoantibodies and thrombosis [30, 32, 33].”
Quote in the paperSubstantial claim2 of 4 sources checked- cites [7] Galli M, Borrelli G, Jacobsen EM, Marfisi RM, Finazzi G, Marchioli R, Wisloff F, Marziali S, Morboeuf O, Barbui T. Clinical significance of different antiphospholipid antibodies in the WAPS (warfarin in the antiphospholipid syndrome) study. Blood. 2007;110(4):1178–83. 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 [30] Pengo V, Testa S, Martinelli I, Ghirarduzzi A, Legnani C, Gresele P, Passamonti SM, Bison E, Denas G, Jose SP, et al. Incidence of a first thromboembolic event in carriers of isolated lupus anticoagulant. Thromb Res. 2015;135(1):46–9. source
- cites [32] Bazzan M, Vaccarino A, Stella S, Sciascia S, Montaruli B, Bertero MT, Carignola R, Roccatello D. Patients with antiphosholipid syndrome and thrombotic recurrences: a real world observation (the Piedmont cohort study). Lupus. 2015;25. doi: 10.1177/0961203315617538 source
- cites [33] Amory CF, Levine SR, Brey RL, Gebregziabher M, Tuhrim S, Tilley BC, Simpson AC, Sacco RL, Mohr JP. Antiphospholipid antibodies and recurrent thrombotic events: persistence and portfolio. Cerebrovasc Dis. 2015;40(5-6):293–300. source
Split into 2 atoms — 0 confirmed, 1 partially supported, 1 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
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationIn vivo, a complex interplay of aPL antibodies with coagulation factors, platelets, and the vessel wall induces a hypercoagulable state that can lead to overt thrombosis and/or adverse pregnancy outcomes.
“Conversely, in vivo, a complex and still enigmatic interplay of these antibodies with coagulation factors, platelets, and the vessel wall induces a hypercoagulable state that can lead to overt thrombosis and/or adverse pregnancy outcomes [3].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [3] Chaturvedi S, McCrae KR. The antiphospholipid syndrome: still an enigma. Hematology Am Soc Hematol Educ Program. 2015;2015(1):53–60. source
Classified as probably not a substantial claim.
PremisecitationIt is currently unclear which patient groups are at the highest risk for the development of thrombotic complications.
“While anticoagulation may reduce the risk of thrombosis, it is currently unclear which patient groups are at the highest risk for the development of thrombotic complications [3].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [3] Chaturvedi S, McCrae KR. The antiphospholipid syndrome: still an enigma. Hematology Am Soc Hematol Educ Program. 2015;2015(1):53–60. source
The Assessment of thrombotic risk section says identifying individuals at greatest risk remains challenging, particularly when predicting first thrombosis in asymptomatic aPL carriers. But the Conclusions identify patients with triple-positive antiphospholipid antibodies as having the highest risk of clinical events, so the claim overstates how little is known about high-risk groups. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThe occurrence of thrombosis in patients with LA is associated with an excessive increase in the risk of death, leading to impaired relative survival compared to an age- and sex-matched reference population.
“Cervera et al. and our group have recently demonstrated that the occurrence of thrombosis in patients with LA is associated with an excessive increase in the risk of death, which in turn leads to a significantly impaired relative survival of these patients in comparison to an age- and sex-matched reference population [5, 6].”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [5] Gebhart J, Posch F, Koder S, Perkmann T, Quehenberger P, Zoghlami C, Ay C, Pabinger I. Increased mortality in patients with the lupus anticoagulant: the Vienna Lupus Anticoagulant and Thrombosis Study (LATS). Blood. 2015;125(22):3477–83. source
- cites [6] Cervera R, Serrano R, Pons-Estel GJ, Ceberio-Hualde L, Shoenfeld Y, de Ramon E, Buonaiuto V, Jacobsen S, Zeher MM, Tarr T, et al. Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis. 2015;74(6):1011–8. source
The Mortality and causes of death section (page unavailable) reports that severe thromboses caused 36.5% of deaths and that the APS cohort had an unadjusted standardized mortality ratio of 1.8 versus the general population. It does not establish that thrombosis specifically increased mortality among patients with lupus anticoagulant (LA), or report relative survival against an age- and sex-matched reference population. The Discussion (page unavailable) says no clinical or immunological parameter was identified as prognostic for mortality. (LLM, conf=0.88)
Experimental — accuracy not yet measured
May combine two claims.
FindingcitationThe relative frequencies of arterial and venous events as well as the proportion of patients receiving anticoagulation while developing an event were very similar to the results of the Euro-Phospholipid study.
“Further, the relative frequencies of arterial and venous events as well as the proportion of patients receiving anticoagulation while developing an event were very similar to the results of the Euro-Phospholipid study [6].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [6] Cervera R, Serrano R, Pons-Estel GJ, Ceberio-Hualde L, Shoenfeld Y, de Ramon E, Buonaiuto V, Jacobsen S, Zeher MM, Tarr T, et al. Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis. 2015;74(6):1011–8. source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationA risk score for anamnestic thrombotic risk in patients with SLE, the Global Anti-Phospholipid Syndrome Score (GAPSS), includes two general cardiovascular risk factors: hypertension and hyperlipidemia.
