29 - Haemostasis Flashcards
Primary haemostasis
1)
2)
3)
1) Vasoconstriction
2) Platelet adhesion
3) Platelet aggregation
Occurs seconds to minutes after injury
Secondary haemostasis
1)
2)
1) Activation of coagulation factors
2) Formation of fibrin
Occurs minutes after injury
Fibrinolysis
1) Activation of fibrinolysis
2) Lysis of blood clot
Occurs minutes to hours after injury
Virchow’s triad
1)
2)
3)
Description of inappropriate clotting (thrombosis) Factors that can lead to thrombosis are: 1) Blood composition 2) Vessel wall 3) Blood flow
How is functional integrity of vascular wall tested?
It can’t be tested at the moment. No functional test
Coagulation system aspects
1)
2)
3)
1) Complex system of proteins in plasma
2) Interact with platelets and blood vessel wall
3) Clotting and bleeding are opposite ends of spectrum
Starter of the coagulation cascade
Tissue factor (TF) released by damaged epithelial cells
Key enzyme in coagulation cascade that must be controllled
Thrombin
Initiation phase of coagulation 1) 2) 3) 4)
1) Blood vessel wall injured, tissue factor is exposed.
2) TF binds FVIIa, or binds FVII and converts it to FVIIa
3) TF/FVIIa complex activates FIX and FX.
4) FXa binds to FVa on cell surface
Amplification phase of coagulation 1) 2) 3) 4)
1) FXa/FVa complex bound to endothelial wall converts small amounts of prothrombin to thrombin
2) Small amount of generated thrombin activates FV, FVIII, FXI and local platelets
3) FXIa converts FIX to FIXa (activated)
4) Activated platelets bind to FVa, FVIIIa, FIXa
Propagation phase of coagulation
1)
2)
3)
1) FXIIIa/FIXa complex on platelets activates FX on the surface of active platelets
2) FXa and FVa convert large amounts of prothrombin to thrombin in ‘thrombin burst’
3) Thrombin burst leads to stable formation of fibrin clot
Factors that convert prothrombin to thrombin
FXa and FVa in association with each other
Thrombin funciton
Converts fibrinogen to fibrin.
Activates platelets.
Can negatively-regulate upstream factors in coagulation cascade
Thrombin inactivation
Thrombomodulin-APC binds thrombin, regulates ability to cleave fibrinogen.
Irreversibly inhibited by antithrombin (process increased x1000 by heparin)
Non-coagulation roles of thrombin
1)
2)
3)
1) Activates protease-activated receptors (PARs)
2) Involved in angiogenesis, inflammation, atherosclerosis, neutrophil, monocyte migration
3) Could be involved in tumour spread