Q1iv / 15B19: Describe the fibrinolytic pathway and identify areas of interaction with the coagulation pathway

15B19: Exam Report

Describe the fibrinolytic pathway and identify areas of interaction with the coagulation pathway (80% of marks). List two anti-fibrinolytic agents and state their specific mechanism of action (20% of marks).

8% of candidates passed this question.

The fibrinolytic pathway is a cascade largely made up of proteolytic enzmes and other factors synthesized in the liver that circulate in inactive precursor forms. Marks were awarded for description of the principal members of the cascade and the pathway relations between them. Endothelium is also important in the fibrinolytic pathway.

Regulation of the pathway to localise the site and size of clot as well as delayed onset of action of fibrinolysis is central to any description. Regulation of fibrinolysis by the coagulation cascade and a description of this area of interaction were expected.

Many candidates provided a reasonable description of the fibrinolytic cascade. Marks were not awarded for description of the coagulation cascade that did not have relevance to fibrinolysis. Understanding of regulation of fibrinolysis and it’s interaction with coagulation was poorly answered.

Most candidates were able to name two antifibrinolytic agents. Few were able to describe mechanism of action.

Q1iv / 15B19: Describe the fibrinolytic pathway and identify areas of interaction with the coagulation pathway (80 marks). List two anti-fibrinolytic agents and state their specific mechanism of action (20 marks)

Fibrinolysis

The enzymatic dissolution of fibrin to restore blood flow and prevent to propagation of clots

Fibrinolysis

  • Contains clot formation & restores blood flow
  • Both fibrin & fibrinogen bind PLASMINOGEN
  • Plasminogen = proenzyme synthesised in the liver
  • Plasminogen structured into clot interior – cannot solitarily fibrinolyse
  • Plasminogen activators (Urokinase, tPA) are produced by endothelial cells
  • Diffuse from Endothelial Cells
  • Catalyse PLASMINOGEN → PLASMIN
Fibrin

Regulation

  • Activators
    • tPA
    • UrokinasePA
  • Inhibitors
    • Plasmin in circulation metabolised by:
      • A2 antiplasmin
      • Plasminogen Activator Inhibitor

Anti-Fibrinolytics

Aminocaproic Acid

  • Binds the kringle domain of plasminogen (REVERSIBLE)
  • Blocks plasminogen binding to fibrin
  • ∴stops fibrinolysis

Tranexamic Acid

  • Binds plasminogen lysine binding sites (REVERSIBLE)
  • Competitively inhibits activation of plasminogen → plasmin
  • ∴stops fibrinolysis
  • 10 x stronger than aminocaproeic acid
  • At v. high doses inhibits PLASMIN
Plaminogen