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SAT0203 SINGLE LAC POSITIVITY VERSUS DOUBLE AND TRIPLE POSITIVITY FOR THROMBOSIS IN SLE
Open accessAbstract
The antiphospholipid syndrome (APS) is defined by the development of venous and/or arterial thromboses, and pregnancy morbidity, in the presence of antiphospholipid antibodies (aPL); lupus anticoagulant, moderate-to-high titer anticardiolipin (aCL) and anti-β2-glycoprotein (aB2GPI). It has been suggested that the incidence of thromboembolic events were significantly higher in the triple positive subjects, and the rate of pregnancy loss was also significantly much higher in double positive subjects (1). On the other hand several studies showed that LAC is more highly associated with thrombosis risk (2).We aimed to investigate the risk of thrombosis in Systemic Lupus Erythematosus (SLE) patients with single LAC positivity versus double and triple positivity in Hopkins Lupus Cohort.The Hopkins Lupus Cohort is a prospective longitudinal cohort of SLE patients ongoing since 1987. This analysis was based on cohort experience from 2003 through October 2019. Anticardiolipin and anti-Beta2 glycoprotein were defined as positive when the antibody titer exceeded 20 units. The lupus anticoagulant was determined by dilute Russell’s viper venom time (dRVVT) and confirmatory mixing studies, if prolonged. It is defined as positive if a patient had a dRVVT of 45 or more second and a positive confirm ratio of more than 1.4. For each aPL, we defined the patient as positive at a given month of follow up if they ever had a positivity in previous measures. The relationships between thrombosis and aPL were adjusted for number of prior aPL assessment.There were 805 patients with a complete profile of 7 antiphospholipid antibodies, with a total of 73417 person months (6118 person years) of follow up. For any thrombosis when compared to patients with LAC positivity only, double positivity with any isotypes [1.15(0.50, 2.66) p=0.7484] and triple positivity with any isotypes [1.68(0.74, 3.80), p=0.2145] showed a higher point estimates but statistically not significant (Table 1).Table 1.Single, double and triple positive patterns and the risk of any thrombosis.PatternNumber of eventsPerson-yearsRate per 1000 person-yearsadjusted RR (95% CI)p-valueLAC positivity only1063315.81.00 (Ref)Never any aPL33258112,80.73(0.36, 1.47)0.3819any aCL positivity only67937,60.43(0.16, 1.18)0.1028any aB2GPI positivity only751713,50.78(0.30,2.05)0.6195any aCL and aB2GPI positivity only540412,40.71(0.24,2.04)0.5211LAC and ACL positivity740617,31.15(0.50,2.66)0.7484LAC and aB2GPI positivity1249024,5Triple positivity01470,01.68(0.74,3.80)0.2145We found that triple or double positive aPL profiles are not superior to single LAC positivity in their association with any thrombosis in SLE patients.[1]Pengo V, Ruffatti A, Del Ross T, Tonello M, Cuffaro S, Hoxha A, Banzato A,Bison E, Denas G, Bracco A, Padayattil Jose S. Confirmation of initial antiphospholipid antibody positivity depends on the antiphospholipid antibody profile. J Thromb Haemost. 2013 Aug;11(8):1527-31.[2]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.Selcan Demir: None declared, Jessica Li: None declared, Laurence Magder: None declared, Michelle A Petri Grant/research support from: GSK, Eli Lilly and Company, Consultant of: Eli Lilly and Company
Overview
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Written from the paper’s full text.
TL;DR
In the Hopkins Lupus Cohort, single LAC positivity was not inferior to double or triple antiphospholipid antibody positivity in its association with any thrombosis in SLE patients. Double and triple positivity showed higher point estimates but were not statistically significant.
Key findings
- Among 805 SLE patients with a complete profile of 7 antiphospholipid antibodies (73,417 person-months; 6,118 person-years), LAC-positivity-only had 10 thrombosis events (15.8 per 1,000 person-years) and served as the reference.
- Double positivity with any isotypes showed an adjusted RR of 1.15 (95% CI 0.50–2.66, p=0.7484) versus LAC-only; triple positivity with any isotypes showed an adjusted RR of 1.68 (95% CI 0.74–3.80, p=0.2145) — higher point estimates but not statistically significant.
- Triple positivity recorded 0 events over 147 person-years; never-any-aPL had 33 events over 2,581 person-years (RR 0.73, 95% CI 0.36–1.47, p=0.3819).
- The authors conclude that triple or double positive aPL profiles are not superior to single LAC positivity for association with any thrombosis in SLE.
