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)

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References:

Goodman & Gilman's: The Pharmacologic Basis Of Therapeutics - 10th Edition - 2001. Chapter 55.