Physiological

Intrinsic Pathway

• initiated by factor XII and surface contact 

Extrinsic Pathway

• initiated by factor VIIa and tissue factor

Common Pathway

• two pathways meet at the common pathway
• both pathways generate factor Xa from X
• prothrombin converted to thrombin
• fibrinogen converted to fibrin

Formation of Thrombin :

• thrombin circulates in the inactive form
• formation of fibrin occurs in three phases
  • Proteolysis
    • protease enzyme thrombin cleaves fibrinogen resulting in a fibrin monomer, A and B fibrinopeptides
  • Polymerization
    • occurs spontaneously due to fibrin monomer
  • Stabilization
    • fibrin monomers are linked covalently by XIIIa into fibrin polymers, forming an insoluble fibrin clot

Feedback Inhibition :

• feedback inhibition limits enzymes’ ability to activate the coagulation pathways
• as thrombin increases, it destroys factors V and VIII
• factor Xa can prevent further activation of X by VIIa and tissue factor

Fibrinolysis :

• Fibrinolytic system
  • plasmin digests fibrin and fibrinogen and dissolves the clot
  • the presence or absence of hemorrhage or thrombosis depends on balance between the procoagulant and the fibrinolytic system
• Key components of the system include :
  • plasminogen
  • plasminogen activators
  • plasmin
  • fibrin
  • fibrin/FDP
  • inhibitors
    • plasma proteins that are natural anticoagulants
    • protease inhibitors
    • protein C pathway

Coagulation Cascade :

[create diagram]