Abstract
Background:Chronic anticoagulation with vitamin K antagonists (VKA) is the standard treatment to prevent thrombotic events in antiphospholipid syndrome (APS). But in recent years treatment schemes began to include rivaroxaban. Use of direct oral anticoagulants (DOAC) is an attractive and often preferred alternative to VKAs in other medical settings owing to greater ease of use, fewer food and drug interactions, and lower bleeding risks [1].However, according to last guidelines, rivaroxaban should not be used in patients with triple aPL positivity due to the high risk of recurrent events [2].Objectives:1.To determine the risk of recurrent thrombosis in single or double positive APS patients treated with rivaroxaban.2.Find out possible association between presence of particular antiphospholipid antibodies or high level of lupus anticoagulant (LA) and type of vascular events.Methods:33 patients with confirmed APS (25 female (75.8%), 8 male (24.2%), mean age 43.2±11.6 years) were included in the study. 17 (51.5%) of investigated patients had primary APS, in remaining 16 (48.5%) APS was included in the framework of SLE. 18 (54.5%) patients were treated with warfarin 2.5-7.5 mg/daily, 15 (45.5%) patients - with rivaroxaban 20mg/daily for a follow-up period of 12 months. The data is introduced as odds ratios (OR) with 95% confidence interval (CI). The results were considered significant when p <0.05.Results:At baseline 21 (63.6%) patients had history of arterial thrombosis, 10 (30.3%) - venous thrombosis, 17 (51.5%) - pregnancy loss. According to results of serum immunology check, 29 (87.9%) patients were anticardiolipin antibody (ACA) positive, 9 (27.3%) - LA positive, 19 (57.6%) - anti-ß2-glycoprotein antibodies (anti-ß2-gp) positive; 20 (60.6%) patients were double positive (12 (36.4%) of them had positive ACA and anti-ß2-gp, 6 (18.2%) - ACA and LA, and 2 (6.1%) - anti-ß2-gp and LA), 4 (12.1%) patients were triple positive.No association between vascular event and/or pregnancy loss in patients with single positive ACA was found. We have found positive association between arterial thrombosis and single positive anti-ß2-gp (OR /CI 95%/ = 5.0 /2.08 – 23.06/, p< 0.05), positive association between positive LA and venous thrombosis (OR /CI 95%/ = 10 /1.7-57.7/, p< 0.05), strong positive association between positive LA and thromboembolism of pulmonary artery (OR /CI 95%/ = 46.0 /4.0-525.1/, p< 0.001), negative association between positive LA and pregnancy loss (OR /CI 95%/ =0.06 /0.03 – 0.1/, p< 0.01).Risk of thrombosis and/or pregnancy loss was not significantly increased in double positive patients, but triple positive patients had increased risk of venous thrombosis (OR /CI 95%/ =9.4 /3.2 – 105.8/, p<0.04).Recurrent thrombosis was detected in 16 patients: 2 patients (12.5%) were on warfarin, 14 (87.5%) - on rivaroxaban (10 (71.4%) arterial thrombosis, 4 (28.6%) venous thrombosis).No association between warfarin 2.5-7.5 mg/daily and occurrence of recurrent thrombosis was detected. An association between use of warfarin and increased risk of bleeding was found, but the risk was not significant (OR /CI 95%/ = 7.0 /0.7 – 66/, p= 0.09). Rivaroxaban 20 mg/daily was associated with recurrent thrombosis not only for triple positive patients (p< 0.02), but also in double positive patients (OR /CI 95%/ = 21.3 /1.8 – 251/, p< 0.04).Conclusion:Rivaroxaban does not prevent recurrent thrombosis not only in triple positive patients, but also in single and double positive APS patients. Type of antiphospholipid antibodies can be predictive for the type of further vascular event.
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