What is antithrombin (AT)?

By William Aird

A serine protease inhibitor (serpin) and natural anticoagulant:

  • Physiologically inactivates
    • Thrombin (factor IIa)
    • Factor Xa (FXa)
    • To a lesser extent:
      • Factor IXa
      • FXIa
      • FXIIa
      • Tissue plasminogen activator (t-PA)
      • Urokinase
      • Trypsin
      • Plasmin
      • Kallikrein
  • Alpha2-globulin synthesized predominantly in the liver
  • Molecular weight of 58,200 Da
  • Half-life of approximately 2.4 days
  • Anticoagulant effect of AT is accelerated at least a thousand times in the presence of heparin (heparin is a co-factor):
    • Requires the binding of a unique sequence-specific pentasaccharide domain of heparin to the heparin-binding domain of AT.
    • This interaction induces a conformational change in AT, which accelerates the inhibition of FXa.
    • The inhibition of thrombin, in addition, requires heparin to bind to both AT and thrombin, to form a ternary bridging complex, so that then thrombin can be inhibited.
  • In addition to its anticoagulant role, AT has been found to have an important anti-inflammatory effect that occurs in relation to its interaction with the endothelium.

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