Q1v: Describe the mechanisms of preventing thrombosis including endothelial factors & natural anticoagulants

Regulation of Coagulation

  • Clots prevent blood loss from damaged vessels
  • Intact vessels don’t clot due to:
    • Intact endothelium
    • Blood flow washing away & diluting active mediators
    • Coagulation factors circulating in inactive form
    • Inhibitory systems

Intact Endothelium

  • No collagen/tissue factor exposure
  • Glycocalyx repels platelets
  • PROSTACYCLIN = ↑cAMP →inhibits platelet aggregation & relaxes smooth m.
  • NO →inhibits platelet aggregation & relaxes smooth m.
  • Produces THROMBOMODULIN →which activates protein C
  • Produces Heparin sulphate →enhances AIII activity
  • Low basal secretion of TISSUE PLASMINOGEN ACTIVATOR →to promote fibrinolysis

Blood Flow/Wash Away

  • Large SA endothelium →constant repair
  • ∴basal platelet & coag factor consumption
  • Blood flow limits build up of nature factors

Inactive Coag Factors

  • Key factors of coagulation are membrane bound to platelets/endothelium
  • Most factors circulate in plasma inactive

Inhibitory Systems

Tissue factor pathway inhibitor

  • Inhibits TF – VIIa/Xa complex downstream from injury

Heparin sulphate – AT III

  • Neutralises free Xa & thrombin


  • A protein on Endothelial cells
  • Co-factor for thrombin
  • But ∆thrombin from PROCOAG →ANTICOAG
  • Thrombin bound THROMBOMODULIN →activates Protein C

Protein C

  • Anti-inflammatory
  • Cytoprotective
  • Anticoagulant
  • Maintains permeability of blood vessels

Fibrinolytic System

  • Any initiation of clotting also activates fibrinolysis
  • Plasminogen/plasmin built into clots →preferentially activated by fibrinolysis activators