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Purpose: The purpose of this article is to describe the role of andexanet alfa as a reversal agent in the management of bleeding complications associated with direct oral anticoagulants (DOACs). Summary: Over the past several years, DOACs are increasingly being used in the management of patients with non-valvular atrial fibrillation or stroke prevention. Management of major bleeding in DOAC therapy includes supportive therapy and addressing any factors that are contributing to blood loss. Additionally, there may a need to expedite the removal of any anticoagulation effects by removing or neutralizing the anticoagulant. Until recently, there was no specific reversal agent for DOACs; management approaches were limited to util ©Wizing concentrated clotestern University oft Health Sciencesing factors or fresh frozen plasma. The FDA granted expedited approval of andexanet alfa as a specific reversal agent for the DOACs to meet this unmet need. Conclusion: In clinical trials, andexanet alfa demonstrated a significant reduction in anti-Xa activity in patients with a major bleeding event on apixaban or rivaroxaban. The clinical benefit of this anti-Xa activity reduction has yet to be demonstrated in a randomized controlled trial. The current lack of randomized controlled trials demonstrating clinical benefit and the high cost of the drug has limited the widespread use of this antidote.

Background & Aims Hospitalized patients with acute severe ulcerative colitis (ASUC) often require surgery. Although the tumor necrosis factor antagonist infliximab is an effective salvage therapy to prevent colectomy in patients with ASUC, optimal dosing is unclear. Calculated infliximab clearance has been associated with important outcomes in patients with ulcerative colitis, but its utility in patients with ASUC has not been established. We assessed the relationship between calculated the baseline infliximab clearance before infliximab salvage therapy and the requirement for colectomy in patients hospitalized for ASUC. Methods We obtained data from hospitalized patients with ASUC who initiated infliximab therapy. We then calculated the baseline infliximab drug clearance in these patients based on an existing formula. The primary aim was to compare clearance between patients who required colectomy 6 months later and patients who did not require colectomy. Receiver operating characteristic curve analyses evaluated clearance thresholds for colectomy. Multivariable logistic regression analysis evaluated factors associated with colectomy. Results In 39 patients with ASUC, the median baseline calculated clearance was higher in patients requiring colectomy at 6 months than in patients without colectomy (0.733 vs 0.569 L/d; P = .005). An infliximab clearance threshold of 0.627 L/d identified patients who required colectomy with 80.0% sensitivity and 82.8% specificity (area under the curve, 0.80). A higher proportion of patients with infliximab clearance of 0.627 L/d or more underwent colectomy within 6 months (61.5%) than patients with lower infliximab clearance values (7.7%) (P = .001). Multivariable analysis identified baseline infliximab clearance as the only factor associated with colectomy. The infliximab dose in the hospital was higher in patients who required colectomy. Results were similar at 30 days and 1 year. Conclusions In patients hospitalized with ASUC, higher values of calculated infliximab clearance before infliximab administration is associated with higher rates of colectomy. Although patients who required colectomies received higher doses, data on infliximab concentrations are lacking. Infliximab pharmacokinetic models are needed for patients with ASUC to allow comparative trials on clearance-based vs standard dosing.