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New antithrombotic strategies are being developed, targeting factor XII (FXII) and factor XI (FXI) for safer anticoagulation. These approaches aim to improve thrombosis treatment and reduce bleeding risks compared to current methods.

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Area of Science:

  • Cardiovascular Medicine
  • Hematology
  • Pharmacology

Background:

  • Direct oral anticoagulants (DOACs) have improved thrombosis treatment, but the search for safer and more effective antithrombotic strategies persists.
  • Understanding thrombosis pathogenesis reveals new therapeutic targets, including the roles of thrombin, platelets, and the contact system.
  • Existing anticoagulation therapies are underused due to concerns about bleeding complications.

Purpose of the Study:

  • To outline evolving antithrombotic treatment strategies.
  • To describe the rationale and approaches for targeting factor XII (FXII) and factor XI (FXI) as novel anticoagulant targets.
  • To address unmet needs in thrombosis prevention and treatment, aiming for improved safety profiles.

Main Methods:

  • Review of current evidence on thrombosis pathogenesis, including the roles of platelets, thrombin, and the contact system.
  • Analysis of ongoing clinical trials comparing anticoagulants with aspirin for arterial and venous thrombosis.
  • Evaluation of emerging data on polyphosphates, FXII, and FXI as targets for new anticoagulant development.

Main Results:

  • Evidence suggests thrombin and platelets play critical roles in arterial and venous thrombosis, respectively, prompting comparative trials.
  • Naturally occurring polyphosphates activate the contact system, highlighting FXII and FXI as potential targets for next-generation anticoagulants.
  • New anticoagulant strategies targeting FXII and FXI may offer improved safety over DOACs, potentially reducing bleeding risks.

Conclusions:

  • Novel antithrombotic strategies targeting FXII and FXI are emerging, offering potential for safer and more effective thrombosis management.
  • Further studies are needed to determine the optimal target (FXI vs. FXII) and compare new strategies against current standards of care.
  • These advancements aim to overcome limitations of current anticoagulation, addressing the underuse due to bleeding fears.