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01.12.2017 | Research article | Ausgabe 1/2017 Open Access

BMC Medicine 1/2017

Cardiovascular risk factors are major determinants of thrombotic risk in patients with the lupus anticoagulant

Zeitschrift:
BMC Medicine > Ausgabe 1/2017
Autoren:
Florian Posch, Johanna Gebhart, Jacob H. Rand, Silvia Koder, Peter Quehenberger, Vittorio Pengo, Cihan Ay, Ingrid Pabinger
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s12916-017-0807-7) contains supplementary material, which is available to authorized users.

Abstract

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.
Zusatzmaterial
Additional file 1: Paragraph 1. Study design and endpoint. (DOCX 85 kb)
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Additional file 2: Paragraph 2. Sample preparation. (DOCX 60 kb)
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Additional file 3: Paragraph 3. Statistical methods. (DOCX 132 kb)
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Additional file 4: Table S1. Models for predicting arterial events only and venous events only. (DOCX 17 kb)
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Additional file 5: Table S2. Spearman’s correlation coefficient (p value) between selected LA-related antibodies as well as selected “non-canonical” antibodies for the antiphospholipid syndrome. (DOCX 19 kb)
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Additional file 6: Table S3. Distribution of selected hemostatic parameters according to treatment with oral anticoagulation status at baseline. (DOCX 17 kb)
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Additional file 7: Table S4. Baseline characteristics of the study cohort according to prior history of pregnancy complications. (DOCX 25 kb)
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Additional file 8 Figure S1. Cumulative incidence of thrombosis in the total study cohort. (DOCX 23 kb)
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Additional file 9: Figure S2. Thrombotic risk according to baseline presence of diabetes (A), smoking (B), and a prolonged lupus-sensitive aPTT (C). (DOCX 36 kb)
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Additional file 10: Figure S3. Thrombotic risk according to baseline presence of established APS. (DOCX 36 kb)
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Additional file 11: Table S5. Multivariable models for thrombotic risk in LA patients adjusted for oral anticoagulation at baseline. (DOCX 17 kb)
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Additional file 12: Paragraph 4. Sensitivity analyses for developing the point-based thrombotic risk scoring system. (DOCX 21 kb)
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Additional file 13: Figure S4. Calibration bar graph of the proposed empirical risk stratification rule. (DOCX 22 kb)
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