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Targeting factor Xa and thrombin: impact on coagulation and beyond
1Dr. Charles Esmon, PhD, Howard Hughes Medical Institute, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA, Tel.: +1 405 271 7571, Fax: +1 405 271 2870,
Thrombosis and Haemostasis
|December 17, 2013
Summary
Factor Xa and thrombin, beyond anticoagulation, influence inflammation and atherothrombosis. Direct inhibition of these factors shows anti-inflammatory effects and plaque stabilization, impacting cardiovascular health.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Pharmacology
Background:
- The hemostatic system and thrombus formation are increasingly understood.
- Factor Xa and thrombin (factor IIa) are key anticoagulants.
- Emerging evidence links these factors to non-hemostatic roles, including inflammation.
Purpose of the Study:
- To summarize the non-hemostatic activities of factor Xa and thrombin.
- To review the effects of direct factor Xa or thrombin inhibition on these activities.
- To explore the roles of factor Xa and thrombin in atherosclerosis and atherothrombosis.
Main Methods:
- Review of preclinical and clinical studies.
- Analysis of proteinase-activated receptor signaling.
- Discussion of cardiovascular outcomes from Phase III trials.
Main Results:
- Non-hemostatic activities of factor Xa and thrombin are mediated via proteinase-activated receptors.
- Direct inhibition of factor Xa or thrombin demonstrates anti-inflammatory effects.
- Preclinical data suggest plaque stabilization and improved cardiovascular profiles with direct inhibitors.
Conclusions:
- Factor Xa and thrombin possess significant non-hemostatic functions.
- Direct inhibition offers therapeutic potential beyond anticoagulation.
- Rivaroxaban, apixaban, and dabigatran etexilate show promise in managing atherothrombosis.
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