Coagulation Flashcards
What is the main function of vascular system in coagulation
Constriction of vasculature serves to reduce blood flow at the site of injury to prevent blood loss
- Vasoconstriction slows the flow of platelets passing by the injury, allowing them to have a better chance of ahering
What is the main function of the Platelet system in coagulation
Act to prevent blood loss by forming platelets plugs at the injury site.
- platelets also release factors that can induce vasoconstriction
- platelets also secrete factor V and providing phospholipids needed by coagulation factors
what is the main function of the coagulation system
to form fibrin clots and to further stimulate platelet activation by producing thrombin
What is the main function of the anti-coagulation system in coagulation
to reduce coagulation by reducing thrombin formation and destroying thrombin that is already formed
What is the main function of fibrinolysis system in coagulation
to dissolve unnecessary clots formed in undamaged tissues and to remove clots after the injury has healed
What are the Three glycoprotein ligands and what do they bind
GPIb-alpha binds Willebrand factor on ECM
- Initial tether of platelets
GPVI binds collagen
- Initial activation of platelets (release platelet activators)
CPIIa/IIIb binds fibrinogen
- facilitates platelet-platelet interactions
What are the three G protein coupled receptor ligands and what do they bind
P2Y12 activated by ADP
Protease activated receptor (PAR) activated by Thrombin
Thromboxan A2 receptor activated by thromboxan A2
What are the functions of platelet secreted ADP, Serotonin and thromboxane A2
ADP = further activates platelets
Serotonin = further activate platelets and the cause vasoconstriction
Thromboxane A2 = activate platelets and cause vasoconstriction
What is the function of Prostacyclin (PFI2)
It is formed and released by vascular endothelial cells and functions to INDUCE vasodilation and INHIBIT platelet adhesion and activation
What role do platelets play in coagulation cascade
- Provide phospholipids that are used by coagulation factors
- Secrete factor V
How does thrombin activate platelets
Thrombin activates platelets by activatin the protease activated receptors (PARs) on the surface of platelets
- PARs are G protein coupled receptors
What coagulation factors require viatmin K for proper activity
Factors II, VII, IX as well as proteins S, C and Z
Vitamin K was born in 1972 (10, 9, 7, 2)
What is the mechanism by which heparin sulphate or heparin regulates thrombin and factor Xa degradation
Heparin binds to antithrombin III (AT) and activates it. AT is an enzyme inhibitor that INACTIVATES thrombin and factor Xa, preventing coagulation initation
describe the mechanism by which thrombin/thrombomodulin complex reduces coagulation
complex binds to and activates protein C, a serine protease
- activated protein C (APC) interacts with protein S and the complex INACTIVATES factors Va and VIIIa
Why does Factor V Leiden mutation lead to hypercoagulable state
the mutated factor V cannot be deactivated by APC
How does Plasminogen regulate fibrinolysis
plasminogen: zymogen that is converted into plasmin (initiation of fibrinolysis)
how does Plasmin regulate fibrinolysis
Plasmin: active serine protease that can cleave fibin, thereby dissolving clots
How does tPA regulate fibinolysis
Activates plasminogen
How does PAI regulate fibinolysis
removal and deactivation of tPA to prevent removal of necessary fibrin clots
How does alpha2-plasmin inhibitor regulate fibrinolysis
inhibits plasmin that is NOT already bound to fibrin in effect to negatively regulate the fibrinolytic system
Describe the extrinsive pathway
1) damage exposes tissue factor III
2) factor III activates Factor VII
3) activated Factor III, VII and Ca2+ activate Factor X
4) Factor X slowly forms Thrombin from Prothrombin with Ca2+ and Phospholipids
5) Once some Thrombin is made, Thrombin activates Factor V
6) Factor Xa and Factor Va form a prothrombin activator complex that is ALOT FASTER AT turning Prothrombin into Thrombin
Describe the Intrinsic Pathway
1) Factor XII is activated by exposure to Collagen
2) Factor XIIa + Ca activates Factor XI
3) Factor XIa + Ca activates Factor IX
4) Factor IXa activates Factor X
5) Factor Xa + Ca + Phospholipids SLOWLY converts Prothrombin into Thrombin
6) Once a LITTLE THROMBIN is made, Thrombin activates Factor VIII
7) Factor VIIIa + Factor IXa + Ca + Phospholipids FORM the TENASE COMPLEX
8) TENASE COMPLEX causes activation of Factor X and RAPID PRODUCTION OF THROMBIN
