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
Thrombomodulin
- 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