Haemostasis, Coagulation, Fibrinolysis

Master answer

Fibrinolysis

• Process by which fibrin clot is degraded to prevent excessive clot formation
• Plasminogen incorporated into clot
• Injured tissues and vascular endothelium gradually produce Tissue Plasminogen Activator (t-PA) in a delayed manner.
• Urokinase is produced by monocytes, macrophages and urinary epithelium
• Factor XII (Hageman factor) acts as a weak activator of plasminogen
• Plasminogen activated by t-PA, u-PA and factor XII to plasmin, a serine protease
• Plasmin cleaves fibrin into fibrin degradation products → reducing clot stability → Clot breakdown

Regulation of fibrinolysis

• Plasmin Activator Inhibitor (PAI) 1 & 2 – produced by vascular endothelium and inhibits tPA and uPA
• Protein C inactivates PAI, TAFI
• Thrombomodulin – expressed on in tact endothelium – binds thrombin and subsequently activates protein C
• Thrombin Activatable Fibrinolysis Inhibitor – produced by liver and cleaves plasmin binding sites on fibrin → decreased degradation
• α2 anti-plasmin – produced by liver, inhibits circulating plasmin, not fibrin bound plasmin

Sakurai 2016

Anti-Fibrinolytic Agents

• Aprotinin
  • Proteolytic enzyme inhibitor that acts on trypsin, plasmin and tissue kallikrein → forms reversible enzyme-inhibitor complex that inactivates free plasmin → ↓ clot lysis
• Tranexamic acid:
  • Competitive inhibition of plasminogen conversion to active plasmin → ↓ fibrin (clot) lysis
• Aminocaproic acid
  • Forms reversible complex with plasminogen → ↓ conversion to active plasmin → ↓ fibrin (clot) lysis

Sakurai 2016

Answer by Sakurai