“Further, a risk score for anamnestic thrombotic risk in patients with SLE, the Global Anti-Phospholipid Syndrome Score (GAPSS), includes two general cardiovascular risk factors: hypertension and hyperlipidemia [34].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [34] Sciascia S, Sanna G, Murru V, Roccatello D, Khamashta MA, Bertolaccini ML. GAPSS: the Global Anti-Phospholipid Syndrome Score. Rheumatology (Oxford). 2013;52(8):1397–403. source
May combine two claims.
FindingcitationThe 10-year cumulative TE incidence of 24.3% compares well to the thrombotic risk observed in the WAPS study and the Euro-Phospholipid Project registry, but was lower than the value in the Piedmont cohort study and higher than that in the study by Pengo et al.
“The 10-year cumulative TE incidence of 24.3% compares well to the thrombotic risk observed in the WAPS study [31] and the very large Euro-Phospholipid Project registry [6], but was lower than the value in the recently published Piedmont cohort study [32] and higher than that in the recently published study by Pengo et al. [30].”
Quote in the paperNot a substantial claim2 of 3 sources checked- cites [31] Finazzi G, Marchioli R, Brancaccio V, Schinco P, Wisloff F, Musial J, Baudo F, Berrettini M, Testa S, D'Angelo A, et al. A randomized clinical trial of high-intensity warfarin vs. conventional antithrombotic therapy for the prevention of recurrent thrombosis in patients with the antiphospholipid syndrome (WAPS). J Thromb Haemost. 2005;3(5):848–53. source
- cites [6] Cervera R, Serrano R, Pons-Estel GJ, Ceberio-Hualde L, Shoenfeld Y, de Ramon E, Buonaiuto V, Jacobsen S, Zeher MM, Tarr T, et al. Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis. 2015;74(6):1011–8. source
- cites [32] Bazzan M, Vaccarino A, Stella S, Sciascia S, Montaruli B, Bertero MT, Carignola R, Roccatello D. Patients with antiphosholipid syndrome and thrombotic recurrences: a real world observation (the Piedmont cohort study). Lupus. 2015;25. doi: 10.1177/0961203315617538 source
May combine two claims.
PremisecitationPreclinical evidence from animal models has demonstrated that the presence of LA-related autoantibodies alone is insufficient for causing overt thrombosis, and a "second hit" such as inflammation or infection may be necessary to transform the prothrombotic potential induced by LA-related autoantibodies into overt thrombosis.
“Second, preclinical evidence from animal models has demonstrated that the presence of LA-related autoantibodies alone is insufficient for causing overt thrombosis, and a “second hit” such as inflammation or infection may be necessary to transform the prothrombotic potential induced by LA-related autoantibodies into overt thrombosis [35].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [35] Mackworth-Young CG. Antiphospholipid syndrome: multiple mechanisms. Clin Exp Immunol. 2004;136(3):393–401. 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
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataA weak multivariable association between exposure to statins and a higher risk of thrombosis was observed.
“However, a weak multivariable association between exposure to statins and a higher risk of thrombosis was observed.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataDeath was present as a competing risk in this population, with 12 patients having died during follow-up without developing thrombotic events.
“With 12 patients having died during follow-up without developing TE, death was clearly present as a competing risk in this population.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataAfter a median follow-up interval of nearly 10 years and more than 1000 person-years spent at risk of thrombosis and death, a high incidence of thrombotic complications was observed despite the fact that the majority of patients with a history of thrombosis were on anticoagulation therapy.
“After a median follow-up interval of nearly 10 years and more than 1000 person-years spent at risk of thrombosis and death, we observed a high incidence of thrombotic complications despite the fact that the majority of patients with a history of thrombosis were on anticoagulation therapy.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn a sensitivity analysis estimating the risk of arterial and venous prospective events separately, diabetes and smoking appeared to be more relevant for predicting arterial events, whereas the prolonged lupus-sensitive aPTT was more associated with the occurrence of venous events.
“In a sensitivity analysis estimating the risk of arterial and venous prospective events separately, we could observe that diabetes and smoking appeared to be more relevant for predicting arterial events, whereas the prolonged lupus-sensitive aPTT was more associated with the occurrence of venous events.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataBoth hypertension and dyslipidemia were strongly correlated with diabetes in the study.
“Both hypertension and dyslipidemia were strongly correlated with diabetes in our study.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataTwo-thirds of the patients with a history of thrombosis were on oral anticoagulants at baseline.
“Two-thirds of the patients with a history of thrombosis were on oral anticoagulants at baseline, which reflects the decision of individual physicians to anticoagulate these patients due to a high perceived risk of recurrent thrombosis.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe presence of antibodies against domain I of β2-GPI and "triple positivity" were more frequent in patients who had a history of thrombosis.
“Specifically, we could observe that the presence of antibodies against domain I of β2-GPI and “triple positivity” were more frequent in patients who had a history of thrombosis.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
FindingreasoningThe relative contribution of diabetes towards thrombotic risk, as compared to smoking status and the lupus-sensitive aPTT, would have led to an uneven point score of 1.6 for diabetes, which was rounded to 2.
