The online version of this article (doi:10.1186/s12916-017-0807-7) contains supplementary material, which is available to authorized users.
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.
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).
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).
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.
Additional file 4: Table S1. Models for predicting arterial events only and venous events only. (DOCX 17 kb)
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)
Additional file 6: Table S3. Distribution of selected hemostatic parameters according to treatment with oral anticoagulation status at baseline. (DOCX 17 kb)
Additional file 7: Table S4. Baseline characteristics of the study cohort according to prior history of pregnancy complications. (DOCX 25 kb)
Additional file 8 Figure S1. Cumulative incidence of thrombosis in the total study cohort. (DOCX 23 kb)
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)
Additional file 10: Figure S3. Thrombotic risk according to baseline presence of established APS. (DOCX 36 kb)
Additional file 11: Table S5. Multivariable models for thrombotic risk in LA patients adjusted for oral anticoagulation at baseline. (DOCX 17 kb)
Additional file 12: Paragraph 4. Sensitivity analyses for developing the point-based thrombotic risk scoring system. (DOCX 21 kb)
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. CrossRefPubMed
Reynaud Q, Lega JC, Mismetti P, Chapelle C, Wahl D, Cathebras P, Laporte S. Risk of venous and arterial thrombosis according to type of antiphospholipid antibodies in adults without systemic lupus erythematosus: a systematic review and meta-analysis. Autoimmun Rev. 2014;13(6):595–608. CrossRefPubMed
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. CrossRefPubMed
Lackner KJ, Muller-Calleja N. Pathogenesis of the antiphospholipid syndrome revisited — time to challenge the dogma. J Thromb Haemost. 2016.
Brandt JT, Triplett DA, Alving B, Scharrer I. Criteria for the diagnosis of lupus anticoagulants: an update. On behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH. Thrombosis and haemostasis. 1995;74(4):1185–90. PubMed
Pengo V, Tripodi A, Reber G, Rand JH, Ortel TL, Galli M, de Groot PG. Update of the guidelines for lupus anticoagulant detection. Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost. 2009;7(10):1737–40. CrossRefPubMed
Rosner E, Pauzner R, Lusky A, Modan M, Many A. Detection and quantitative evaluation of lupus circulating anticoagulant activity. Thromb Haemost. 1987;57(2):144–7. PubMed
Coviello V, Boggess M. Cumulative incidence estimation in the presence of competing risks. Stata J. 2004;4(2):103–12.
Gray RJ. A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Statist. 1998;16(3):1141–54. CrossRef
Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509. CrossRef
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. CrossRefPubMed
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
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. CrossRef
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. CrossRef
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. CrossRef
- Cardiovascular risk factors are major determinants of thrombotic risk in patients with the lupus anticoagulant
Jacob H. Rand
- BioMed Central
Neu im Fachgebiet Allgemeinmedizin
Meistgelesene Bücher aus dem Fachgebiet
Mail Icon II