Strategies for the prevention and treatment of bleeding in patients treated with dabigatran: an update

ABSTRACT

Introduction

Although dabigatran is safer than vitamin K antagonists, bleeding still occurs. Bleeding is an important cause of short-term morbidity and rarely mortality and can also have long-term consequences that are often under-appreciated. After bleeding, patients often do not restart treatment or are poorly adherent, which is associated with increased thromboembolism and mortality. Consequently, we need strategies to prevent and treat bleeding in patients with atrial fibrillation treated with dabigatran.

Areas covered

We review a) relevant dabigatran pharmacology, b) the burden and consequences of bleeding, c) how to identify patients at high risk of bleeding; and d) existing and novel approaches to prevent and treat bleeding in dabigatran-treated patients.

Expert opinion

Concerns about the risk of bleeding associated with anticoagulant therapy and emerging evidence of increased risk of thromboembolism and mortality after bleeding highlight the need for improved approaches to prevention and treatment of bleeding. Future research priorities should focus on improving our ability to prevent bleeding by identifying modifiable risk factors and the development of safer agents. The current front runners include drugs that selectively target the contact pathway of coagulation (e.g. factor XI). Targeting upstream drivers of thrombosis (e.g. inflammation) could help to further reduce the risk of thromboembolism.

KEYWORDS:

• Dabigatran
• idarucizumab
• prothrombin complex concentrate
• bleeding
• activated partial thromboplastin time
• ecarin clotting time
• thrombin time

Article highlights

• Although long-term anticoagulation with dabigatran is safer than with vitamin K antagonists, bleeding can still occur. Bleeding is an important cause of short-term morbidity and mortality and has long-term consequences that are often under-appreciated. Identifying and addressing modifiable risk factors for bleeding when initiating dabigatran could minimize bleeding risk.

• The approach to management of bleeding in patients receiving dabigatran include determining the site and cause of bleeding, assessing the severity of bleeding, and evaluating whether residual drug is contributing to ongoing bleeding.

• Time from last administration, renal function, and coagulation assays such as qualitative assays (e.g. activated partial thromboplastin time and thrombin clotting time) or quantitative assays (e.g. dilute thrombin time, ecarin clotting time, and ecarin chromogenic assays) if available, could help gauge whether residual drug might be contributing to ongoing bleeding.

• Approaches to treat major bleeding in patients treated with dabigatran include reversal of its anticoagulant effect with idarucizumab, or if not available, the use of pro-hemostatic agents (e.g. prothrombin complex concentrate, activated prothrombin complex concentrate, recombinant activated factor VII).

• In selected patients, ancillary approaches to reduce dabigatran absorption, such as activated charcoal, or to enhance clearance, such as hemodialysis or hemofiltration may be considered.

• Patients with a history of bleeding complications often do not restart treatment or are poorly adherent if they restart, both of which are associated with an increased risk of thromboembolism and mortality.

Disclosure statement

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

K Xu was sponsored by Shanghai Sailing Program [20YF1444200].