Therapeutic strategies for thrombosis: new targets and approaches

Existing antiplatelet and anticoagulant agents for the prevention and treatment of thrombosis are associated with bleeding risk. Here, Mackman and colleagues provide an overview of haemostasis and thrombosis and assess the advantages and limitations of existing antithrombotics. The emerging antithrombotic targets and agents in development as well as the associated challenges are discussed. Antiplatelet agents and anticoagulants are a mainstay for the prevention and treatment of thrombosis. However, despite advances in antithrombotic therapy, a fundamental challenge is the side effect of bleeding. Improved understanding of the mechanisms of haemostasis and thrombosis has revealed new targets for attenuating thrombosis with the potential for less bleeding, including glycoprotein VI on platelets and factor XIa of the coagulation system. The efficacy and safety of new agents are currently being evaluated in phase III trials. This Review provides an overview of haemostasis and thrombosis, details the current landscape of antithrombotic agents, addresses challenges with preventing thromboembolic events in patients at high risk and describes the emerging therapeutic strategies that may break the inexorable link between antithrombotic therapy and bleeding risk.