A review of guidelines on anticoagulation reversal across different clinical scenarios – Is there a general consensus?

Abstract

Anticoagulation is key to the treatment/prevention of thromboembolic events. The primary complication of anticoagulation is serious or life-threatening hemorrhage, which may necessitate prompt anticoagulation reversal; this could also be required for nonbleeding patients requiring urgent/emergent invasive procedures. The decision to reverse anticoagulation should weigh the benefit-risk ratio of supporting hemostasis versus postreversal thrombosis. We appraise the available guidelines/recommendations for vitamin K antagonist (VKA) and direct oral anticoagulant (DOAC) reversal in the management of major bleeding, and also assess recent clinical data that may not yet be reflected in official guidance. In general, available guidelines are consistent in their recommendations, advocating administration of vitamin K and 4-factor prothrombin complex concentrates (4F-PCCs) rather than fresh frozen plasma to patients with VKA-associated intracranial hemorrhage and lifethreatening bleeding, and specific reversal agents as essential therapy for DOAC reversal in those same severe conditions. However, guidelines also recommend off-label use of PCCs for DOAC reversal when specific reversal agents are unavailable. Limited recent evidence generally support the latter recommendation, but guidelines are likely to evolve as more data become available.

Pharmacologic Agents Used to Reverse the Anticoagulant Effect of Common Anticoagulants

“…This half-life increases as renal function declines. Clinical studies show that idarucizumab acts rapidly to normalize TT and reduce dabigatran concentrations 1,2,27,28 …”

“…Clinical trials have demonstrated that idarucizumab is safe and effective at reversing the anticoagulant effects of dabigatran. The adverse effects attributed to idarucizumab administration include hypokalemia, delirium, constipation, pyrexia, and pneumonia 1,2,27,28 …”

“…This feature prevents andexanet from having any type of anticoagulant activity. These structural changes allow FXa inhibitors (apixaban, rivaroxaban) to preferentially bind to andexanet instead of endogenous FXa without producing anticoagulant effects 1,2,27,34–36 …”

“…However, the FDA, mandates that pharmaceutical manufacturers support specific research for using andexanet alfa to reverse the anticoagulant effect of specific FXa inhibitors such that precise dosing recommendations can be ascertained for each specific anticoagulant. Of note, the dosing recommendations for andexanet alfa use when reversing the anticoagulant effects of rivaroxaban and apixaban are different 1,2,27,34–36 …”

Use of Idarucizumab in Ischemic Stroke: A National Experience in a Middle Income Country and a Concise Review.

“…As a result, particular emphasis has been placed on developing specific agents capable of reversing DOAC's anticoagulant effect. As a result, andexanet alfa, idarucizumab, and ciraparantag have been evaluated for their potential use in reversing the effects of direct anticoagulants (7). Idarucizumab is a humanized monoclonal antibody fragment that has a high affinity and specificity for dabigatran and is capable of rapidly reversing anticoagulant activity (8).…”