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Updated: Jun 10, 2025
Ferric Chloride-induced Murine Thrombosis Models
Published on: September 5, 2016
The third-generation anticoagulants: factors XI, XII, and XIII inhibitors
Sudesh Prajapathi1, Akshyaya Pradhan2, Aditi Mohta3
1Department of Cardiology, King George's Medical University, Shahmina Road, Chowk, Lucknow, Uttar Pradesh, 226003, India.
Insights
Novel anticoagulants targeting factors XIa, XIIa, and XIIIa show promise for preventing thromboembolic events with a potentially lower bleeding risk than current therapies. Further research is needed to establish their long-term efficacy and safety in humans.
Area of Science:
- Pharmacology
- Hematology
- Cardiovascular Medicine
Background:
- Thromboembolic events cause significant global mortality, necessitating effective anticoagulation strategies.
- Current anticoagulants like heparin and vitamin K antagonists, and newer direct oral anticoagulants, carry risks of bleeding.
- Novel drugs targeting coagulation factors XIa, XIIa, and XIIIa are under investigation for improved safety profiles.
Purpose of the Study:
- To review and consolidate findings from clinical trials of novel anticoagulant drugs.
- To evaluate the efficacy and safety of inhibitors targeting coagulation factors XIa, XIIa, and XIIIa.
Main Methods:
- Review of published clinical trial data for FXI, FXII, and FXIII inhibitors.
- Analysis of efficacy in reducing thromboembolic events and safety in terms of bleeding risk.
Main Results:
- Factor XI inhibitors demonstrated superiority over enoxaparin in reducing VTE incidence with a better safety profile in Phase 2 studies.
- Animal studies suggest Factor XII inhibitors may lower bleeding risk.
- Laboratory research indicates Factor XIII inhibition offers potent antithrombotic effects with limited bleeding risks.
Conclusions:
- FXI inhibitors require larger, powered studies to confirm their role in preventing arterial and venous thromboembolic events in high-risk patients.
- Early findings for FXII and FXIII inhibitors are promising but require further human studies to establish therapeutic efficacy and safety.
Background:
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.
Main Body:
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.
Conclusion:
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.
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