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Emerging anticoagulant strategies

James C. Fredenburgh, Peter L. Gross and Jeffrey I. Weitz

Abstract

Despite the introduction of direct oral anticoagulants (DOACs), the search for more effective and safer antithrombotic strategies continues. Better understanding of the pathogenesis of thrombosis has fostered two new approaches to achieving this goal. First, evidence that thrombin may be as important as platelets to thrombosis at sites of arterial injury and that platelets contribute to venous thrombosis has prompted trials comparing anticoagulants with aspirin for secondary prevention in arterial thrombosis and aspirin with anticoagulants for primary and secondary prevention of venous thrombosis. These studies will help to identify novel treatment strategies. Second, emerging data that naturally occurring polyphosphates activate the contact system and that this system is critical for thrombus stabilization and growth have identified factors (F) XII and FXI as targets for new anticoagulants that may be even safer than the DOACs. Studies are needed to determine whether FXI or FXII is the better target and to compare the efficacy and safety of these new strategies with current standards of care for prevention or treatment of thrombosis. Focusing on these advances, this paper outlines how treatment strategies for thrombosis are evolving and describes the rationale and approaches to targeting FXII and FXI. These emerging antithrombotic strategies should address unmet needs and reduce the systemic under use of anticoagulation because of the fear of bleeding.

  • Submitted September 14, 2016.
  • Accepted October 22, 2016.