“In detail, the relative contribution of diabetes towards thrombotic risk, as compared to smoking status and the lupus-sensitive aPTT, would have led to an uneven point score of 1.6 for diabetes, which was rounded to 2.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIn vitro, interference by aPL autoantibodies with the clotting cascade is reflected in prolongation of phospholipid-dependent clotting assays, such as the activated partial thromboplastin time (aPTT).
“In vitro, the interference by these autoantibodies with the clotting cascade is reflected in the prolongation of phospholipid-dependent clotting assays, such as the activated partial thromboplastin time (aPTT) [2].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [2] Du VX, Kelchtermans H, de Groot PG, de Laat B. From antibody to clinical phenotype, the black box of the antiphospholipid syndrome: pathogenic mechanisms of the antiphospholipid syndrome. Thromb Res. 2013;132(3):319–26. source
May combine two claims.
Study design and conductown dataInternal validation procedures showed that the risk stratification rule featured a high discriminative performance and was well calibrated for prediction of 10-year thrombotic risk.
“Internal validation procedures showed that this risk stratification rule featured a high discriminative performance and was well calibrated for prediction of 10-year thrombotic risk.”
- Also stated in: § Thrombosis risk stratification in patients with LA · boosted
“Internal validation procedures showed a strong discrimination according to this point-based rule (Harrell’s C: 0.72), and calibration was excellent for 10-year thrombotic risk and moderate for 5-year thrombotic risk (Additional file 13: Figure S4).”
Quote in the paperSubstantial claim- Also stated in: § Thrombosis risk stratification in patients with LA · boosted
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThis sensitivity analysis has very low power.
“Although this analysis has very low power, it illustrates a differential pathobiology of these three risk factors.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataLong-term thrombotic risk in patients with LA is clustered within subjects harboring typical cardiovascular risk factors in addition to a prolonged lupus-sensitive aPTT, whereas patients with none of these risk factors represent a large subgroup with a low risk of thrombosis.
“Long-term thrombotic risk in patients with LA is clustered within subjects harboring typical cardiovascular risk factors in addition to a prolonged lupus-sensitive aPTT, whereas patients with none of these risk factors represent a large subgroup with a low risk of thrombosis.”
Quote in the paperSubstantial claim- Rests on an assumption: The associations between diabetes, smoking, prolonged lupus-sensitive aPTT and thrombotic risk are causal (these factors determine thrombotic risk).
- Rests on an assumption: The LATS cohort is representative of the broader population of patients with LA.
May combine two claims.
Interpretationown dataThe data support the concept that diabetes and active smoking may represent two factors for this "second-hit phenomenon" and that the adverse cardiovascular consequences of diabetes and smoking may lead to a deleterious thrombotic risk increase in patients with LA.
“Our data support the concept that diabetes and active smoking may represent two factors for this “second-hit phenomenon” and that the adverse cardiovascular consequences of diabetes and smoking may lead to a deleterious thrombotic risk increase in patients with LA.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenThe cohort features several strengths, including a stringent prospective design with a long follow-up, a small drop-out rate, and the time-dependent censoring of patients who became LA negative over time.
“Nevertheless, we would like to mention that our cohort features several strengths, including a stringent prospective design with a long follow-up, a small drop-out rate, and the time-dependent censoring of patients who became LA negative over time.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim. May combine two claims.
InterpretationreasoningThis must not be interpreted as an absence of efficacy, because reverse causality has likely confounded this observational result.
“Of course, this must not be interpreted as an absence of efficacy, because reverse causality has likely confounded this observational result.”
Quote in the paperSubstantial claimMay combine two claims.
Study design and conductown dataInternal validation procedures showed a strong discrimination according to the point-based rule (Harrell's C: 0.72), and calibration was excellent for 10-year thrombotic risk and moderate for 5-year thrombotic risk.
“Internal validation procedures showed a strong discrimination according to this point-based rule (Harrell’s C: 0.72), and calibration was excellent for 10-year thrombotic risk and moderate for 5-year thrombotic risk (Additional file 13: Figure S4).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductreasoningThe suggested risk stratification rule has some loss of information as compared to the full multivariable model, which is attributable to "rounding" of regression coefficients to a point-based system.
“Fourth, our suggested risk stratification rule has some loss of information as compared to the full multivariable model, which is attributable to “rounding” of regression coefficients to a point-based system.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
The associations between diabetes, smoking, prolonged lupus-sensitive aPTT and thrombotic risk are causal (these factors determine thrombotic risk).
“Cardiovascular risk factors are major determinants of thrombotic risk in patients with the lupus anticoagulant”
The paper relies on this without support.
The LATS cohort is representative of the broader population of patients with LA.
“Long-term thrombotic risk in patients with LA is clustered within subjects harboring typical cardiovascular risk factors in addition to a prolonged lupus-sensitive aPTT, whereas patients with none of these risk factors represent a large subgroup with a low risk of thrombosis.”
The paper relies on this without support.
The composite endpoint of arterial and venous thrombosis is a valid single outcome for risk stratification.
“The primary endpoint of the study is a composite of symptomatic, objectively confirmed arterial and/or venous thrombosis.”
