Lecture 28

Question 1

How is blood clotting activated?

Answer 1

A cascade of zymogen activations

Question 2

What is a zymogen?

Answer 2

A zymogen is an inactive precursor molecule that is made active by the cleavage of one or more peptide bonds

Question 3

What are zymogens most often cleaved by for activation?

Answer 3

Serine proteases in the liver cleave zymogens for activation most often

Question 4

What is the function of platelets?

Answer 4

To migrate to the site of injury and aggregate with clotting factors to form a clot

Question 5

What are the main steps to the instrinsic pathway of blood clotting?

Answer 5

Kininogen + (kaloprine?) are released –> 12a –> 11a –> 9a –> 10a –> 2a (thrombin) –> 1a (fibrin) –> fibrin cross linking

Question 6

What are the assistant steps in the intrinsic pathway of blood clotting?

Answer 6

1) 8a assists 9a in converting 10 to 10a
2) 5a assists 10a in converting 2 to 2a (prothrombin to thrombin)
3) 13a assists 1a (fibrin) to form covalent cross-linking

Question 7

What activates the assistant steps in the intrinsic pathway of blood clotting?

Answer 7

Thrombin converts:

1) 8 to 8a
2) 5 to 5a
3) 13 to 13a
4) 7 to 7a

Question 8

What steps require calcium?

Answer 8

1) 9 to 9a
2) 10 to 10a
3) 2 to 2a
4) 7 to 7a
5) Cross-linking of fibrin fibers

Question 9

What factors require vitamin K to produce their inactive forms?

Answer 9

1) 9
2) 10
3) 2
4) 7

Question 10

What is the extrinsic pathway for blood clotting?

Answer 10

In the presence of tissue damage, a tissue factor can be activated to convert 7 to 7a (thrombin assists in this conversion). 7a can then convert 10 to 10a

Question 11

What does Vitamin K do to activate prothrombin?

Answer 11

Vitamin K adds a gamma carboxyl group to Prothromboglutamate, which attracts prothrombin to the platelet membrane where prothrombin is cleaved by proteases to form thrombin

Question 12

What inhibits vitamin K action?

Answer 12

Coumarins (Coumadin)

Question 13

What about fibrinogen makes it unsuitable for forming a clot?

Answer 13

It has a negative charge that keeps the molecule extended, however you want a compact molecule for a clot

Question 14

How exactly is fibrinogen activated to fibrin and how does it form cross links?

Answer 14

1) Fibrinogen contains 2 (A- alpha B- Beta and gamma) groups
2) Thrombin cleaves fibrinogen at arginine and glycine to release A- and B-
3) alpha, Beta, and gamma monomers then aggregate to form a clot

Question 15

How is the clotting cascade regulated?

Answer 15

1) Antithrombin 3 binds to thrombin and cleaves thrombin
2) Antithrombin 3 binds to 12a, 11a, 9a, and 10a
This prevents the clotting cascade from being activated when you don’t need it

Question 16

What does Heparin do?

Answer 16

Heparin enhances the action of antithrombin 3

Question 17

How are clots dissolved?

Answer 17

1) Kringle domain on the Tissue type Plasminogen Activation (TPA) binds to the clot
2) Serine domain cleaves plasminogen to plasmin
3) Plasmin dissolves the clot

Question 18

What are the steps to treating a patient having a heart attack?

Answer 18

1) Insert a stent to open any clogged arteries (may also use some heparin to prevent clotting)
2) Heparin is given through IV, whereas Lovonox only requires a local injection, making it an easier treatment option
3) Patient goes home on aspirin and plavix (inhibits platelet aggregation)

Question 19

What is given to treat an atrial fibrilation patient?

Answer 19

Coumadin

Question 20

What are new alternatives to coumadin?

Answer 20

1) Pradaxa - inhibits thrombin

2) Xarelto - inhibits 10a