New Insights into Nonvitamin K Antagonist Oral Anticoagulants' Reversal of Intracerebral Hemorrhage

Abstract

The nonvitamin K antagonist oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban are associated with an equal or lower incidence of stroke and systemic embolism and a much lower incidence of intracranial hemorrhage and hemorrhagic stroke than warfarin is, without the need for routine laboratory monitoring. However, reversal strategies are not currently established in the case of NOAC-related hemorrhagic stroke. In emergency situations, well-defined management for NOAC-related hemorrhagic stroke may improve clinical outcomes. Thus, in this chapter, general measures initially required to prevent the expansion of intracerebral hematomas, charcoal administration to reduce NOAC absorption from the gastrointestinal tract, application of hemodialysis to remove dabigatran, and coagulation factor therapy including 4-factor prothrombin complex concentrate and recombinant activated factor VII are reviewed. The specific reversal agents idarucizumab, which is a monoclonal antibody against dabigatran; andexanet alfa, a recombinant human factor Xa decoy for Xa inhibitors; and PER977, a small synthetic molecule for reversal of both Xa and thrombin inhibitors, are currently under development. These agents will facilitate the clinical management of NOAC-associated hemorrhagic stroke and other severe bleeding.

Surgically Treated Intracerebral Haemorrhage : Pathophysiology and Clinical Aspects

“…Coagulopathy and a sustained high systolic blood pressure (SBP) create an increased risk of ongoing bleeding, and are both associated with neurological deterioration (33). The risk of poor outcome following ICH is increased for all different anticoagulants in current use (28), although NOAC-treated ICH patients have smaller ICH volume, are less prone to haematoma expansion and have lower mortality than Warfarin-treated ICH patients (34)(35)(36)(37)(38)(39)(40). Approximately 25% of ICH patients are on antiplatelet therapy and their prognosis is worse than that of patients not on antiplatelet therapy (41).…”

Critical Care Management of Intracerebral Hemorrhage

“…4,38 Until recently, PCCs (4F or FEIBA) have been the only available reversal agents for NOAC-related hemorrhages 4,39 given a lack of specific antidotes. 40 However, the U.S Food and Drug Administration (FDA) recently approved idarucizumab, an antibody fragment that rapidly and effectively reverses dabigatran. 41,42 Additionally, andexanet alfa, a high-affinity factor Xa decoy, is on the fast track for FDA approval for the reversal of factor Xa inhibitors given its designation as "breakthrough therapy."…”