Management of Elective Surgery and Emergent Bleeding with Direct Oral Anticoagulants.

PURPOSE OF REVIEW: The purpose of this review was to offer practical management strategies for when patients receiving direct oral anticoagulants require elective surgery or present with bleeding complications. RECENT FINDINGS: Clinical practice guidelines are now available on the timing of periprocedural interruption of treatment with the newer direct oral anticoagulants based on their pharmacodynamics and pharmacokinetics and based on findings from cohort studies and clinical trials. An antibody that reverses the effects of dabigatran is now available, and a factor Xa decoy is being developed as an antidote to apixaban, betrixaban, edoxaban, and rivaroxaban. The timing of interruption of direct oral anticoagulants for elective surgery is based on multiple factors, including pharmacologic properties and interactions, the patient's renal function, and the type of planned surgery. There is little role for low-molecular-weight heparin bridging. Idarucizumab is the treatment of choice for dabigatran-related life-threatening bleeding, while andexanet alfa is being developed to reverse factor Xa inhibitors.

Current Trends in Anticoagulation Bridging for Patients With Chronic Atrial Fibrillation on Warfarin Undergoing Endoscopy.

For warfarin-treated patients with atrial fibrillation (AF) at low thromboembolic risk, recent studies have shown harm associated with periprocedural bridging using low-molecular-weight heparin. Clinician surveys have indicated a preference toward excessive bridging, especially among noncardiologists; however, little is known about actual practice patterns in these patients. We performed a retrospective evaluation of bridging in the setting of gastrointestinal endoscopy. We identified 938 patients with AF on warfarin who underwent esophagogastroduodenoscopy or colonoscopy between 2012 and 2016 at a tertiary health center. Urgent, inpatient, or advanced endoscopic procedures were excluded. Clinical variables were abstracted using a predefined data dictionary. Values were expressed as means and compared using a t test or a chi-squared test as appropriate. Three hundred seventy-four patients met criteria for analysis. Twenty-five percent of these patients received bridging therapy, including 11% of patients with CHADS2 scores of 0 to 2 without valvular AF or previous venous thromboembolism. Of the clinical variables assessed, CHADS2, CHA2DS2-VASc, and a history of stroke were the strongest predictors of bridging. Cardiologists were also significantly less likely to prescribe bridging than noncardiology providers (18% vs 30%, p = 0.011); this effect was significant when controlling for CHADS2, CHA2DS2-VASc, or stroke history. In conclusion, patients with AF on warfarin receive excessive low-molecular-weight heparin bridging in the setting of endoscopy; the lower rates of bridging observed among cardiologists suggests a need for their increased involvement in this decision making.

Reversing factor Xa inhibitors - clinical utility of andexanet alfa.

Approximately half of patients started on an oral anticoagulant in the USA now receive one of the newer direct oral anticoagulants (DOACs). Although there is an approved reversal agent for the direct thrombin inhibitor dabigatran, a specific reversal agent for the anti-factor Xa (FXa) DOACs has yet to be licensed. Unlike the strategy to reverse the only oral direct thrombin inhibitor with idarucizumab, which is a humanized monoclonal antibody fragment, a different approach is necessary to design a single agent that can reverse multiple anti-FXa medications. Andexanet alfa is a FXa decoy designed to reverse all anticoagulants that act through this part of the coagulation cascade including anti-FXa DOACs, such as apixaban, edoxaban and rivaroxaban, and indirect FXa inhibitors such as low-molecular-weight heparins. This narrative reviews the development of andexanet alfa and explores its basic science, pharmacokinetics/pharmacodynamics, animal models, and human studies.