The third-generation anticoagulants: factors XI, XII, and XIII inhibitors

Arterial or venous thromboembolic events are responsible for one-fourth of all deaths worldwide. Anticoagulants are the mainstay for the prevention and treatment of venous thromboembolic events (VTE). Heparin and vitamin K antagonists were the first non-specific medications used in anticoagulant therapy, followed by safer alternatives, such as fondaparinux, argatroban, and direct oral anticoagulants. However, the latter bear the risk of potentially lethal internal bleeding. Novel drugs inhibiting various coagulation factors, such as factors XIa, XIIa, and XIIIa, appear to have a lesser risk of bleeding and are in the spotlight. This review aims to consolidate findings from published clinical trials of newer drugs inhibiting factors XIa, XIIa, and XIIIa.

Factor XI inhibitors have been researched more extensively as compared to factor XII and factor XIII inhibitors. Phase 2 study results of factor XI inhibitors indicated their superiority over enoxaparin for reduction of VTE incidence and better safety profile in terms of bleeding. Factor XII inhibitors also hold the promise of lowering the risk of bleeding, as indicated in animal studies. Further human studies would ensure their safety and applicability in the human population. Numerous laboratory researches have revealed, the potent antithrombotic profile of factor XIII inhibition with limited bleeding risks.

Larger statistically powered studies could supplement data to establish the role of FXI inhibitors in the prevention of both arterial and venous thromboembolic events in high-risk populations. While early results of factor XII and factor XIII inhibitors look promising, they still have a long road ahead before their therapeutic efficacy in humans is established.