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

Abstract

BackgroundPatients 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.MethodsWe 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).ResultsDuring 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).ConclusionsLong-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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-017-0807-7) contains supplementary material, which is available to authorized users.

Low extracellular vesicle–associated tissue factor activity in patients with persistent lupus anticoagulant and a history of thrombosis

“…Consistent with this notion, during the observation period of our patients, smoking and diabetes were strong risk factors for developing thrombosis, which therefore represent two potential factors of the aforementioned “second hit phenomenon” [30]. Data from our study do not indicate that TF-bearing EVs contribute to this “second hit.” However, we cannot exclude a role of very low levels of TF-bearing EVs, which cannot be detected with our assay [22].…”

“…Data from experimental studies indicate that a “second prothrombotic hit” might be needed for the development of APS, because in mouse models, elevated antiphospholipid antibodies promoted thrombosis only in presence of vascular damage, endothelial activation, or inflammation [ 28 , 29 ]. Consistent with this notion, during the observation period of our patients, smoking and diabetes were strong risk factors for developing thrombosis, which therefore represent two potential factors of the aforementioned “second hit phenomenon” [ 30 ]. Data from our study do not indicate that TF-bearing EVs contribute to this “second hit.” However, we cannot exclude a role of very low levels of TF-bearing EVs, which cannot be detected with our assay [ 22 ].…”

The Impact of Systemic Lupus Erythematosus on the Clinical Phenotype of Antiphospholipid Antibody–Positive Patients: Results From the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Clinical Database and Repository

“…Traditional CVD risk factors, including diabetes and smoking, increase the risk of thrombosis in aPL-positive patients (20). Systemic lupus erythematosus itself is an independent risk factor for CVD, which still remains the major cause of mortality in SLE patients (21).…”

Altered platelet proteome in lupus anticoagulant (LA)-positive patients—protein disulfide isomerase and NETosis as new players in LA-related thrombosis

“…The Vienna Lupus Anticoagulant and Thrombosis Study is an ongoing, prospective, single-center cohort study enrolling adult patients persistently positive for LA (confirmed 12 weeks apart). Details on the study design have been elaborately described before 7,16 . In the current analysis, patients with a history of TE and patients without a history of TE who attended their regular follow-up visits between 2015 and 2017 were asked for new blood samples.…”

“…Nevertheless, not all individuals with LA develop TE 6 . Several other risk factors promoting thrombosis have been identified 7,8 . However, more specific biomarkers are needed to predict and treat individual thrombotic risk.…”