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.
What is the treatment of choice for a 65-year-old woman with a history of TIA's, who has stenosis of the internal carotid artery and intimal plaque seen on the carotid Doppler?
Extra info: TIAs are caused by platelet emboli so aspirin is the treatment of choice.
What is the treatment of choice for a 40-year-old man newly admitted with an acute pulmonary embolism 14 days after fracturing his femur?
Extra info: The man will get acenocoumarol, but needs therapy with heparin first. Clinical trials show LMWH to be superior to unfractioned heparin, so that would be the choice.