last updated 13-10-2021


Anticoagulation and antithrombogenic factors

Thrombin formation is downregulated by several mechanisms.

  • The tissue factor pathway inhibitor (TFPI) inhibits the activity of the TF-factor VIIa-complex.
  • Activated Protein C (APC) with Protein S as cofactor inactivates the activated cofactors Va and VIIIa. APC is formed from Protein C at the endothelial surface by the thrombin-thrombomodulin complex.
  • Factor Xa and thrombin are inhibited by antithrombin (AT). Heparin acts as a cofactor of this reaction.
  • Prostacyclin (PGI2) which is released by the endothelium inhibits platelet activation.


In vivo, fibrin formation is regulated by thrombin formation (balance between procoagulant and anticoagulant reactions) while fibrinolysis is regulated by plasmin formation (balance between profibrinolytic and antifibrinolytic reactions).

TFPI = tissue factor pathway inhibitor
TF = tissue factor
NO = nitric oxide
PGI2 = prostacyclin
PC = protein C
APC = activated protein C
TM = thrombomodulin
IIa = thrombin
AT = antithrombin

The graphic below shows the different drugs involved in anticoagulation.


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