The Blood Coagulation And Fibrinolytic Systems: Amplification And Feedback Flashcards
Which protein is most responsible for amplification in the coagulation cascade
Thrombin
Describe the positive feedback that thrombin fascilitates
Thrombin activates factor 5 into its active form, as well as factor 8 and factor 11, hence amplifing it’s own production via the intrinsic pathway
What is the name of factor 13?
Transglutaminase
What is the role of factor 13?
To stabilise the fibrin mesh
What activates factor 13 and prepares it’s substrate?
Thrombin. Activates factor 13 and converts fibrinogen to fibrin
What type of proteins are tPA and uPA? What is their role
They are serine proteases. They work in the anticoagulant system to dissolve the clot (fibrinolysis)
How are tPA and uPA activated?
By cleavage into a two-chain form (although tPA is considerably active even in single chain form).
They are cleaved by Factor 10a, Kallikrein and plasmin (positive feedback on plasmin activation)
Which reaction does tPA and uPA catalyse?
The conversion of plasminogen into plasmin
Describe the enzymatic regulation of clotting through thrombin and protein C
Enzymatic regulation occurs through thrombin, which binds its receptor thrombomodulin. This complex activates protein C (a serine protease) which forms a complex with protein S and degrades the active forms of factor 5 and 8
Describe thrombin’s enzymatic regulation of fibrinolysis
Thrombin-thrombomodulin complex can also activate the thrombin-active fibrinolytic inhibitor (a carboxypeptidase) which cleaves the C-terminals of fibrin meshwork so that plasmin is unable to degrade the fibrin mesh
How does non-enzymatic control of the clotting/fibrinolytic system occur?
Via serpins (serine protease inhibitors), which inhibit either the formation of factor 10a the formation of active tPA and uPA and plasmin formation Or through kunitz type inhibitors
