Pharmacology 2.14

Question 1

What are the four events which occur in hemostasis?

Answer 1

1) vasoconstriction
2) platele actions: adhesion, activation, release/secretion, aggregation
3) fibrin clot formation/coagulation
4) fibrinolysis

Question 2

What is hemostasis?

Answer 2

process of normal blood clotting, subsuquent dissolution of the clot, and subsuquent repair of the injured tissue

Question 3

What are the major components of the hemostatic system?

Answer 3

• vascular endothelium
• platelets
• coagulation system
• fibrinolytic system

Question 4

What are the functions of the endothelial cell lining as it pertains to hemostasis?

Answer 4

thrombo-resistant by:

1) physical barrier btwn circulating platelets & clotting factors and thrombogenic subendothelial substances (collagen, tissue factor)
2) endothelial production of 2 potent vasodilators and inhibitors of platelet function: prostaglandin I2, PG12; nitric oxide NO)

Question 5

Which molecule activates fibrinolysis to inhibit thrombosis?

Answer 5

t-PA, a protease; tissue plasminogen activator

Question 6

Which molecules inhibit platelet aggregation to inhibit thrombosis?

Answer 6

PGI2

NO

Question 7

What are the events which occur in the Common Pathway of coagulation cascade?

Answer 7

1) prothrombin is converted to thrombin

2) thrombin converts to fibrinogen to fibrin

Question 8

What are the events which occur in primary hemostasis?

Answer 8

formation of a platelet plug

Question 9

What are the events which occur in secondary hemostasis?

Answer 9

formation of a fibrin clot

Question 10

What are the events which occur in platelet adhesion?

Answer 10

Platelet receptors GP1a-IIa and GP VI bind directly to subendothelial collagen

Platelets bind indirectly to collagen via GPIb to von Willebrand factor (vWF) secreted by endothelial cells

Question 11

What are the events which occur in activation?

Answer 11

• platelet adhesion stimulates their activation!
• releases TXA2
• express Gp IIb/IIIa receptor which will bind to collagen

Question 12

What are the events which occur in aggregation?

Answer 12

1) vWF binds to collagen
2) platelets bind to vWF
3) platelets release ADP, TXA2
4) fibrin clot mesh forms within platelets

Question 13

What is the function of vWF

Answer 13

secreted by endothelial cells; platelets bind indirectly to collagen via GPlb to vWF during platelet adhesion

Question 14

What is the function of ADP

Answer 14

released by platelets and promote platelet aggregation by activating other platelets

Question 15

What is the function of TXA2?

Answer 15

vasoconstrictor which promotes platelet aggregation and thrombosis + hemostasis; released by platelet

Question 16

What is the function of thrombin?

Answer 16

blood clotting factor; activated zymogen (enzyme)

Question 17

What is the function of Gp IIB/IIIA?

Answer 17

platelet receptors (on actual platelet and expressed when platelet is activated) which bind to collagen and allow them to form the clot

Question 18

What is the function of fibrinogen?

Answer 18

blood clotting factor which allows adjacent platelets to bind to one another during clot formation

Question 19

What is the funciton of prostacyclin?

Answer 19

vasodilator which inhibits platelet function; released by endothelial cell

Question 20

What is the function of nitric oxide?

Answer 20

vasodilator which inhibits platelet function

Question 21

What is the activation of the fibrinolytic system?

Answer 21

1) t-PA (tissue plasminogen activator) is released by endothelial cells and binds to plasminogen and activates it to:
2) plasmin which causes fibrin clot to degrade and release FDP (fibrin degradation products)

Question 22

What is the inactivation of the fibrinolytic system?

Answer 22

1) PAI (plasminogen activator inhibitor) binds up t-PA so it can not longer promote fibrinolysis
2) Even if plasminogen is converted to its active form (plasmin) there are plasmin inhibitors which will bind to plasmin to keep its degradation activity in check