Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Medicine
Published in: BMC Medicine 1/2017

Open Access 01-12-2017 | Research article

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

Authors: Florian Posch, Johanna Gebhart, Jacob H. Rand, Silvia Koder, Peter Quehenberger, Vittorio Pengo, Cihan Ay, Ingrid Pabinger

Published in: BMC Medicine | Issue 1/2017

Login to get access

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.
Appendix
Available only for authorised users
Literature
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.CrossRefPubMed
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.CrossRefPubMed
3.
Chaturvedi S, McCrae KR. The antiphospholipid syndrome: still an enigma. Hematology Am Soc Hematol Educ Program. 2015;2015(1):53–60.PubMedPubMedCentral
4.
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). J Thromb Haemost. 2006;4(2):295–306.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
8.
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
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
14.
Devreese K, Peerlinck K, Hoylaerts MF. Thrombotic risk assessment in the antiphospholipid syndrome requires more than the quantification of lupus anticoagulants. Blood. 2010;115(4):870–8.CrossRefPubMed
15.
Urbanus RT, Siegerink B, Roest M, Rosendaal FR, de Groot PG, Algra A. Antiphospholipid antibodies and risk of myocardial infarction and ischaemic stroke in young women in the RATIO study: a case-control study. Lancet Neurol. 2009;8(11):998–1005.CrossRefPubMed
16.
Lackner KJ, Muller-Calleja N. Pathogenesis of the antiphospholipid syndrome revisited — time to challenge the dogma. J Thromb Haemost. 2016.
17.
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
18.
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
19.
Wenzel C, Stoiser B, Locker GJ, Laczika K, Quehenberger P, Kapiotis S, Frass M, Pabinger I, Knobl P. Frequent development of lupus anticoagulants in critically ill patients treated under intensive care conditions. Crit Care Med. 2002;30(4):763–70.CrossRefPubMed
20.
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
21.
Rand JH, Wu XX, Quinn AS, Taatjes DJ. Resistance to annexin A5 anticoagulant activity: a thrombogenic mechanism for the antiphospholipid syndrome. Lupus. 2008;17(10):922–30.CrossRefPubMed
22.
Schemper M, Smith TL. A note on quantifying follow-up in studies of failure time. Control Clin Trials. 1996;17(4):343–6.CrossRefPubMed
23.
Coviello V, Boggess M. Cumulative incidence estimation in the presence of competing risks. Stata J. 2004;4(2):103–12.
24.
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
25.
Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.CrossRef
26.
Moons KG, Kengne AP, Woodward M, Royston P, Vergouwe Y, Altman DG, Grobbee DE. Risk prediction models: I. Development, internal validation, and assessing the incremental value of a new (bio)marker. Heart. 2012;98(9):683–90.CrossRefPubMed
27.
Royston P, Moons KG, Altman DG, Vergouwe Y. Prognosis and prognostic research: Developing a prognostic model. BMJ. 2009;338:b604.CrossRefPubMed
28.
Collins GS, Reitsma JB, Altman DG, Moons KG. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement. The TRIPOD Group. Circulation. 2015;131(2):211–9.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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​
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.CrossRefPubMedPubMedCentral
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.CrossRef
35.
36.
Derksen RH, Hasselaar P, Blokzijl L, Gmelig Meyling FH, de Groot PG. Coagulation screen is more specific than the anticardiolipin antibody ELISA in defining a thrombotic subset of lupus patients. Ann Rheum Dis. 1988;47(5):364–71.CrossRefPubMedPubMedCentral
37.
Chen J, Sun S, Yan Q, Bao C, Fu Q. Elevated partial antiphospholipid score is a strong risk factor for thrombosis in patients with systemic lupus erythematosus: a validation study. Clin Rheumatol. 2016;35(2):333–40.CrossRefPubMed
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.CrossRef
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.CrossRef
Metadata
Title
Cardiovascular risk factors are major determinants of thrombotic risk in patients with the lupus anticoagulant
Authors
Florian Posch
Johanna Gebhart
Jacob H. Rand
Silvia Koder
Peter Quehenberger
Vittorio Pengo
Cihan Ay
Ingrid Pabinger
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2017
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-017-0807-7

Other articles of this Issue 1/2017

BMC Medicine 1/2017 Go to the issue

Research article

RETRACTED ARTICLE:The impact of repeated vaccination on influenza vaccine effectiveness: a systematic review and meta-analysis

Research article

Risk and predictors of psoriasis in patients with breast cancer: a Swedish population-based cohort study

Review

The renin–angiotensin system: a possible new target for depression

Research article

Factors associated with junior doctors’ decisions to apply for general practice training programmes in the UK: secondary analysis of data from the UKMED project

Guideline

DIET@NET: Best Practice Guidelines for dietary assessment in health research

Research article

Health-related quality of life and psychological distress among cancer survivors in Southeast Asia: results from a longitudinal study in eight low- and middle-income countries