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Flashcards in Coag Deck (108):
1

What is hemostasis?

The cessation of bleeding from a cut or severed vessel

2

What are the five hemostasis systems?

Vascular
platelet
Coagulation
Anticoagulation
Fibrinolytic

3

Deficiencies in any of the clotting systems can lead to what?

Hemorrhaging
Thrombosis

4

What is vasoconstriction controlled by?

Local factors by the tissues

5

What is the first response to a cut?

Local factors released to vasoconstrict
Platelets

6

Activated platelets at the side of injury release what? What do these do?

Thromboxane (A2)
Serotonin

Stimulate vasoconstriction

7

What does the coagulation system produce that induces blood vessel endothelial cells to produce endothelin 1?

Thrombin

8

What is the function of endothelin 1?

Potent vasoconstrictor

9

Platelets adhere to the side of a vessel through what? What does this cause?

Surface glycoproteins receptors

Causes change in shape of platelets, and activates further platelets

10

What is in the ECM that is exposed during an injury, and causes initial platelet binding? What is the receptor on the platelet?

von Willebrand factor (vWf)

Receptor = GP1-b-alpha

11

What is Willebrand factor disease?

loss of vWf, leading to increased bleeding

12

After initial platelet tethering, what protein binds collagen in the ECM, that begins to activate platlets?

Platelet glycoprotein VI

13

What is the role of fibrinogen?

A moleculer glue between activated GPIIa/IIIb

14

What are the three granules that platelets release?

1. Dense granules
2. Alpha granules
3. chemokines

15

What is the function of GPIb-alpha on platelets?

Initial tethering of platelet

16

What is the function of GPVI on platelets? What does it bind to?

Binds collagen to initially activate platelet and release ADP, 5HT, and TXA2

17

What is the fuction of GPIIb/IIa on platelets?

Facilitates platelet-platelet interactions whn joined with fibrinogen

18

What is the active drug in plavex?

Clopidogrel (P2Y12)

19

Why is it important that clotting be reversible?

So that clots can be destroyed in places not needed

20

What is thrombosis?

Inappropriate clot formation

21

True or false: the coagulation and anticoagulation systems act in isolation of each other

False

22

How does vasoconstriction aid in the process of a clot formation?

Allows blood to flow more slowly, and allow platelets to have a better chance of adhering to an injury site

23

How do platelets adhere to the site of vessel injury?

Through cell surface glycoproteins activation, forming finger-like extensions

24

How do platelets recruit more of themselves to the site of injury?

Release factors (ADP and Ca)

25

What is the function of the initial platelet response? How strong is this?

Form a platelet plug--not very strong initially

26

Where is von Willebrand factor found? What does it do?

Found in the plasma and ECM, until it encounters exposed collage in the ECM. It binds to this, and recruits platelets

27

What happens to the platelet after it binds to vWF?

The GPVI binds to collagen in the ECM injury site

28

What does the platelet produce to recruit more of itself?

ADP, serotonin, and thromboxane A2

29

What is the function of the factors that platelets produce (ADP, serotonin, and thromboxane A2) when bound to the ECM?

bind to G-protein coupled receptors on platelets already adhering to the injury site, to further activate them

30

What is the function of GPVI on platelets?

Binds to the collagen in the ECM

31

What is the protein that is on platelets that, when activated, allows for binding of fibrinogen?

GPIII/IIb

32

What is the function of the GPII/IIb protein found on platelets?

Binds fibrinogen

33

What is fibrinogen? Where is it produced and found?

Molecular glue for platelets

Produced by liver
Found in circulation in high amounts

34

What is the function of GpIIb/IIIa inhibitors in treating MIs?

Inhibit platelet aggregation that occurs

35

What is the function of the purinergic P2Y12 receptors on platelets? What is it activated by?

Activated by ADP, and facilitates the aggregation of platelets

36

What is the MOA of Plavex?

Antagonist to P2Y12

37

What are the three G-coupled protein receptors on platelets?

Purinergic P2Y12
Protease activated receptors
Thromboxane A2 receptors

38

What are the two chemicals released by endothelial cells to inhibit platelet aggregation?

