Blood Clotting

Question 1

What is hemostasis?

Answer 1

Hemostasis – maintaining volume of blood

Question 2

What is the normal state of the blood vessel wall?

Answer 2

Anti-thrombogenic

Question 3

What happens after blood vessel is damaged? (brief)

Answer 3

Vessel damage exposes underlying
tissue – platelets can adhere and are
activated
Activated platelets release factors to
activate other platelets that adhere to
the wound
Coagulation factors are activated
Fibrinogen is converted to fibrin –
assembles meshlike structure to
support the clot

Question 4

How is blood clotting speed ensured?

Answer 4

Factors are always in blood, but inactive

Question 5

What are platelets?

Answer 5

Fragments of cells in
the blood (made by
megakaryocytes in bone
marrow)

Question 6

What do platelets do?

Answer 6

Vessel damage -> platelet
activation – adhere and plug hole,
release factors to promote clotting

Question 7

What is the normal state of platelets?

Answer 7

Platelet adhesion is regulated – normal is “non-sticky” and activated is
“sticky”

Question 8

How are platelets activated?

Answer 8

Activated platelets release ADP and produce thromboxane A2
to activate
more platelets

Question 9

How does aspirin prevent clotting?

Answer 9

Inhibit enzymes involved in synthesis of thromboxane A2 from arachidonic acid (via prostaglandin)

Question 10

What is the descriptive name of factor I? What is its function?

Answer 10

fibrinogen

forms fibrin

Question 11

What is the descriptive name of factor II? What is its function?

Answer 11

prothrombin

serine protease

Question 12

What is the descriptive name of factor III? What is its function?

Answer 12

tissue factor

receptor/co-factor

Question 13

What is the descriptive name of factor IV? What is its function?

Answer 13

Ca2+

cofactor

Question 14

Which factors are serine proteases?

Answer 14

II, VII, IX, X, XI, XII, pre-kallikrein

Question 15

What is the function of factor XIII?

Answer 15

Ca2+ dependent transglutaminase

Question 16

What is the function of factors IV, V, VIII, HMW kininogen?

Answer 16

cofactor

Question 17

How many factors are there?

Answer 17

15

Factors I - XIII, pre-kallikrein, and HMW kininogen

Question 18

What name change occurs when a factor is activated?

Answer 18

When clotting factors are activated, their name

changes – e.g. X becomes Xa

Question 19

What are the steps in the extrinsic pathway cascade?

Answer 19

1) VII is activated to VIIa (catalyzed by III [tissue factor], phospholipase, and Ca2+)
2) VIIa catalyzes activation of X -> Xa

Question 20

What are the steps in the intrinsic pathway?

Answer 20

1) In damaged tissue, pre-kallikrein converted to kallikrein
2) kallikrein catalyzes conversion of XII to XIIa
3) XIIa catalyzes conversion of XI to XIa
4) XIa catalyzes conversion of IX to IXa
5) IXa combines with VIIIa, and then catalyzes the conversion of X -> Xa

Question 21

What is the common product of the extrinsic and intrinsic pathways?

Answer 21

Factor Xa

Question 22

What are the steps in the common pathway?

Answer 22

1) Factor V is activated to Va
2) Va and Xa combine to activate II to IIa (prothrombin to thrombin)
3a) Thrombin (IIa) catalyzes activation of I (fibrinogen) to Ia (fibrin)
3b) Thrombin cleaves zymogens in intrinsic and extrinsic pathways
3c) Thrombin catalyzes activation of XIII to XIIIa
4) Fibrin (Ia) causes formation of a crosslinked clot

Question 23

What is the purpose of the factor cascade?

Answer 23

Signal amplification

Question 24

What is carboxylation? What amino acid does it commonly occur on in the context of clotting?

Answer 24

Posttranslational addition of carboxyl group

Often on Glu

Question 25

Why is carboxylation important for clotting?

Answer 25

Factors VII, IX, and X require Ca2+

Carboxylation allows these factors to interact with Ca2+

Question 26

Why is vitamin K important for clotting?

Answer 26

Necessary for carboxylation of Glu to Gla

1) Glu + vitK -> Gla + vitK-epoxide (via vitK carboxylase)

2) VitK must be regenerated, so…
vitK-epoxide -> vitK (via vit K reductases)

Question 27

How does warfarin prevent clotting?

Answer 27

Inhibits vitK reductases, preventing regeneration of vitK

Question 28

How is fibrin produced? What does it do? What is its structure?

Answer 28

Fibrinogen – hexamer – 2Aa, 2Bb and 2g chains -soluble

Thrombin cleaves fibrinogen to fibrin – removes
small peptides from the a and b chains – fibrin
molecules can now polymerize

Question 29

Which factor crosslinks fibrin?

Answer 29

XIIIa

Question 30

What is factor XIIIa? How does it work?

Answer 30

Transglutaminase

Crosslinks by forming isopeptide bond
between lysine and glutamine residues

Question 31

What causes hemophilia?

Answer 31

Deficiency of clotting factors?

Question 32

What are the 2 main types of hemophilia?

Answer 32

in US 80% have defective VIII – X-linked

in US 20% have defective IX

Question 33

What causes Glanzman’s thrombasthenia?

Answer 33

Platelet defect or deficiency

Question 34

What are the steps in turning off clotting?

Answer 34

Called anti-coagulation phase
1. Diffusion of factors away from wound
2. Protein C – a protease that degrades Va
and VIIIa
• Activated by thrombin
3. Serpins – serine protease inhibitors
• Antithrombin III (AT3) – in blood – inhibits thrombin and
other clotting factors – heparin dramatically enhances
inhibition of thrombin and Xa

Question 35

How are blood clots removed?

Answer 35

Fibrinolysis
1. Plasmin – protease that degrades fibrin
2. Plasminogen – inactive precursor to plasmin
– binds to fibrin (in the clot)
3. Plasminogen – activated by protease – tissue
plasminogen activator (tPA)
4. tPA released from vessel wall