Hemostasis Introduction Part I

Question 1

What is the converging factor between the 2 pathways?

Answer 1

factor X

Question 2

Why is it called the extrinsic pathway?

Answer 2

requires tissue factor to function

Question 3

Why is it called the intrinsic pathway?

Answer 3

the components are contained w/I the plasma

Question 4

How is the extrinsic pathway initiated?

Answer 4

tissue factor binds to factor VIIa

Question 5

How is the intrinsic pathway initiated?

Answer 5

contact factors activate factor XI

Question 6

What are the contact factors?

Answer 6

factor XII, prekallikrein, HMWK

Question 7

What is the common pathway?

Answer 7

events after activation of factor X (the convergence)

Question 8

Extrinsic pathway steps?

Answer 8

tissue factor binds to factor VIIa, which activates factor X, Xa with cofactor Va activates factor II to IIa, which then converts fibrinogen to fibrin

Question 9

Intrinsic pathway steps?

Answer 9

activation of contact factors, leading to activation of factor XI, then with cofactor VIIIa, activation of factor X, then with cofactor Va, activate factor II, converting fibrinogen to fibrin, then activate factor X

Question 10

Where are the proteins of the coagulation cascade synthesized?

Answer 10

in the liver

Question 11

What is bleeding diathesis?

Answer 11

bleeding tendency or predisposition

Question 12

What are the exceptions to liver production of coagulation cascade proteins?

Answer 12

1. tissue factor (surface of many cells)

2. VWF (endothelial cells and megakaryocytes)

Question 13

Where is tissue factor synthesized?

Answer 13

on the surface of many cells

Question 14

Where is VWF synthesized?

Answer 14

endothelial cells and megakaryocytes

Question 15

Where is factor VIII produced?

Answer 15

the liver, spleen, lung, kidney

Question 16

What does the suffix “a” indicate?

Answer 16

the activated form

Question 17

Which factor has the shortest half life? Why is this important?

Answer 17

factor VII; it’s one of the first factor to deplete in disease

Question 18

Almost all of the enzymes in the coagulation cascade are _____.

Answer 18

serine proteases

Question 19

Inactive precursor proteins are called ____.

Answer 19

zymogens

Question 20

Zymogens that become active serine proteases include ____ (7).

Answer 20

1. factor XII (12)
2. prekallikrein
3. factor XI (11)
4. factor IX (9)
5. factor X (10)
6. factor VII (7)
7. factor II (2- prothrombin)

Question 21

Which are the vitamin-K dependent factors? (6)

Answer 21

1. factor II (2)
2. factor VII (7)
3. factor IX (9)
4. factor X (10)
5. anticoagulant protein C
6. protein S

Question 22

What to the vitamin-K dependent factors have in common?

Answer 22

Gla domains that bind Ca++ to cause conformational change of protein into active form

Question 23

Why is factor XIII (13) unique? What does it do?

Answer 23

enzyme that is not a serine protease- it’s a transglutaminase; covalently links fibrin molecules together to form a stable clot

Question 24

Why are cofactors important in the coagulation cascade?

Answer 24

they initiate and accelerate enzymatic rxns by bringing components together and orienting them correctly

Question 25

Name the cofactors in the coag. cascade. (4)

Answer 25

1. tissue factor
2. factor VIII (8)
3. factor V (5)
4. HMWK

Question 26

What protein makes the actual clot?

Answer 26

fibrinogen

Question 27

What does VWF stand for?

Answer 27

von Willebrand Factor

Question 28

What does VWF do?

Answer 28

it’s the carrier protein for factor VIII (8) in the plasma

Question 29

Where is VWF produced and stored?

Answer 29

Weibel-Palade bodies in endothelial cells and in alpha-granules of platelets

Question 30

Why does VWF bind to factor VIII (8)?

Answer 30

to protect it (prolong its half life)

Question 31

What happens in VWF-deficient pts?

Answer 31

low levels of circulating factor VIII (8), leading to a bleeding disorder similar to hemophilia A

Question 32

What do enzyme complexes consist of?

Answer 32

protease + cofactor + phospholipid surface + Ca++