NO
PGI2 (prostacycline)

39

What do NO and PGI2 do after release from endothelial cells?

Vasodilate
Prevent platelet adhesion

40

What is the charge on platelets? Endothelial cells? Why is this significant?

Both negative, meaning they repel each other when there is no damage

41

What is the end result of the platelet system?

Loose platelet clot

42

What is the function of the coagulation system? How does this compare to the platelet system?

Form insoluble fibrin clots that are much more secure than platelet plugs

43

What is the protein from the coag system that cross links and forms a meshwork to trap blood and serum in a clot?

Fibrin

44

What is the precursor form of fibrin? How is it turned into fibrin?

Fibrinogen, cleaved by a protease-Thrombin

45

What is the function of thrombin? (2)

Cleaves fibrinogen to form fibrin monomers
Activates Factor XIII

46

What activates factor XIII? What does it do?

Induces fibrin fibers to cross-link, forming a stable blood clot

47

What is the precursor form of thrombin? How does it become activated?

Prothrombin
Formed by a complex cascade of coag factors

48

What are the descriptive names for factors I, II, III, and IV?

I = Fibrinogen
II = Prothrombin
III = Tissue factors
IV = Ca

49

Where is prothrombin found? What produces it?

Plasma
Liver

50

What are the two pathways that activate Prothrombin?

Extrinsic pathway
Intrinsic pathway

51

What starts the extrinsic pathway?

Tissue damage

52

What happens in the extrinsic pathway after the initial tissue damage (and factor III release)?

Factor VII activated

53

What does factor VII do in the extrinsic pathway?

Activates factor X

54

What does factor X do in the extrinsic pathway?

Activates factor 5, then thrombin

55

What is the composition of tissue factor complex in the extrinsic pathway?

Factor VIIa
Ca

Activates factor X

56

How can thrombin increase the rate of the extrinsic pathway activation?

Increases factor V

57

What are the four components of the prothrombin activator complex? What does it do?

Factors X and V, Ca, and phospholipids

Increases thrombin activation

58

How does the small amount of thrombin that is induced from the extrinsic pathway lead to an autocrine-like action to increase its activity?

Form the prothrombin activator complex

59

How is the intrinsic pathway begun? What is the first factor to be activated?

Exposure of collagen leads to the activation of factor 12

60

What is the order of activation of the factors in the intrinsic pathway?

12, 11, 9, 10

61

What happens after factor 9 activation in the intrinsic coag pathway? How fast is this?

Factor 10 is activated slowly

62

What does factor 10 activated in the extrinsic and intrinsic pathway?

Activates prothrombin into thrombin

63

What are the components of the tenase complex in the intrinsic pathway?

factors 9 and 8
Ca
Phospholipids

64

Hemophilia A is caused by a deficiency in what factor? What does this inhibit the assembly of?

VIII (8)

Thus there is no tenase complex

65

Where do the extrinsic and intrinsic pathway converge?

at factor X

66

Which factors require vitamin K for the activity?

2, 7, 9, and 10 (vit K was born in 1972, iff 1=10) also, S and C proteins

67

What is the purpose of vit K in the production of coag factors?

Used as a cofactor in the carboxylation of key glutamate residues in the factors (allows Ca to bind)

68

What is the MOA of Warfarin?

Blocks the reduction of Vit K after Vit K has been oxidized in the production of coag factors

69

Why are newborns and liver pts given Vit K?

Vit K comes from gut flora and is fat soluble. If there is no flora (babes) or if there is no bile to take up fatty soluble vit K, then vit K deficiency results

70

What does the activated partial thromboplastin time (aPTT or PTT) measure?

The speed of the intrinsic pathway

71

How is the PTT done?

Pt's anticoagulated plasma is placed in tube and mixed with phospholipids and a negatively charged bead. Ca is added later to initiate clotting

72

What does the prothrombin time (PT) measure?

The speed of the intrinsic pathway

73

How is the prothrombin time measurement performed?

Pt's blood is collected into citrated anticoagulant. Then Ca is added in the presence of thromboplastin and time is measured

74

What is the function of thrombomodulin?

