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.
Highlights
Patients with the lupus anticoagulant (LA) are at an increased risk of thrombotic events, which in turn increase the risk of death
A long lupus-sensitive activated partial thromboplastin time (aPTT) was significantly correlated with a higher level of IgG-isotype antibodies against domain I of β2-GPI and a lower prothrombin time
Based on our univariable findings and a prespecified model-building algorithm, we identified a simple empirical risk stratification rule including the variables diabetes, smoking, and a prolonged lupus-sensitive aPTT ratio which could discriminate our patients into subgroups with a very high and very low risk of thrombosis
Summary
Patients with the lupus anticoagulant (LA) are at an increased risk of thrombotic events, which in turn increase the risk of death. While anticoagulation may reduce the risk of thrombosis, it is currently unclear which patient groups are at the highest risk for the development of thrombotic complications [3]. The large uncertainty around the potential determinants of thrombotic risk in LA-positive patients is further aggravated by inconsistent study results on the role of aPL-associated autoantibodies for thrombotic risk stratification, and the rarity of adequately powered prospective studies [1, 7,8,9,10,11,12,13,14,15,16]. A robust risk stratification tool for long-term thrombotic outcomes in patients with LA represents an unmet clinical need [3]
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