Monitoring and reversal strategies for new oral anticoagulants

Abstract

Thrombin inhibitor dabigatran and factor Xa inhibitors rivaroxaban, apixaban and edoxaban form a new class of non-vitamin K antagonist oral anticoagulants and have been extensively studied in patients with venous thromboembolism and atrial fibrillation. They offer anticoagulation that is as effective and at least as safe compared to warfarin without the need for routine laboratory monitoring; however, no reversal strategies are currently validated in case of a non-vitamin K antagonist oral anticoagulant-associated bleed. In emergency situations, laboratory drug measurement and well-defined management for non-vitamin K antagonist oral anticoagulant-induced hemorrhage may improve clinical outcome. In this review, the merits and limitations of the routine coagulation tests and some of the more specific laboratory assays are compared. Furthermore, prohemostatic measures are reviewed and the recommended strategies in case of bleeding are summarized. Specific reversal agents are currently under development (idarucizumab for dabigatran, andexanet alfa for Xa inhibitors, and PER977 for both Xa- and thrombin inhibitors), which will facilitate clinical management of severe bleeding and emergency surgery.

Keywords:

• andexanet
• antidote
• apixaban
• bleeding
• dabigatran
• idarucizumab
• monitoring
• oral anticoagulants
• reversal strategies
• rivaroxaban

Financial & competing interests disclosure

P Verhamme has served as a consultant and speaker for Boehringer Ingelheim, Bayer Healthcare, Daiichi Sankyo and Pfizer, and has received research support from Boehringer Ingelheim, Bayer Healthcare and Daiichi Sankyo. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Unmonitored administration of non-vitamin K antagonists oral anticoagulants (NOACs) was shown to be as effective and at least as safe, as well-managed warfarin.

• The available NOACs inhibit thrombin (factor IIa) or factor Xa, both pivotal proteins in the coagulation cascade.

• For interpretation of coagulation assays – taking into account the short half-life of available NOACs – it is crucial to know the time of blood sampling with respect to the last intake.

• For monitoring of the pharmacodynamic effect of NOACs, there are general, qualitative (activated partial thromboplastin time for dabigatran and prothrombin time for rivaroxaban) and specific, quantitative (diluted thrombin time for dabigatran, chromogenic anti-Xa assay for factor Xa inhibitors) laboratory assays, that may help clinical decision making in case of emergency surgery or bleeding complications.

• Prothrombin complex concentrates support hemostasis for patients with recent intake of dabigatran and factor Xa inhibitors who suffer from potentially life-threatening bleeding.

• Specific reversal agents are currently being validated.

Notes