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.
Domain I antibody missing-data percentage is too high
MinorWith 144 measurements among 150 patients, six are missing. That is 4.0% of the cohort, not the reported 6.0%.
Reported 6 · recomputed 4
“| Domain I abs (CU) | 144 (6.0%) | 30.3 [2.5-256.0] | 64.3 [4.1-498.2] | 5.9 [1.5-59.9] | 0.002 | 30.8 [3.2-245.3] | 24.8 [1.5-265.4] | 0.580 |”
Age hazard ratio falls outside its confidence interval
MinorTable 3 gives an adjusted age hazard ratio of 1.07, but its reported 95% confidence interval ends at 1.04.
“| Age at entry (per 5 years increase) | 1.06 | 0.97-1.17 | 0.193 | 1.07 | 0.99-1.04 | 0.174 |”
“1.07 | 0.99-1.04”
Risk-group event rates are labeled 5-year and 10-year risks
MinorThe abstract calls the three risk-group rates 5-year risks, but the Results section identifies the same rates for the same group sizes as 10-year risks.
“5-year TE risk of 9.7% (n = 77), 30.9% (n = 51), and 56.8% (n = 22)”
“10-year risk of TE in patients with 0 (n = 77), 1 (n = 51), or ≥2 (n = 22) points: 9.7%, 30.9%, and 56.8%, respectively”
Discussion reverses the protein Z IgM finding
MinorThe discussion says higher protein Z IgM was associated with a history of thrombosis. Table 1 instead shows a lower median in patients with prior thrombosis than in those without (5.5 versus 6.3), with p = 0.210.
“we only observed a weak association between higher IgM-isotype antibodies against protein Z and a higher risk of anamnestic thrombosis.”
“| Anti-protein Z IgM | 144 (4.0%) | 6.0 [4.1-9.1] | 5.5 [3.8-8.8] | 6.3 [4.6-9.6] | 0.210 |”
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“Differences in thrombosis incidence functions between two or more groups were investigated using Gray’s test [24].”
MethodInfluentialMIYAKIS, S., LOCKSHIN, M. D., ATSUMI, T., BRANCH, D. W., BREY, R. L., CERVERA, R., DERKSEN, R. H. W. M., DE GROOT, P. G., KOIKE, T., MERONI, P. L., et al. (2006) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2006.01753.x · Cited by 7,203 · cited 19× · see citing works
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BackgroundMethodInfluentialA Class of $K$-Sample Tests for Comparing the Cumulative Incidence of a Competing Risk
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“with LA is associated with an excessive increase in the risk of death, which in turn leads to a significantly impaired relative survival of these patients in comparison to an age- and sex-matched reference population [5, 6].”
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“5 s)), diabetes, smoking, and aCL IgM antibodies) was applied to construct a multivariable model for the prediction of thrombotic risk [26].”
MethodCollins, G. S., Reitsma, J. B., Altman, D. G., & Moons, K. G. M. (2015) · Circulation · doi:10.1161/circulationaha.114.014508 · Cited by 793 · see citing works
FINAZZI, G., MARCHIOLI, R., BRANCACCIO, V., SCHINCO, P., WISLOFF, F., MUSIAL, J., BAUDO, F., BERRETTINI, M., Testa, S., D'ANGELO, A., et al. (2005) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2005.01340.x · Cited by 585 · cited 1× · see citing works
“3% compares well to the thrombotic risk observed in the WAPS study [31] and the very large Euro-Phospholipid Project registry [6], but was lower than the value in the recently published Piedmont cohort study [32] and higher than that in the recently published study by Pengo et al.”
ResultCumulative Incidence Estimation in the Presence of Competing Risks
Coviello, V., & Boggess, M. M. (2004) · The Stata Journal Promoting communications on statistics and Stata · doi:10.1177/1536867x0400400201 · Cited by 463 · cited 1× · see citing works
“The cumulative incidence of the primary endpoint was calculated with cumulative incidence estimators according to Marubini and Valsecchi, treating death from any cause as a competing risk [23].”
MethodUrbanus, R. T., Siegerink, B., Roest, M., Rosendaal, F. R., de Groot, P. G., & Algra, A. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70239-x · Cited by 429 · see citing works
GAPSS: the Global Anti-Phospholipid Syndrome Score
Sciascia, S., Sanna, G., Murru, V., Roccatello, D., Khamashta, M. A., & Bertolaccini, M. L. (2013) · Rheumatology · doi:10.1093/rheumatology/kes388 · Cited by 318 · cited 2× · see citing works
“Consequently, our results are not directly generalizable to other patient groups included in the wide and heterogenic spectrum of APS, such as patients with SLE [34, 38] or patients who are positive for aCL or aβ2-GPI but not LA [39].”
BackgroundResultDE LAAT, B., PENGO, V., PABINGER, I., MUSIAL, J., VOSKUYL, A. E., BULTINK, I. E. M., RUFFATTI, A., ROZMAN, B., KVEDER, T., DE MOERLOOSE, P., et al. (2009) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2009.03588.x · Cited by 291 · cited 18× · see citing works
“Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, de Groot PG, Koike T, Meroni PL, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS).”
