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Reversal Strategies for Intracranial Hemorrhage Related to Direct Oral Anticoagulant Medications.

ABSTRACT: Direct oral anticoagulants (DOACs) are a new class of anticoagulants that directly inhibit either thrombin or factor Xa in the coagulation cascade. They are being increasingly used instead of warfarin or other vitamin K antagonists (VKAs). Adverse side effects of DOACs may result in hemorrhagic complications, including life-threatening intracranial hemorrhage (ICH), though to a much lesser degree than VKAs. Currently there are relatively limited indications for DOACS but their usage is certain to expand with the availability of their respective specific reversal agents. Currently, only idarucizumab (antidote for dabigatran) has been United States Food and Drug Administration- (FDA-) approved, but others (andexanet-? and ciraparantag) may be approved in near future, and the development and availability of such reversal agents have the potential to dramatically change the current anticoagulant use by providing reversal of multiple oral anticoagulants. Until all the DOACs have FDA-approved reversal agents, the treatment of the dreaded side effects of bleeding is challenging. This article is an attempt to provide an overview of the management of hemorrhage, especially ICH, related to DOAC use.

SUBMITTER: Dabi A

PROVIDER: S-EPMC6057345 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Reversal Strategies for Intracranial Hemorrhage Related to Direct Oral Anticoagulant Medications.

Dabi Alok A Koutrouvelis Aristides P AP

Critical care research and practice 20180704

Direct oral anticoagulants (DOACs) are a new class of anticoagulants that directly inhibit either thrombin or factor Xa in the coagulation cascade. They are being increasingly used instead of warfarin or other vitamin K antagonists (VKAs). Adverse side effects of DOACs may result in hemorrhagic complications, including life-threatening intracranial hemorrhage (ICH), though to a much lesser degree than VKAs. Currently there are relatively limited indications for DOACS but their usage is certain t ...[more]

PMID: 30073093

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Project description:Four nonvitamin K antagonist oral anticoagulants (NOACs) are approved for the prevention of stroke in patients with nonvalvular atrial fibrillation and for the treatment of venous thromboembolism. These include the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban. Bleeding is a complication for all anticoagulants and concerns regarding bleeding risk and the suitability of effective reversal strategies may be a barrier to their prescription. Despite the reduced risk of bleeding compared with vitamin K antagonists, questions persist regarding the management of bleeding related to NOAC use.To date, although a number of assays are responsive to NOACs, no single routine laboratory test has been identified to accurately measure the clinical anticoagulation state of patients on NOACs or established as a reliable predictor of bleeding risk. In addition, the establishment of a reliable human bleeding model to test novel inhibitors of the coagulation cascade has proved challenging. Although routine monitoring of anticoagulant levels is not necessary in patients taking NOACs, anticoagulant reversal and a means of measuring reversal may be required for patients who present with bleeding or require urgent surgery. Prothrombin complex concentrates are pooled plasma products containing varying amounts of inactive vitamin K-dependent clotting factors in addition to vitamin K-dependent proteins and can replenish factors in the intrinsic and extrinsic coagulation cascade, reversing an anticoagulant effect. Only one agent, idarucizumab, has been approved for rapid reversal of dabigatran-induced anticoagulation and one more agent, andexanet alfa, has been submitted for approval to reverse the anticoagulatory effects of direct and indirect factor Xa inhibitors.This review discusses the laboratory tests available for assessing anticoagulation, human models of bleeding, and the use of current strategies-including prothrombin complex concentrates for reversal of anticoagulation by NOACs-to manage bleeding in patients.

Dataset Information

Reversal Strategies for Intracranial Hemorrhage Related to Direct Oral Anticoagulant Medications.

Publications

Reversal Strategies for Intracranial Hemorrhage Related to Direct Oral Anticoagulant Medications.

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