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Interactions between antiphospholipid antibodies, oral anticoagulants and haemostasis activation in thrombotic antiphospholipid syndrome

Jayakody Arachchillage, DR; (2015) Interactions between antiphospholipid antibodies, oral anticoagulants and haemostasis activation in thrombotic antiphospholipid syndrome. Doctoral thesis , UCL (University College London). Green open access

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Abstract

Antiphospholipid antibodies (aPL) are associated with an increased thromboembolic risk but the mechanism is unclear. Warfarin anticoagulation has traditionally been employed in thrombotic antiphospholipid syndrome (APS), but direct oral anticoagulants such as rivaroxaban have recently become available. The aims of this thesis were to: 1. Investigate the frequency, mechanism and clinical associations of activated protein C resistance (APCr) in thrombotic APS 2. Assess the effects of rivaroxaban on lupus anticoagulant tests 3. Investigate the efficacy of rivaroxaban in terms of thrombin generation (TG) and haemostasis activation markers in thrombotic patients with or without APS Thrombotic APS patients had greater APCr than disease controls. Nearly 50% of APS patients had anti-protein C (anti-PC) antibodies; those with high avidity antibodies had significantly greater APCr using either exogenous activated PC or activation of endogenous PC with Protac®. High avidity anti-PC antibodies were strongly associated with a severe thrombotic phenotype in APS. There was a wide variation in the sensitivity of thromboplastin reagents to rivaroxaban. Of the six commonly used thromboplastin reagents studied, Neoplastin®R was the most sensitive while Innovin® and Thromborel®S were the least sensitive. False positive dilute Russell’s viper venom time occurred in patients with therapeutic levels of rivaroxaban. Taipan /Ecarin venom clotting time ratio and Textarin time were not affected irrespective of the rivaroxaban level, enabling accurate detection of LA. In vitro studies showed that aPL did not influence the anticoagulant activity of rivaroxaban as measured by TG and anti-Xa assays. Both rivaroxaban and warfarin achieved effective anticoagulation, as assessed by inhibition of TG and in-vivo coagulation activation markers in patients with and without APS.

Type: Thesis (Doctoral)
Title: Interactions between antiphospholipid antibodies, oral anticoagulants and haemostasis activation in thrombotic antiphospholipid syndrome
Event: University College London
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
URI: https://discovery.ucl.ac.uk/id/eprint/1470418
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