ResultInfluentialSelf-citationde Laat, H. B., Derksen, R. H. W. M., Urbanus, R. T., Roest, M., & de Groot, P. G. (2004) · Blood · doi:10.1182/blood-2004-03-1107 · Cited by 219 · cited 19× · see citing works
“Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, de Groot PG, Koike T, Meroni PL, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS).”
ResultInfluentialLupus anticoagulants and the risk of a first episode of deep venous thrombosis
DE GROOT, P. G., LUTTERS, B., DERKSEN, R. H. W. M., LISMAN, T., MEIJERS, J. C. M., & ROSENDAAL, F. R. (2005) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2005.01485.x · Cited by 205 · cited 1× · see citing works
“Background Autoantibodies directed against phospholipid-binding plasma proteins (also known as antiphospholipid (aPL) antibodies), detected through coagulation assays such as the lupus anticoagulant (LA) and through immunoassays such as anticardiolipin (aCL) or anti-β2-glycoprotein I (aβ2-GPI), confer an increased ris…”
BackgroundDetection and Quantitative Evaluation of Lupus Circulating Anticoagulant Activity
Rosner, E., Pauzner, R., Lusky, A., Modan, M., & Many, A. (1987) · Thrombosis and Haemostasis · doi:10.1055/s-0038-1651083 · Cited by 188 · cited 1× · see citing works
“In case of a not definitely positive confirmatory test during the follow-up period, LA was still regarded as positive if the Rosner Index, calculated as 100 × (clotting times of the 1:1 mixture - normal plasma)/patient’s plasma, was higher than 15 [20].”
MethodReynaud, Q., Lega, J.-C., Mismetti, P., Chapelle, C., Wahl, D., Cathébras, P., & Laporte, S. (2014) · Autoimmunity Reviews · doi:10.1016/j.autrev.2013.11.004 · Cited by 179 · see citing works
Galli, M., Borrelli, G., Jacobsen, E. M., Marfisi, R. M., Finazzi, G., Marchioli, R., Wisloff, F., Marziali, S., Morboeuf, O., & Barbui, T. (2007) · Blood · doi:10.1182/blood-2007-01-066043 · Cited by 170 · cited 2× · see citing works
“Further, a considerable proportion of patients with LA will not develop thrombosis despite the presence of aPL-associated autoantibodies at high titers [7].”
BackgroundDerksen, R. H. W. M., Hasselaar, P., Blokzijl, L., Gmelig-Meyling, F. H. J., & de Groot, P. G. (1988) · Annals of the Rheumatic Diseases · doi:10.1136/ard.47.5.364 · Cited by 138 · cited 1× · see citing works
“This hypothesis is supported by previous case-control studies that have implicated the length of a lupus-sensitive aPTT with thrombosis in LA [13, 36, 37].”
ResultPengo, V., Ruffatti, A., Tonello, M., Cuffaro, S., Banzato, A., Bison, E., Denas, G., & Padayattil Jose, S. (2015) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.12865 · Cited by 126 · cited 19× · see citing works
“Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, de Groot PG, Koike T, Meroni PL, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS).”
MethodResultInfluentialSelf-citationAntiphospholipid syndrome: multiple mechanisms
MACKWORTH-YOUNG, C. G. (2004) · Clinical and Experimental Immunology · doi:10.1111/j.1365-2249.2004.02497.x · Cited by 114 · cited 1× · see citing works
“Second, preclinical evidence from animal models has demonstrated that the presence of LA-related autoantibodies alone is insufficient for causing overt thrombosis, and a “second hit” such as inflammation or infection may be necessary to transform the prothrombotic potential induced by LArelated autoantibodies into ove…”
BackgroundThe global anti-phospholipid syndrome score in primary APS
Sciascia, S., Sanna, G., Murru, V., Roccatello, D., Khamashta, M. A., & Bertolaccini, M. L. (2015) · Rheumatology · doi:10.1093/rheumatology/keu307 · Cited by 107 · see citing works
Devreese, K., Peerlinck, K., & Hoylaerts, M. F. (2010) · Blood · doi:10.1182/blood-2009-09-244426 · Cited by 93 · see citing works
Incidence of a first thromboembolic event in carriers of isolated lupus anticoagulant
Pengo, V., Testa, S., Martinelli, I., Ghirarduzzi, A., Legnani, C., Gresele, P., Passamonti, S. M., Bison, E., Denas, G., Jose, S. P., et al. (2015) · Thrombosis Research · doi:10.1016/j.thromres.2014.10.013 · Cited by 89 · cited 19× · see citing works
“Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, de Groot PG, Koike T, Meroni PL, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS).”
BackgroundResultInfluentialSelf-citationGebhart, J., Posch, F., Koder, S., Perkmann, T., Quehenberger, P., Zoghlami, C., Ay, C., & Pabinger, I. (2015) · Blood · doi:10.1182/blood-2014-11-611129 · Cited by 72 · cited 3× · see citing works
“with LA is associated with an excessive increase in the risk of death, which in turn leads to a significantly impaired relative survival of these patients in comparison to an age- and sex-matched reference population [5, 6].”
