20 In the same study, infusion of 4-factor PCC (50 U/kg) did not correct the APTT, ECT, or TT in dabigatran-treated subjects (150 mg twice daily for 2.5 days). In a randomized crossover study, infusion of 4-factor PCC (50 U/kg) corrected PT prolongation and abnormal endogenous thrombin potential (ETP) compared with placebo in healthy subjects receiving rivaroxaban (20 mg twice daily for 2.5 days). PCC is a plasma-derived product containing vitamin K -dependent coagulation factors II, IX and X (3-factor PCC) or II, VII, IX and X (4-factor PCC) developed for reversal of vitamin K antagonist anticoagulant (VKA) effect. Specific reversal agents, such as idarucizumab (a monoclonal antibody fragment that binds dabigatran) and andexanet alfa (a recombinant factor Xa variant that binds factor Xa inhibitors but lacks coagulant activity), are in clinical development. Nonspecific reversal agents (eg, prothrombin complex concentrate, activated prothrombin complex concentrate) are of unproven benefit, carry a risk of thrombosis, and should be reserved for severe bleeding. Patients with minor and moderate DOAC-associated bleeding can be treated with supportive care and general hemostatic measures. A normal prothrombin time probably excludes excess levels of rivaroxaban and edoxaban, but not apixaban.

Factor Xa inhibitors may be quantified with an anti-Xa assay calibrated with drug-specific standards. A normal thrombin time excludes clinically relevant levels and a normal activated partial thromboplastin time probably excludes excess levels of dabigatran. The dilute thrombin time and ecarin-based assays are able to quantify dabigatran across a broad range of concentrations, but are not widely available. Although the direct oral anticoagulants (DOACs) do not require routine monitoring and reduce bleeding compared with warfarin, there are special circumstances in which laboratory measurement or reversal of their anticoagulant effect may be indicated.

Mitherades v universal antidote