Methods
- Prospective longitudinal cohort study (Hopkins Lupus Cohort, ongoing since 1987), based on cohort experience from 2003 through October 2019.
- Anticardiolipin and anti-β2-glycoprotein were defined as positive when titer exceeded 20 units; LAC was determined by dilute Russell's viper venom time (dRVVT) and confirmatory mixing studies, defined as positive with a dRVVT of ≥45 seconds and a confirm ratio >1.4.
- For each aPL, a patient was considered positive at a given follow-up month if they had ever been positive in previous measures; relationships between thrombosis and aPL were adjusted for number of prior aPL assessments.
Limitations
Not stated in the paper. Evident from the text: event counts are small (e.g., 10 events in the LAC-only group, 0 events in the triple-positive group), producing wide confidence intervals and precluding firm conclusions; the analysis is reported as a conference abstract with limited detail on adjustment and modeling.
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Claims the paper makes
- Findingown data
In SLE patients, triple or double positive aPL profiles are not superior to single LAC positivity in their association with any thrombosis.
“We found that triple or double positive aPL profiles are not superior to single LAC positivity in their association with any thrombosis in SLE patients.”
Quote in the paperSubstantial claim- Rests on an assumption: The Hopkins Lupus Cohort is representative of SLE patients generally.
- It may state two separate claims as one. 3
- Probably not a substantial claim. 2
It may state two separate claims as one.
Findingown dataAmong SLE patients in the Hopkins Lupus Cohort, compared with LAC positivity only, triple aPL positivity with any isotypes was associated with any thrombosis with an adjusted RR of 1.68 (95% CI 0.74-3.80), which was not statistically significant (p=0.2145).
“For any thrombosis when compared to patients with LAC positivity only, double positivity with any isotypes [1.15(0.50,2.66) p=0.7484] and triple positivity with any isotypes [1.68(0.74,3.80), p=0.2145] showed a higher point estimates but statistically not significant (Table 1).”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataAmong SLE patients in the Hopkins Lupus Cohort, compared with LAC positivity only, double aPL positivity with any isotypes was associated with any thrombosis with an adjusted RR of 1.15 (95% CI 0.50-2.66), which was not statistically significant (p=0.7484).
“For any thrombosis when compared to patients with LAC positivity only, double positivity with any isotypes [1.15(0.50,2.66) p=0.7484] and triple positivity with any isotypes [1.68(0.74,3.80), p=0.2145] showed a higher point estimates but statistically not significant (Table 1).”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataIn the Hopkins Lupus Cohort analysis, there were 805 SLE patients with a complete profile of 7 antiphospholipid antibodies, with a total of 73,417 person-months (6,118 person-years) of follow-up.
“There were 805 patients with a complete profile of 7 antiphospholipid antibodies, with a total of 73417 person months (6118 person years) of follow up.”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Study design and conductnone givenThe relationships between thrombosis and aPL were adjusted for number of prior aPL assessment.
“The relationships between thrombosis and aPL were adjusted for number of prior aPL assessment.”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Study design and conductnone givenThe Hopkins Lupus Cohort is a prospective longitudinal cohort of SLE patients ongoing since 1987.
“The Hopkins Lupus Cohort is a prospective longitudinal cohort of SLE patients ongoing since 1987.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
The Hopkins Lupus Cohort is representative of SLE patients generally.
“We found that triple or double positive aPL profiles are not superior to single LAC positivity in their association with any thrombosis in SLE patients.”
Citations
Cited by
Sorted by citations
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Muscat, S. N., Nichols, A. E. C., Gira, E., & Loiselle, A. E. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.07.20.500814 · Cited by 1
Metadata
- Authors
- Demir, S., Li, J., Magder, L., & Petri, M. A.
- Affiliations
- Johns Hopkins University (US)
- University of Maryland, Baltimore (US)
- Venue
- Annals of the Rheumatic Diseases
- Publisher
- Elsevier BV
- Published
- 2020-06
- Volume
- 79
- Pages
- 1044
- ISSN
- 0003-4967 (ISSN-L)
- OpenAlex
- W3123062432
- Semantic Scholar
- 367e3ba621c17f5d4c65161dc36071c258d78653
- Cited by
- 3
- References
- 0
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 1
- Type
- conference abstract
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annals of the Rheumatic Diseases (publishedVersion)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Rheumatology › Vasculitis and related conditions
- Keywords
- lupus anticoagulant, antiphospholipid syndrome, systemic lupus erythematosus, thrombosis risk, anticardiolipin antibodies, anti-beta2-glycoprotein I antibodies, triple positivity, dilute Russell's viper venom time, miscarriage, thromboembolism
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