Coagulation Cascade - Brar

Question 1

What are the 4 major players in forming a clot?

Answer 1

1. Endothelial Cells
2. Subendothelial Cells
3. Platelets
4. Clotting factors

Question 2

Endothelial cells have what affect on blood clotting?

Answer 2

Inhits it

Question 3

Endothelial cells inhibit blood clotting by forming what, which inhibits platelet adhesion & aggregation?

Answer 3

Prostacyclin

Question 4

Platelets release what after they bind to subendothelial tissue?

Answer 4

1. Protiens

2. Vasoactive amines

Question 5

Plasma protiens which create a proteolytic cascade which ends with the production of insoluble firbrin from soluble fibrinogen are called what?

Answer 5

Clotting factors

Question 6

What mediates platelet adhesion to exposed extracellular matrix when the endothelial lining of blood vessel is damaged?

Answer 6

von Willebrand Factor (vWF)

Question 7

vWF is a protein that is present where?

Answer 7

1. Plasma

2. Extra cellular matrix

Question 8

vWF binds to what?

Answer 8

1. A receptor on the platelet membrane

2. Collagen fibers in the tissue

Question 9

Adhered platelets by agents that increase the calcium concentration of platelets, which is typically what 2 agents?

Answer 9

1. Thrombin

2. Thromboxane

Question 10

During activation, a receptor for what becomes exposed on the platelet membrane?

Answer 10

Fibrinogen

Question 11

Fibrinogen binds to a receptor exposed on the platelet membrane and causes what?

Answer 11

Platelet aggregation

Question 12

Fibrinogen consists of how many pairs of polypeptides?

Answer 12

3

Question 13

Fibrinogen is the precursor for what?

Answer 13

Fibrin

Question 14

What converts fibrinogen into fibrin?

Answer 14

Protease thrombin

Question 15

Why is fibrinogen more soluble than fibrin?

Answer 15

The fibropeptides are covered in negatively charged aspartate & glutamate residues (repel eachother)

Question 16

The negative charges on fibrinopeptides help prevent what?

Answer 16

Aggregation

Question 17

The crosslinking of fibrin is catalyzed by what?

Answer 17

Transglutaminase (factor XIII)

Question 18

Thrombin formation is limited to where?

Answer 18

The site of injury

Question 19

Thrombin is produced from prothrombin vi what?

Answer 19

Factor X a

Question 20

The formation of Thrombin produces what other product?

Answer 20

A catalytically inactive fragment

Question 21

The catalytically inactive fragment produced with thrombin has 10 residues of what?

Answer 21

Gamma- carboxyglutamate

Question 22

Gamma- carboxyglutamates are produced by hepatocytes in a reaction requiring what?

Answer 22

Vitamin K

Question 23

What is the only protease in the extrinsic pathway?

Answer 23

Factor VII a

Question 24

Factor VIIa is only active in the presence what?

Answer 24

Tissue factor

Question 25

Tissue factor is a membrane glycoprotein exposed after what?

Answer 25

Injury of the blood vessel

Question 26

The intrinsic pathway requires what to activate?

Answer 26

a negatively charged surface (ex. glass or phospholipid membrane)

Question 27

What are the initiating reactions of the intrinsic pathway?

Answer 27

Contact phase activation

Question 28

The contact phase activation requires what two proteases?

Answer 28

1. Kallikrein | 2. Factor XIIa

Question 29

The contact phase activation requires which activator protein?

Answer 29

High Molecular Weight Kininogen (HMWK)

Question 30

Factor IXa activates Factor X, this step requires what?

Answer 30

Factor VIIIa

Question 31

Which clotting factors are vitamin K dependent?

Answer 31

1. Prothrombin (II) 2. Factor X 3. Factor VII 4. Factor IX

Question 32

Which factors are Heparin inhibited?

Answer 32

1. II (prothrombin) 2. X 3. IX 4. XI 5. XII

Question 33

What is the most important protease inhibitor that inactivates the clotting factors?

Answer 33

Antithrombin III

Question 34

Antithrombin III is activated by what?

Answer 34

Heparin

Question 35

Thrombomodulin is found on the surface of endothelial cells, it binds to what?

Answer 35

Circulating thrombin

Question 36

What does protein C degrade?

Answer 36

1. Factor V a | 2. Factor VIII a

Question 37

Thrombomodulin is present only on what?

Answer 37

intact endothelium

Question 38

Plasmin degrades what?

Answer 38

The fibrin clot

Question 39

Active plasmin is formed only where?

Answer 39

in the fibrin clot where it is needed

Question 40

The fibrin complex can be activated by what?

Answer 40

Tissue type plasminogen activator (tPA)

Question 41

tPA (tissue type plasminogen activator) is what type of protease?

Answer 41

Serine

Question 42

Plasminogen can also be activated by what?

Answer 42

1. Urokinase | 2. Streptokinase

Question 43

tPA can be used in the event of what?

Answer 43

Acute MI (if administered within an hour, very risky)

Question 44

Clotting can be inhibited by removing what?

Answer 44

Calcium ions

Question 45

Which factors of the clotting cascade depend on calcium?

Answer 45

All gamma-carboxyglutamate containing factors

Question 46

Which factors contain gamma-carboxyglutamate?

Answer 46

1. prothrombin 2. VII 3. IX 4. X

Question 47

Bleeding time is prolonged in what?

Answer 47

Platelet deficiencies

Question 48

Activated partial thromboplastin time (PTT) is used to measure what?

Answer 48

Efficacy of Heparin

Question 49

PTT tests which pathways?

Answer 49

1. Intrinsic Pathway | 2. final common pathway

Question 50

Prothrombin time is prolonged in deficiencies of which pathways?

Answer 50

1. Extrinsic pathway | 2. Final common pathway

Question 51

PT is used routinely to measure what therapy?

Answer 51

Coumadin

Question 52

Hemophilia A is the result of a deficiency in what?

Answer 52

Factor VIII

Question 53

Hemophilia B is a result of a deficiency in what?

Answer 53

Factor IX

Question 54

Hemophilia has what inheritance pattern?

Answer 54

X-linked (Almost exclusively found in males)

Question 55

What is the only effective therapy for hemophilia?

Answer 55

Injections of Factor VIII