Expansion
Antithrombin, protein C and S, and tissue factor pathway inhibitor
Expansion
Natural anticoagulants:
- Antithrombin: inhibits thrombin and factors Xa and IXa. Its activity is increased a thousandfold by heparin, which is how heparin works
- Protein C and protein S: thrombin bound to endothelial thrombomodulin activates protein C, which with protein S inactivates factors Va and VIIIa. Note that thrombin thereby switches from procoagulant to anticoagulant on intact endothelium
- Tissue factor pathway inhibitor: inhibits the tissue factor and factor VIIa complex
- Endothelial prostacyclin, nitric oxide and heparan sulphate
Inherited deficiencies cause thrombophilia:
- Factor V Leiden: the commonest, making factor V resistant to activated protein C
- Prothrombin gene mutation
- Antithrombin, protein C and protein S deficiency
Two clinical points: warfarin-induced skin necrosis occurs because proteins C and S have short half-lives and fall before the procoagulant factors, causing transient hypercoagulability, which is why heparin cover is given. And antithrombin deficiency causes apparent heparin resistance.