BackgroundResultSelf-citationSciascia, S., Murru, V., Garcia-Fernandez, C., Sanna, G., Khamashta, M., & Bertolaccini, M. L. (2013) · Thrombosis and Haemostasis · doi:10.1160/th12-07-0527 · Cited by 67 · cited 1× · see citing works
“Among non-canonical aPL-associated antibodies [11], such as antibodies against protein Z or prothrombin, we only observed a weak association between higher IgM-isotype antibodies against protein Z and a higher risk of anamnestic thrombosis.”
BackgroundWenzel, C., Stoiser, B., Locker, G. J., et al. (2002) · Critical Care Medicine · doi:10.1097/00003246-200204000-00007 · Cited by 66 · cited 1× · see citing works
“in the case of prolongation of one or both screening tests [19].”
BackgroundSelf-citationRand, J., Xx, W., Quinn, A., & Taatjes, D. J. (2008) · Lupus · doi:10.1177/0961203308095029 · Cited by 62 · cited 1× · see citing works
“The annexin A5 resistance ratio (A5R) was measured as previously described, expressed as the ratio of in vitro coagulation times with and without annexin A5 [21].”
MethodSelf-citationBazzan, M., Vaccarino, A., Stella, S., Sciascia, S., Montaruli, B., Bertero, M. T., Carignola, R., Roccatello, D., & for the Piedmont APS Consortium (2016) · Lupus · doi:10.1177/0961203315617538 · Cited by 56 · see citing works
Sciascia, S., Cuadrado, M. J., Sanna, G., Murru, V., Roccatello, D., Khamashta, M. A., & Bertolaccini, M. L. (2014) · Arthritis Care & Research · doi:10.1002/acr.22388 · Cited by 55 · cited 2× · see citing works
“Further, a risk score for anamnestic thrombotic risk in patients with SLE, the Global Anti-Phospholipid Syndrome Score (GAPSS), includes two general cardiovascular risk factors: hypertension and hyperlipidemia [34].”
ResultThe antiphospholipid syndrome: still an enigma
Chaturvedi, S., & McCrae, K. R. (2015) · Hematology · doi:10.1182/asheducation-2015.1.53 · Cited by 51 · see citing works
Pengo, V., Ruffatti, A., Tonello, M., Hoxha, A., Bison, E., Denas, G., Padayattil Jose, S., Zoppellaro, G., Bracco, A., & Banzato, A. (2015) · Thrombosis Research · doi:10.1016/j.thromres.2015.04.031 · Cited by 47 · cited 18× · see citing works
“Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, de Groot PG, Koike T, Meroni PL, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS).”
ResultInfluentialSelf-citationDu, V. X., Kelchtermans, H., de Groot, P. G., & de Laat, B. (2013) · Thrombosis Research · doi:10.1016/j.thromres.2013.07.023 · Cited by 35 · cited 1× · see citing works
“In vitro, the interference by these autoantibodies with the clotting cascade is reflected in the prolongation of phospholipid-dependent clotting assays, such as the activated partial thromboplastin time (aPTT) [2].”
Antiphospholipid Antibodies and Recurrent Thrombotic Events: Persistence and Portfolio
Amory, C. F., Levine, S. R., Brey, R. L., Gebregziabher, M., Tuhrim, S., Tilley, B. C., Simpson, A.-C. C., Sacco, R. L., Mohr, J. P., & Collaborators, F. T. A.-W. (2015) · Cerebrovascular Diseases · doi:10.1159/000441362 · Cited by 31 · cited 1× · see citing works
“triple positivity has been shown to be a significant thrombotic risk factor in the WAPS study [7], several more recent prospective cohorts have also observed a lack of association between triple positivity or other LArelated autoantibodies and thrombosis [30, 32, 33].”
BackgroundPathogenesis of the antiphospholipid syndrome revisited: time to challenge the dogma
Lackner, K. J., & Müller‐Calleja, N. (2016) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.13320 · Cited by 24 · cited 1× · see citing works
“These results confirm and validate several previous reports that have implicated these antibodies in the pathogenesis of APS [9, 10, 12, 13, 29, 30], but they also add to the growing body of evidence that shows inconsistent associations between aPL-associated autoantibodies and anamnestic thrombotic risk [3, 16].”
ResultChen, J., Sun, S., Yan, Q., Bao, C., & Fu, Q. (2016) · Clinical Rheumatology · doi:10.1007/s10067-015-3159-8 · Cited by 12 · cited 1× · see citing works
“This hypothesis is supported by previous case-control studies that have implicated the length of a lupus-sensitive aPTT with thrombosis in LA [13, 36, 37].”