Interacts with thrombin to inactivate it, by converting thromin into an anticoagulant enzyme

75

Where is thrombomodulin found?

On endothelial cells

76

What is the function of protein C? What activates it?

Activated by thrombomodulin/thrombin complex that degrades Factors Va and VIIIa

77

What is factor V leiden thrombophilia?

Mutation in factor V prevents it from being inactivated by protein C complex

(=hypercoagulability)

78

What would be the consequence of a deficiency in protein C?

hypercoagulability

79

What would a deficiency in thrombomodulin cause?

Hypercoagulability

80

What is the tissue factor that is secreted by endothelial cells, that reduces thrombin formation by inhibiting factor VIIa/tissue factor complex?

Tissue factor pathway inhibitor (TFPI)

81

What is antithrombin (type of molecule, what produces it, where its found), and how does it work?

It is a circulating protease produced by the liver, that inhibits thrombin production, and destroys thrombin

82

What does antithrombin need in order to become activated?

Heparin sulfate

83

True or false: heparin and antithrombin both have anticoagulation effects alone, but work faster when bound together

False- antithrombin is slow, but works

Heparin has no intrinsic anticoagulation effect

84

Where is heparin sulfate usually found?

Endothelial cells surface in low quantities

85

What is the function of the fibrinolytic system? When and where does it work?

Degradation of fibrin clots (after an injury has healed or in inappropriate places)

86

What is the main protease that cleaves fibrin is what?

Plasmin

87

What is the inactivated state of plasmin? Where is it found, and what organ produces it?

Plasminogen, which is produced by the liver and is found circulating in the blood or in a clot

88

What activates plasminogen to plasmin? Where is this substance produced?

tPA (tissue Plasminogen Activator)

Produced by vascular endothelial cells

89

What are the two factors that inhibit tPA? Where are each of these found?

Plasminogen activator inhibitor (PAI)- endothelial cells
Alpha-2-plasmin inhibitor - circulation

90

What happens to plasminogen when a clot form via platelets and fibrin? What happens when the clot produces tPA?

Become enmeshed in the clot.

When the clot slowly increases tPA production, allows plasminogen to become activated, and breaks up the clot

91

Deficiency in which factor produces hemophilia A and which for B? What is the inheritance pattern of this?

8A
9B

This is an X-linked recessive trait

92

Which are the factors involved in the extrinsic pathway (in order)?

3
7
10
5

93

What are the factors that are in the intrinsic pathway (in order)?

12
11
9
8
10
5

94

Which clotting factor(s) is/are at the end of both the intrinsic and extrinsic pathway? What does this/ do these do?

factor 10 and 5

These combine to form the prothrombin activator

95

What are the two factors that make up the prothrombin activator complex?

10 and 5

96

Which clotting factor(s) is/are inhibited by thrombomodulin?

factor 5 and 8

97

Describe the pathway that thrombomodulin takes to inhibit factor 5. (3ish steps)

Thrombomodulin bind thrombin
activation of protein C, then S

Inhibition

98

Where is antithrombin found? Where is heparin found? What is the effect of them binding?

Antithrombin is circulating in the tissue
Heparin is on endothelial cell

Binding increases antithrombin activity

99

What is the condition where there is not enough platelets to form a clot? What are the symptoms of severe cases of this?

Thrombocytopenia

Small purpurea d/t many tiny hemorrhages

100

What is the effect of liver disease on clotting factors? How is this effected?

Reduces platelets and clotting factors through a lack of vit K uptake

101

What is the enzyme that reduces Vit K back to its usable form?

VKOR

102

What is the MOA of asprin's anticoagulant ability?

Inhibits TXA2

103

What are the pro-aggregation factors for platelets?

1. TXA2
2. Lower Blood flow

104

What are the anti-aggregation factors for platelets?

1. PGI2 and NO
2. Higher blood flow

105

What is bernard-Soulier syndrome?

A deficiency of GpIb, resulting in a lack of coagulation

106

What is the drug that blocks GpIIb/IIIa?

abciximab

107

What is Glanzmann thrombasthenia?

A deficiency of GpIIb/IIIa

108

Which two factors comprise the Tenase factor?

8 and 9