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Updated: Dec 31, 2025
Ferric Chloride-induced Murine Thrombosis Models
Published on: September 5, 2016
Factors IX, XI, and XII: potential therapeutic targets for anticoagulant therapy in atherothrombosis
Vikrant Rai1, Marcus W Balters2, Devendra K Agrawal3
1Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE, 68178, USA.
Insights
Current anticoagulants cause bleeding. Targeting Factors IX, XI, and XII offers a safer strategy for preventing atherothrombosis and its associated ischemic events, addressing an unmet clinical need.
Area of Science:
- Cardiovascular Research
- Hematology
- Pharmacology
Background:
- Atherosclerosis causes significant cardiovascular and neurological ischemic events.
- Plaque rupture triggers coagulation, leading to thrombus formation and embolisms.
- Current antiplatelet and anticoagulant therapies, while reducing ischemic events, are associated with major bleeding risks.
Purpose of the Study:
- To review the limitations of existing anticoagulant therapies for atherothrombosis.
- To explore the potential of targeting coagulation Factors IX, XI, and XII as a safer anticoagulant strategy.
- To address the unmet need for improved therapeutic outcomes in preventing thromboembolic episodes.
Main Methods:
- Critical review of current literature on anticoagulant therapies.
- Analysis of clinical trial data comparing aspirin, rivaroxaban, and apixaban.
- Discussion of the role of Factors IX, XI, and XII in the coagulation cascade and atherothrombosis.
Main Results:
- Clinical trials show reduced ischemic events with newer anticoagulants but persistent bleeding issues.
- Targeting Factors IX, XI, and XII presents a promising avenue for developing more targeted anticoagulation.
- Existing therapies have limitations necessitating the exploration of novel targets.
Conclusions:
- There is a significant unmet need for anticoagulant therapies with improved safety profiles.
- Targeting Factors IX, XI, and XII holds potential for developing safer and more effective anticoagulant strategies in atherothrombosis.
- Further research into Factors IX, XI, and XII inhibition is warranted for improved patient outcomes.
Abstract:
Atherosclerosis is a leading cause of cardiovascular and neurological ischemic events. Plaque rupture leads to the exposure of highly thrombogenic material with blood and results in the activation of the coagulation cascade, thrombus formation, and embolic events. Although antiplatelets and anticoagulants are used to prevent thromboembolic episodes, bleeding episodes remain the major adverse effect. Decreased ischemic events have been reported while comparing oral rivaroxaban and apixaban with aspirin to improve the therapeutic outcome in several clinical trials, including Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 51, Apixaban for Prevention of Acute Ischemic and Safety Events, and GEMINI-ACS-1 phase II clinical trials. However, there were bleeding episodes. Thus, there is an unmet need for better therapeutic strategies. Therefore, the current focus is to target Factors IX, XI, and XII to develop safer and efficient strategies. In this article, we critically reviewed and discussed the limitations of current therapies and the potential of targeting Factors IX, XI, and XII for anticoagulant therapy in atherothrombosis.
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