Result
Flagged first, then by citations
Cited by
Sorted by citations
Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome
Pengo, V., Denas, G., Zoppellaro, G., Jose, S. P., Hoxha, A., Ruffatti, A., Andreoli, L., Tincani, A., Cenci, C., Prisco, D., et al. (2018) · Blood · doi:10.1182/blood-2018-04-848333 · Cited by 822 · see citing works
“Medications at time of randomization, n (%) Hydroxychloroquine 15 (25) 23 (38) Corticosteroids 11 (19) 13 (21) Other immunosuppressive drugs 17 (29) 21 (34)”
BackgroundSelf-citationÜnlü, O., Erkan, D., Barbhaiya, M., ANDRADE, D. C. O. D., Nascimento, I. S., Rosa, R. F., Banzato, A., Pengo, V., Ugarte, A., Gerosa, M., et al. (2018) · Arthritis Care & Research · doi:10.1002/acr.23584 · Cited by 60 · see citing works
“6) Reported as “other” 12 (2) 9 (2) 3 (2) Ethnicity‡ US, Canada, Europe 261 (51) 183 (50) 78 (55) Non–Latin American 242 (48) 168 (46) 74 (48) Latin American 19 (4) 15 (4) 4 (3) South America 124 (24) 96 (26) 28 (20) Afrodescendant 16 (3) 8 (2) 8 (6) Mestizo 67 (13) 54 (15) 13 (9) Caucasian 41 (8) 34 (9) 7 (5) Austral…”
BackgroundInfluentialSelf-citationLupus Anticoagulant Identifies Two Distinct Groups of Patients with Different Antibody Patterns
Pengo, V., Del Ross, T., Ruffatti, A., Bison, E., Cattini, M. G., Pontara, E., Testa, S., Legnani, C., Pozzi, N., Peterle, D., et al. (2018) · Thrombosis Research · doi:10.1016/j.thromres.2018.11.003 · Cited by 59 · see citing works
Self-citationMinno, M. N. D. D., Scalera, A., Tufano, A., Ambrosino, P., Bettiol, A., Silvestri, E., Emmi, G., & Prisco, D. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.09.010 · Cited by 48 · see citing works
An Update on Antiphospholipid Syndrome
Xourgia, E., & Tektonidou, M. G. (2021) · Current Rheumatology Reports · doi:10.1007/s11926-021-01051-5 · Cited by 50 · see citing works
Mauracher, L., Krall, M., Roiß, J., Hell, L., Koder, S., Hofbauer, T. M., Gebhart, J., Hayden, H., Brostjan, C., Ay, C., et al. (2020) · Lara D. Veeken · doi:10.1093/rheumatology/keaa532 · Cited by 31 · see citing works
Self-citationHigh risk of adverse pregnancy outcomes in women with a persistent lupus anticoagulant
Gebhart, J., Posch, F., Koder, S., Quehenberger, P., Perkmann, T., Kuessel, L., Ay, C., & Pabinger, I. (2019) · Blood Advances · doi:10.1182/bloodadvances.2018026948 · Cited by 29 · see citing works
“The calculated birth weight percentiles by gestational age were lower but not significantly different between these 2 groups (21 [10-45] and 32 [21-58], P 5 .”
BackgroundSelf-citationJiang, H., Wang, C.-H., Jiang, N., Li, J., Wu, C., Wang, Q., Li, M., Tian, X., Zhao, J., Zhao, Y., et al. (2021) · Arthritis Research & Therapy · doi:10.1186/s13075-021-02515-w · Cited by 27 · see citing works
Hell, L., Lurger, K., Mauracher, L., Grilz, E., Reumiller, C. M., Schmidt, G. J., Ercan, H., Koder, S., Assinger, A., Basílio, J., et al. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-019-0358-4 · Cited by 27 · see citing works
Self-citationZuo, Y., Barbhaiya, M., & Erkan, D. (2018) · Current Rheumatology Reports · doi:10.1007/s11926-018-0775-8 · Cited by 24 · see citing works
“Posch, 2017 [46••] Prospective observational cohort 150 LA-positive patients (included patients who had prior thrombosis and pregnancy morbidities) Diabetes (HR = 3.97, 95% CI 1.29–12.19), smoking (HR= 2.42, 95% CI 1.15–5.06), and prolonged aPTT (HR = 2.28, 95% CI 1.04–4.99) were independent…”
BackgroundInfluentialPrimary thromboprophylaxis with low-dose aspirin and antiphospholipid antibodies: Pro's and Con's
Arnaud, L., Conti, F., Massaro, L., Denas, G., Chasset, F., & Pengo, V. (2017) · Autoimmunity Reviews · doi:10.1016/j.autrev.2017.09.003 · Cited by 16 · see citing works
Self-citationYue, Y., Sun, Q., Man, G. C. W., & Fu, Y. (2018) · Clinical and Experimental Medicine · doi:10.1007/s10238-018-0529-y · Cited by 15 · see citing works
Hell, L., Ay, C., Posch, F., Gebhart, J., Koder, S., Mackman, N., Pabinger, I., & Thaler, J. (2018) · Annals of Hematology · doi:10.1007/s00277-018-3544-x · Cited by 15 · see citing works
Self-citationHinojosa, C. A., Anaya‐Ayala, J. E., Bermúdez-Serrato, K., et al. (2017) · Vascular and Endovascular Surgery · doi:10.1177/1538574417729273 · Cited by 13 · see citing works
Peleg, H., Naparstek, Y., Regola, F., Tincani, A., Pengo, V., & Denas, G. (2019) · Autoimmunity Reviews · doi:10.1016/j.autrev.2019.102408 · Cited by 9 · see citing works
Self-citationSchulz, A., Herrmann, E. M., Ott, O., & Lindhoff‐Last, E. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11164845 · Cited by 8 · see citing works
“In APS patients with venous thrombosis, the results of this registry suggest that physicians can consider DOAC treatment in non-triple-positive APS patients on a case-bycase basis, taking into account the presence of additional risk factors for venous and arterial thrombosis [32] and the risk for bleeding [8].”
