Factors IX, XI, and XII: potential therapeutic targets for anticoagulant therapy in atherothrombosis

Rev Cardiovasc Med. 2019 Dec 30;20(4):245-253. doi: 10.31083/j.rcm.2019.04.56.


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.

Keywords: Atherothrombosis; atherosclerotic plaque; blood coagulation; factor IX, XI, and XII inhibition; plaque rupture.

Publication types

  • Review

MeSH terms

  • Animals
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Atherosclerosis / blood
  • Atherosclerosis / diagnosis
  • Atherosclerosis / drug therapy*
  • Blood Coagulation / drug effects*
  • Factor IX / antagonists & inhibitors*
  • Factor IX / metabolism
  • Factor XI / antagonists & inhibitors*
  • Factor XI / metabolism
  • Factor XII / antagonists & inhibitors*
  • Factor XII / metabolism
  • Hemorrhage / chemically induced
  • Humans
  • Molecular Targeted Therapy
  • Plaque, Atherosclerotic
  • Risk Factors
  • Thrombosis / blood
  • Thrombosis / diagnosis
  • Thrombosis / drug therapy*
  • Treatment Outcome


  • Anticoagulants
  • Factor IX
  • Factor XII
  • Factor XI