Haemostasis 11 Flashcards
Functions of haemostasis?
Prevention of bleeding from intact vessels and arrest of bleeding from injured vessels
Describe the main occurences in haemostasis?
1) vessel Injury
2) Vessel constriction
3) Formation of unstable platelet plug (platelet adhesion and aggregation)
4) Formation of stable platelet plug (blood coagulation)
5) Dissolution of clot and vessel repair (fibriolysis)`
What secretes Von Willebrand factor?
Endothelial cells and platelets
Define coagulation:
The process in which blood turns from a liquid to a solid state
How does platelet adhesion occur in homeostatic plug formation?
1) von willebrand factor binds to collagen in the exposed subendothelial layer and attracts platelets as they bind to the Glycoprotein 1b receptor on the von willebrand factor
2) Glycoprotein 1b receptors on the platelet bind directly to the collagen
How does platelet aggregation occur?
When the 1a or 1b receptor is activated, the platelt becomes activated. They release ADP and prostaglandins (thromboxane in particular) which activates other platelets and the 2b and 3 receptors on the platelets become available. Fibrinogen binds to multiple receptors pulling the platelets together. Thrombin is also generated which can activate the platelets.
What is the life span of a platelet?
8 days
Where are most clotting/fibrinolytic factors made?
Mainly the liver but endothelial cells and megakaryocytes produce Factor V
Describe the Intrinsic Pathways (clotting cascade):
1) Zymogen (Factor XII) is converted to Factor XIIa (active) which can convert Factor 11 to 11a. this converts 9 to 9a which activates 10 to 10a. Factor 8 is a cofactor that speeds up 9a converting 10 to 10a while it is converted to 8a.
Where do coagulation factors bind?
Onto activated phospholipids on the surface of platelets
Describe the extrinsic pathway:
Vessel damage releases tissue factor which is a potent initiator of the clotting cascade. This converts factor 7 to 7a which converts 10 to 10a. Tissue factor may also activate 9 to 9a when it activates 7.
Where do the intrinsic/extrinsic pathways meet and what occurs after?
At factor 10a. 10a converts prothrombin to thrombin
Describe the common pathway:
1) thrombin can further activate platelets causing a thrombin clot
2) Factor 5a helps factor 10a convert prothrombin to thrombin faster
3) Thrombin converts fibrinogen to fibrin causing a fibrin clot. (insoluble)
4) this can fibrin clot can be stabilised by factor 13a (via crosslinking) so its not moved b shearing forces
How would you describe tissue factor?
Physiological initiator of coagulation
What creates tissue Plasminogen Activateor (tPA)?
Endothelial Cells
