Week 9

Question 1

What is the simple coagulation cascade?

Answer 1

Damaged blood vessel releases clotting factors, which cause prothrombin to form thrombin, meanwhile activated platelet attracts others forming a plug, Thrombin causes Fibrinogen to form fibrin, of which adheres the plug.

Question 2

When is the intrinsic pathway activated?

Answer 2

Linked to changes in the phospholipid membrane of all the cells.

Question 3

When is the extrinsic pathway activated?

Answer 3

Though the injury of cells. Releasing tissue factor

Question 4

What does both pathways activate?

Answer 4

Factor 10 and factor 5 which form a complex which processes prothrombin into thrombin.

Question 5

What is prothrombin and what does its active form do?

Answer 5

Is the inactive form of thrombin which is always circulating, which forms fibrin.

Question 6

What does fibrin do?

Answer 6

Keeps the planets stuck together and with the endothelium.

Question 7

What are enzymes called that need to be activated, of which always circulate in the body?

Answer 7

Zymogens, which are in there zymogenic form

Question 8

What is Atherothrombosis?

Answer 8

Is associated with an atherthroscerotic plaque in the blood vessels, which is formed of macrophages and other cells and lipids.

Question 9

What happens when there is too low activation of platelets and coagulation?

Answer 9

Bleeding, leading to bleeding Diathesis

Question 10

What happens when there is over activation of platelets and coagulation?

Answer 10

Clotting, leading to coagulation and thrombophilia

Question 11

What is the mechanism of action of Warfarin?

Answer 11

It antagonises the antihemorrhagic effect of vitamin K, inhibiting vitamin K dependent coagulation factors II, VII, IX, and X, by inhibiting vitamin K reductase, preventing vitamin K from being reduced to its active form.

Question 12

How does activated reduced vitamin K affect the coagulation cascade?

Answer 12

It would activate prothrombin from its unactivated form.

Question 13

What aspect of coagulation does warfarin effect?

Answer 13

It inhibits the vitamin K reductase, which inhibits production of activated vitamin K, inhibiting the activation of coagulation factors

Question 14

What is the clinical use of Warfarin?

Answer 14

For treatment:

• Venous thrombosis and its extension pulmonary embolism.
• Thromboembolic complications associated with atrial fibrillation and/or cardiac vale replacement.
• Reduce risk or myocardial infarction and stroke

Question 15

What are the different enzymes with eliminate S and R Warfarin to its inactive form?

Answer 15

S -Warfarin
- CYP2C9
R -Warfarin
- CYP1A1 
- CYP1A2
- CYP3A4

Question 16

Which enantiomer of warfarin works better and why?

Answer 16

S -Warfarin because it binds better to the Vitamin K reductase receptor

Question 17

What happens when someone has overactive CYP2C9?

Answer 17

S-Warfarin forms its inactive metabolites more quickly leading to less exposure of the drug, so the patients would need a higher dose of the drug, opposite when under-active

Question 18

What are the different polymorphisms of CYP2C9 and the effects on warfarin?

Answer 18

• 1 - Associated higher activity, need a higher dose.
• 2 - Associated with medium activity
• 3 - Associated with lower activity, need a lower dose

Question 19

How much does genetic polymorphisms account for, within an individuals variation in dose responsiveness?

Answer 19

50%

Question 20

How can you test if someone will respond well to warfarin?

Answer 20

Take a sample of blood stimulate separate the plasma and stimulate the formation of fibrin in vitro, measure how long it takes for the fibrin clot to form, through both pathways.