Direct oral anticoagulants (DOAC) – Management of emergency situations

Abstract

The worldwide increase in the aging population and the associated increase in the prevalence of atrial fibrillation and venous thromboembolism as well as the widespread use of direct oral anticoagulants (DOAC) have resulted in an increase of the need for the management of bleeding complications and emergency operations in frail, elderly patients, in clinical practice. When severe bleeding occurs, general assessment should include evaluation of the bleeding site, onset and severity of bleeding, renal function, and concurrent medications with focus on antiplatelet drugs and nonsteroidal anti-inflammatory drugs (NSAID). The last intake of the DOAC and its residual concentration are also relevant. The site of bleeding should be immediately localized, anticoagulation should be interrupted, and local measures to stop bleeding should be taken. In life-threatening bleeding or emergency operations immediate reversal of the antithrombotic effect may be indicated. If relevant residual DOAC-concentrations are expected and surgery cannot be postponed, prothrombin complex concentrate (PCC) and/or a specific antidote should be given. While idarucizumab, the specific antidote for dabigatran, has been recently approved for clinical use, the recombinant factor X protein andexanet alfa, an antidote for the reversal of inhibitors of coagulation factor Xa, and ciraparantag, a universal antidote, are not available. Future cohort studies are necessary to assess the efficacy and safety of specific and unspecific reversal agents in "real-life" conditions. This was the rationale for introducing the RADOA-registry (RADOA: Reversal Agent use in patients treated with Direct Oral Anticoagulants or vitamin K antagonists), a prospective non-interventional registry, which will evaluate the effects of specific and unspecific reversal agents in patients with life-threatening bleeding or emergency operations either treated with DOACs or vitamin K antagonists.

The impact of prothrombin complex concentrates when treating DOAC-associated bleeding: a review

“…A further prospective, non-interventional study (the Reversal Agent use in patients treated with Direct Oral Anticoagulants or vitamin K antagonists [RADOA] registry) is currently being conducted in Germany to evaluate the reversal strategies used in patients treated with oral anticoagulants [70].…”

Severe Hemorrhage Associated With Oral Anticoagulants

“…The RADOA registry is a prospective, observational, non-interventional, open-label, investigator-initiated multicenter German registry, documenting the management of severe hemorrhages and/or urgent interventions in patients treated with VKA or DOAC. The aims and design of this registry have already been described elsewhere (18).…”

Novel Anticoagulant Treatment for Pulmonary Embolism with Direct Oral Anticoagulants Phase 3 Trials and Clinical Practice

“…An ongoing prospective noninterventional registry including patients with life-threatening bleeding or emergency operations either treated with DOACs or VKAs will aim to evaluate effects of specific and unspecific reversal agents. 45 Idarucizumab is a humanized monoclonal antibody fragment derived from an IgG1 isotype molecule, whose target is the direct thrombin inhibitor dabigatran. Andexanet alfa is a recombinant modified human factor Xa decoy protein that has been shown to reverse the inhibition of factor Xa (rivaroxaban, apixaban, edoxaban, and heparin).…”