natural anticoagulants and fibrinolysis

  • Factors that prevent the initiation of thrombosis
    • Normal endothelium does not contain any clotting cascade activators (eg. TF)
    • Endothelial glycocalyx contains antithrombotic molecules:
      • Heparin-like oligosaccharides
      • Antithrombin-III
    • Blood flow produces shear stress which opposes regional clotting factor concentration and platelet aggregation
      • prevents blood from clotting

Factors that prevent primary haemostasis

  • Extrinsic pathway inhibitors:
    • Tissue factor pathway inhibitor (TFPI) antagonises the TF-FVIIa complex and prevents extrinsic pathway activation
  • Platelet activation/aggregation inhibitors:
    • Prostacyclin (PGI2), via GS-protein-coupled receptor
    • Nitric oxide (less iCa2+, also inhibits TXA2 receptor)
    • Fibrin degradation products (bind GPIIb/IIa receptors) 

Factors that prevent secondary haemostasis (intrinsic pathway)

  • Antithrombin III antagonises the activity of thrombin - target of heparin
    • function measured by APTT
  • Protein C (Vit K-activated)
    • Activated by thrombin
    • Inhibits thrombin, Factor Va and Factor VIIIa
  • Protein S: co-factor for Protein C
  • Thrombomodulin: co-factor for Protein C and S

Factors which promote fibrinolysis

  • Tissue plasminogen activator and urokinase activate plasminogen
    • tPA being ubiquitous on endothelium
  • Plasminogen is activated into p​​​​​​lasmin
  • Plasmin degrades fibrin into fibrin degradation products
  • alteplase works the same way

#haematology #coagulation