Endogenous (Natural) Anti-Coagulants (Last Updated - 2/26/2005)
1) Prostaglandin I-2 (PGI-2 or Prostacyclin)
-synthesized by vascular endothelial cells
-inhibits thrombosis in intact vessels via inhibition of platelet aggregation & secretion
2) Anti-Thrombin
-inhibits coag factors of the intrinsic (IXa) & common (IIa & Xa) pathways
3) Heparan Sulfate
-synthesized by vascular endothelial cells
-stimulates anti-thrombin (similar to Heparin but to a much lesser extent)
4) Protein C
-plasma zymogen
-synthesized in liver (along with Protein S & Factors II (Prothrombin), VII, IX & X)
-its activation depends on calcium binding by its Gla (Gamma-Carboxyglutamate) residues
-once activated --> degrades Factors Va (Common Pathway) & VIIIa (Intrinsic Pathway)
-leads to decreased rates of activation of Factors X & II (Prothrombin) to activated Xa & IIa (Thrombin) --> anti-coagulation
-if deficient in Proteins C or S --> hypercoagulable state
5) Tissue Factor Pathway Inhibitor (TFPI or Extrinsic Pathway Inhibitor)
-found in lipoproteins
-binds to:
A) Factor Xa --> Inhibits it
B) Factor VIIa/Tissue Factor-complex --> Inhibits it
6) Even Thrombin (IIa) itself
-must be part of a counter-regulatory mechanism
-activates Protein C only in the presence of thrombomodulin (an integral membrane protein of vascular endothelial cells)
========================================================
References:
Goodman & Gilman's: The Pharmacologic Basis Of Therapeutics - 10th Edition - 2001. Chapter 55.