title: Rivaroxaban limits complement activation compared with warfarin in antiphospholipid syndrome patients with venous thromboembolism.
abstract: Essentials Complement activation has a pathogenic role in thrombotic antiphospholipid syndrome (APS). Coagulation proteases such as factor Xa can activate complement proteins. Complement activation markers were elevated in anticoagulated thrombotic APS patients. Complement activation decreased in APS patients switching from warfarin to rivaroxaban.
  
  
  
  Background Complement activation may play a major role in the pathogenesis of thrombotic antiphospholipid syndrome (APS). Coagulation proteases such as factor Xa can activate complement proteins. Aims To establish whether rivaroxaban, a direct factor Xa inhibitor, limits complement activation compared with warfarin in APS patients with previous venous thromboembolism (VTE). Methods A total of 111 APS patients with previous VTE, on warfarin target INR 2.5, had blood samples taken at baseline and at day 42 after randomization in the RAPS (Rivaroxaban in Antiphospholipid Syndrome) trial. Fifty-six patients remained on warfarin and 55 switched to rivaroxaban. Fifty-five normal controls (NC) were also studied. Markers of complement activation (C3a, C5a, terminal complement complex [SC5b-9] and Bb fragment) were assessed. Results APS patients had significantly higher complement activation markers compared with NC at both time-points irrespective of the anticoagulant. There were no differences between the two patient groups at baseline, or patients remaining on warfarin at day 42. In 55 patients randomized to rivaroxaban, C3a, C5a and SC5b-9 were lower at day 42 (median (ng mL-1) [confidence interval] 64 [29-125] vs. 83 [35-147], 9 [2-15] vs. 12 [4-18] and 171 [56-245] vs. 201 [66-350], respectively) but levels of Bb fragment were unchanged. There were no correlations between rivaroxaban levels and complement activation markers. Conclusions APS patients with previous VTE on warfarin exhibit increased complement activation, which is likely to occur via the classical pathway and is decreased by rivaroxaban administration. Rivaroxaban may therefore potentially provide an additional benefit to its anticoagulant effect in this patient group by limiting complement activation.
authors.affiliation: Department of Haematology, Haemostasis Research Unit, University College London, London, UK.
authors.forename: D R J
authors.initials: DR
authors.lastname: Arachchillage
authors.affiliation: Department of Haematology, Haemostasis Research Unit, University College London, London, UK.
authors.forename: I J
authors.initials: IJ
authors.lastname: Mackie
authors.affiliation: Department of Haematology, Haemostasis Research Unit, University College London, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Efthymiou
authors.affiliation: Department of Haematology, Haemostasis Research Unit, University College London, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Chitolie
authors.affiliation: Thrombosis and Haemophilia, Guy's and St Thomas' NHS Foundation Trust, London, UK.|Department of Haematology, Kings College London, London, UK.
authors.forename: B J
authors.initials: BJ
authors.lastname: Hunt
authors.affiliation: Centre for Rheumatology, Division of Medicine, University College London, London, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Isenberg
authors.affiliation: Lupus Research Unit, Guy's and St Thomas' NHS Foundation Trust, London, UK.|Department of Rheumatology, Kings College London, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Khamashta
authors.affiliation: Department of Haematology, Haemostasis Research Unit, University College London, London, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Machin
authors.affiliation: Department of Haematology, Haemostasis Research Unit, University College London, London, UK.|Department of Haematology, University College London Hospitals NHS Foundation Trust, London, UK.
authors.forename: H
authors.initials: H
authors.lastname: Cohen
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000627:therapeutic use*; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D001777:Blood Coagulation / Q000187:drug effects*; D003167:Complement Activation; D015951:Factor Xa / Q000737:chemistry; D065427:Factor Xa Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D000069552:Rivaroxaban / Q000627:therapeutic use*; D013927:Thrombosis / Q000097:blood; D054556:Venous Thromboembolism / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D014859:Warfarin; D000069552:Rivaroxaban; D015951:Factor Xa
keywords: anaphylatoxins; antiphospholipid syndrome; complement; rivaroxaban; venous thromboembolism; warfarin