New ACC guidance addresses acute bleeding in anticoagulated patients

The American College of Cardiology (ACC) released new guidelines for patients with all levels of acute bleeding receiving either direct oral anticoagulants (DOACs) or warfarin, as detailed in a recent issue of JAMA.

“The ACC Expert Consensus Decision Pathways (ECDPs) focus on concise decision pathways, key points of care, or both,” wrote authors Adam S. Cifu, MD, and Irsk Anderson, MD, University of Chicago, Chicago, IL. “Unlike traditional guidelines, the pathways address clinical decisions for which there is insufficient high-quality evidence and that thus might be influenced by expert opinion.”

Hemorrhage is the main risk associated with oral anticoagulants (OACs), and management of such bleeding has become more challenging with the approval of four different DOACs since 2010. Major bleeding case-fatality rates for DOACs were 7.57%; and for warfarin, 11.05%, according to a meta-analysis that included 13 randomized clinical trials and 102,707 subjects.

“For bleeding that occurs in an essential organ (eg, central nervous system, pericardium, airway) or that is life-threatening, the guideline recommends that the OAC be at least temporarily discontinued, that local therapy and supportive measures be provided, and, when indicated, that a reversal agent be administered,” the experts wrote.

Reversal agents for DOACs include:

• 5-10 mg of intravenous (IV) vitamin K and IV 4-factor prothrombin complex concentrate (4F-PCC) for warfarin
• IV idarucizumab (a monoclonal antibody) or IV 4F-PCC/activated prothrombin complex concentrate (aPCC) for dabigatran
• IV 4F-PCC or intravenous aPCC for apixabin, edoxaban, or rivaroxaban

Notably, the experts recommend 4F-PCC instead of plasma as first-line therapy for warfarin reversal.

Laboratory tests that detect drug levels and concentrations are available for all FDA-approved DOACs. In emergent situations, the experts recommend assessing patients for these levels and concentrations, although it’s not yet clear whether knowing the exact DOAC drug levels is clinically relevant for reversal.

For dabigatran, normal levels of dilute thrombin time (TT), ecarin clotting time (ECT), ecarin chromogenic assay (ECA), or activated partial thromboplastin time (aPTT) likely indicate clinically insignificant drug levels.

For apixaban, edoxaban, and rivaroxaban, negative anti-factor Xa assay activity likely discounts clinically important drug levels. But prolonged prothrombin time suggests a clinically significant drug level.

Many of these specialized assays, though, are not routinely available to clinicians, the authors acknowledged.

“In patients with major bleeding and lack of measurable DOAC, the administration of reversal agents and the complication of thromboembolic events can be avoided,” the ACC experts concluded. “At present, no specific antidotes to the factor Xa inhibitors (apixaban, edoxaban, and rivaroxaban) exist.”