Use of direct oral anticoagulants in antiphospholipid syndrome

Abstract

The direct oral anticoagulants (DOACs) are therapeutic alternatives to warfarin and other vitamin K antagonists (VKAs), and constitute the standard of care for many indications. VKAs constitute the conventional therapy for the treatment and secondary thromboprophylaxis of thrombotic antiphospholipid syndrome (APS), but are often problematic, owing to the variable sensitivity of thromboplastins to lupus anticoagulant. Thus, the International Normalized Ratio may not accurately reflect anticoagulation intensity, or be clinically effective. Definition of the current role of DOACs in the treatment of APS is based on limited clinical trial data and information from other sources, including manufacturers' data, case series or cohort studies, and expert consensus. The Rivaroxaban in Antiphospholipid Syndrome (RAPS) randomized controlled trial (RCT), which had a laboratory surrogate primary outcome measure, suggests that rivaroxaban has the potential to be an effective and convenient alternative to warfarin in thrombotic APS patients with a single venous thromboembolism event requiring standard-intensity anticoagulation. However, further studies, in particular to provide better long-term efficacy and safety data, are needed before it can be widely recommended. APS patients are clinically heterogeneous, with the risk of recurrent thrombosis and the intensity of anticoagulation being influenced by their clinical phenotype and risk profile. DOAC trials involving homogeneous thrombotic APS populations, with the antiphospholipid antibody status well defined, will help to optimize the appropriate treatment in APS patient subgroups. Ongoing and emerging DOAC RCTs should provide further information to guide the use of DOACs in APS patients. Optimal identification of APS patients is a key step in working towards improved therapeutic strategies in these individuals.

Seronegative antiphospholipid syndrome: refining the value of “non-criteria” antibodies for diagnosis and clinical management

“…6,76 More recently, non-vitamin K antagonist oral anticoagulants (NOAC) have been investigated in patients with APS with divergent results. 77 Following the results from the Trial on Rivaroxaban in AntiPhospholipid Syndrome (TRAPS), 78 which included triple positive thrombotic APS, rivaroxaban is contraindicated in APS patients with triple aPL positivity. 72 An analysis from the RE-COVER/RE-COVER II and RE-MEDY trials showed similar safety and efficacy of dabigatran in patients with thrombophilia and previous venous thromboembolic events, in whom APS represented the second most common inherited disorders, accounting for 20% of all patients.…”

Influence of DOAC Stop on coagulation assays in samples from patients on rivaroxaban or apixaban

“…Some patients are investigated for haemostatic defects while on these drugs, but the interference in the assays can cause problems with interpretation and there is a significant risk that results can be misinterpreted . Of particular concern would be the potential for a misdiagnosis of acquired haemophilia A in patients with an apparent reduction in factor VIII activity and an apparent factor VIII inhibitor, or the potential for a misdiagnosis of antiphospholipid syndrome in patients with a falsely elevated lupus anticoagulant assay; this may effect patient treatment choices …”

“…an apparent reduction in factor VIII activity and an apparent factor VIII inhibitor, 3 or the potential for a misdiagnosis of antiphospholipid syndrome in patients with a falsely elevated lupus anticoagulant assay; 3,[5][6][7] this may effect patient treatment choices. 8 The recommended method for measuring direct anti-Xa anticoagulants is by LC-MS/MS or a suitably calibrated anti-Xa activity assay; 3 although this will identify patients whose results may be affected by these DOACs, it does not aid interpretation of the results of those assays.…”

What is the appropriate anticoagulation strategy for thrombotic antiphospholipid syndrome?

“…The British Society for Haematology (BSH) guidelines recommend that, due to lack of strong evidence, anticoagulation with warfarin should be considered in patients <50 years with stroke and APS using a target INR of 2·5 (2·0–3·0), but that there is no strong evidence to recommend it over antiplatelet therapy. Standard practice is to maintain a target INR of 2·5, with escalation to a higher target INR should thrombosis recur (Keeling et al , ), although some suggest beginning with a higher target INR (Cohen et al , ).…”