Coagulation cascade and Fibrinolysis Flashcards
What is tissue facotr?
Transmembrane protein
Where is TF located?
Plasma membrane of adventitial fibroblasts
Which blood clotting factor binds to TF?
VII
What does the TF/VIIa complex activate?
Clotting factors IX and X by proteolysis
What does the TF mechanism ensure?
Spatially constrained clotting at sites of vascular damage
What does the initial thrombin lead to?
Amplification of thrombin generation by activating factor XI, co-factor VIII and V and platelets
What is the enzymatic activity of Xa enhanced by?
Va
What does the assembley of IXa/VIIIA/X require?
Binding to platelet membranes
What is the fibrin clot dissolved by?
Plasmin
What is clot formation balanced by?
Clot degradation
What system balances clot formation and clot degradation?
Fibrinolytic system
What proenzyme does plasma contain?
plasminogen
What 2 things does plasminogen bind to?
Fibrin and to cell surfaces
What do plasminogen activators convert plasminogen to?
Enzymatically active plasmin
What is plasmin?
Serine protease that digests fibrinogen and fibrin thereby dissolving clot
What do endothelial cells continuously release?
Tissue plasminogen activator (tPA)
How is tPA activated?
Binding to fibrin clots
What is tPA’s major substrate?
Plasminogen
What does partial degradation of fibrin by plasmin expose?
Further tPA binding sites on fibrin and plasmin activates tPA slightly by proteolysis
What does tPA binding to fibrin initiate?
Local activation of fibrinolysis
What are plasminogen activator inhibitors?
Serine protease inhibitors that block function of tPA
Define thrombosis.
Clot formation inside vessels
Where does venous thrombosis occur?
Lower limbs
How do thrombus fragments reach the heart?
Carried by bloodstream through right heart into pulmonary arteries
What do thrombus fragments cause?
Occlude blood flow through the lung leading to immediate sudden death
What do arterial thrombosis lead to?
Local tissue damage depending on artery/organ