Zuo, Y., Fan, J., Sarode, R., Zhang, S., Makris, U. E., Karp, D. R., & Shen, Y.-M. (2018) · Clinical and Applied Thrombosis/Hemostasis · doi:10.1177/1076029618755946 · Cited by 7 · see citing works
“A recent prospective study of thrombotic risk among 150 LA-positive patients did not show an association between HTN and thrombosis.(22) Our study demonstrates that HTN is an independent risk factor for arterial thrombosis among ethnically diverse aPL carriers.”
BackgroundFrom arteries to veins: the expanding role of lipid-lowering drugs in preventing thrombosis
Nopp, S., Ay, C., & Pabinger, I. (2024) · European Heart Journal · doi:10.1093/eurheartj/ehae492 · Cited by 6 · see citing works
Self-citationLupus anticoagulant test persistence over time and its associations with future thrombotic events
Colling, M. E., Ay, C., Kraemmer, D., Koder, S., Quehenberger, P., Pabinger, I., Posch, F., & Gebhart, J. (2022) · Blood Advances · doi:10.1182/bloodadvances.2021006011 · Cited by 5 · see citing works
“This corresponded to 10-year prospective ATE, VTE, and overall thrombosis incidences of 14% (95%CI: 9-21), 20% (13-28), and 34% (26-43), respectively, and a 10-year mortality of 14% (9-22) (supplemental Figure 2).”
BackgroundSelf-citationPengo, V., Sarti, L., Antonucci, E., Bison, E., Pontara, E., Cattini, M. G., Denas, G., Poli, D., & Palareti, G. (2024) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2024-0114 · Cited by 2 · see citing works
“These data underpin the hypothesis that cardiovascular risk factors rather than the hypercoagulable state induced by aPL are major determinants of arterial thrombosis in APS [25].”
BackgroundSelf-citationAndrade-Ortega, L., Xibille-Friedmann, D. X., Galarza-Delgado, D. Á., Saavedra, M. Á., Álvarez-Nemegyei, J., Castañeda, M. C. A., Fragoso-Loyo, H. E., Gordillo-Huerta, M. V., Irazoque-Palazuelos, F. C., Jara-Quezada, L. J., et al. (2024) · Reumatología Clínica · doi:10.1016/j.reuma.2024.07.004 · Cited by 2 · see citing works
Martín-Portugués, I. A., Sánchez-Mesa, B., & Lora, F. J. S. (2017) · Medicine - Programa de Formación Médica Continuada Acreditado · doi:10.1016/j.med.2017.10.004 · Cited by 2 · see citing works
Clinical Practice Mexican Guidelines for the Treatment of Systemic Lupus Erythematosus: 2024 Update
Andrade-Ortega, L., Xibille-Friedmann, D. X., Galarza-Delgado, D. Á., Saavedra, M. Á., Álvarez-Nemegyei, J., Castañeda, M. C. A., Fragoso-Loyo, H. E., Gordillo-Huerta, M. V., Irazoque-Palazuelos, F. C., Jara-Quezada, L. J., et al. (2024) · Reumatología Clínica (English Edition) · doi:10.1016/j.reumae.2024.10.003 · Cited by 1 · see citing works
Oral anticoagulants in thrombotic antiphospholipid syndrome: Leave the old road for a new trail?
Pengo, V. (2020) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2020.07.020 · Cited by 1 · see citing works
Self-citationObeidat, O., Alhuneafat, L., Ismail, M. F., et al. (2026) · The American Journal of the Medical Sciences · doi:10.1016/j.amjms.2026.08.019
- Authors
- Posch, F., Gebhart, J., Rand, J. H., Koder, S., Quehenberger, P., Pengo, V., Ay, C., & Pabinger, I.
- Affiliations
- Medical University of Graz (AT)
- Comprehensive Cancer Center Vienna (AT)
- Weill Cornell Medicine (US)
- Medical University of Vienna (AT)
- University of Padua (IT)
- Corresponding author
- Pabinger, Ingrid
- ORCID
- Venue
- BMC Medicine
- Published
- 2017-03-10
- Volume
- 15
- Issue
- 1
- Pages
- 54-54
- ISSN
- 1741-7015 (ISSN-L)
- PMC
- PMC5345189
- OpenAlex
- W2593137415
- Cited by
- 25
- References
- 41
- Citations by year
- 2026: 1 · 2024: 4 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 8 · 2017: 3
- FWCI
- 3.36
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Medicine (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by)
- Funders
- Austrian Science Fund (AT) (SFB-54)
- 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, cardiovascular risk factors, diabetes mellitus, smoking, arterial thrombosis, venous thrombosis, risk stratification
- MeSH terms
- Adult, Cardiovascular Diseases, Female, Humans, Male, Middle Aged, Risk Factors
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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.
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