Blood Coagulation & Wound Repair (Exam III) Flashcards

1
Q

When does the blood coagulation process occur

A

When there is injury to a blood vessel

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2
Q

What are the four steps to the coagulation process

A

1- blood vessels around wound constrict
2- activated platelets stick to injury site
3- platelets aggregate together to form plug
4- platelets and damaged tissue release clotting factors
5- mesh of fibrin (clot) is formed

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3
Q

Vasoconstriction and platelet response is part of what stage of hemostasis

A

Primary hemostasis

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4
Q

In primary hemostasis platelet aggregation at the site of injury is mediated by:

A

Platelet receptors, platelet-derived agonist, platelet-derived adhesion proteins, and plasma-derived adhesion proteins

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5
Q

What stage of hemostasis does the clotting cascade occur in?

A

Secondary hemostasis

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6
Q

The clotting cascade consists of a cascade of coagulation of:

A

Serine proteases

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7
Q

The coagulation of serine proteases culminates the cleavage of:

A

Soluble fibrinogen by thrombin

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8
Q

What does thrombin cleave

A

Soluble fibrinogen

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9
Q

Once the thrombin cleaves the soluble fibrinogen, the fibrinogen is converted into:

A

Insoluble fibrin

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10
Q

The insoluble fibrin formed for the cleavage of fibrinogen (by thrombin) forms _____ at the site of injury

A

Cross-linked fibrin mesh

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11
Q

Occurs simultaneously to platelet aggregation

A

Fibrin generation

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12
Q

Clotting cascade:

1- damage to the blood vessel results in release of ______
2- the clotting factors catalyze the conversion of _____ to _____
3- Thrombin cleaves _____ to _____
4- the fibrin strand adhere to the plug to form a ___

A
  1. Clotting factors
  2. Prothrombin to thrombin
    3- soluble fibrinogen to insoluble fibrin
    4- clot
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13
Q

Platelet activation and its response

A

Primary hemostasis

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14
Q

When you have an exposed underlying epithelium or ECM this will cause the platelets to stick to:

A

Collagen

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15
Q

The intial binding of the platelets to the exposed collagen involves them to undergo a release reaction to release:

A

Von Willebrand factor

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16
Q

When Von Willebrand factor is released from the exposed collagen, what will bind to it

A

GP1B

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17
Q

The binding of Von Willebrand factor to GP1B is very:

A

Weak

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18
Q

As a result of the weak binding of Von Willebrand and GP1B the platelets that do stick will undergo a release reaction to secrete (3)

A

ADP
Thrombaxe A2
Serotonin

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19
Q

Serotonin and Thromboxane A2 stimulate

A

Vasoconstriction

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20
Q

When Seratonin and Thromboxane stimulate vasoconstriction this results in:

A

Reduced blood flow to wound

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21
Q

ADP and thromboxane A2 cause other platelets to:

(3)

A

Become sticky, attach and undergo platelet release reaction

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22
Q

The platelet release reaction continues until:

A

Platelet plug is formed

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23
Q

A-nuclear sacs of vessels and molecules with dense granules, that contain ADP, ATP, Serotonin, calcium, epinephrine, histamine, other coagulation factors, growth factors, and adhesion molecules

A

Platelets

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24
Q

Serotonin is synthesized from what amino acid

A

Tryptophan

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25
Q

What cells produce serotonin (in the gut)

A

Entrochromaffin

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26
Q

Thromboxane A2 is initially synthesized from

A

Arachidonic acid

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27
Q

How does arachidonic acid form thromboxane A2?

A

Arachidonic acid —> cyclo-oxygenase enzyme —> endoperoxidase —> thromboxane synthetase enzyme —> thromboxane A2

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28
Q

Thromboxane A2’s action is antagonized by

A

Prostacyclins

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29
Q

What two molecules are formed from arachidonic acid?

A

Thromboxane A2
Prostacyclins

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30
Q

Platelets are a store house of

A

Thromboxane A2

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31
Q

What cells produce the prostacyclins

A

Endothelial cells

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32
Q

Prostacyclins and thromboxane A2 will oppose eachother in terms of

A

Contraction and relaxation

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33
Q

GPIB, GPIA, GPIIb-IIIa are all

A

Glycoproteins

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34
Q

The initial activating event when platelets bind Von Willebrand factor is mediated by:

A

GP1B

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35
Q

Firm adhesion of platelets to the subendothelia is mediated by

A

GPIIb-IIIa

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36
Q

What activates platelets

A

GPVI

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37
Q

When the platelet is resting describe the state of GPIIb-IIIa complex

A

Not active - can only weakly bind

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38
Q

When the platelet is activated describe the state of GPIIb-IIIa complex

A

Activate - can now strongly bind

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39
Q

When the platelets is activated why can GPIIb-IIIa complex bind so firmly

A

Because GPIIb-IIIa undergoes a confirmational change and exposes new binding sites for VWF or fibrinogen

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40
Q

The activate GPIIb-IIIa that binds strongly to VWF promotes strong adhesion to the vessel wall

What part of aggregation is this?

A

Primary aggregation

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41
Q

Platelet aggregation is dependent upon ___ which allows a quicker activation and sustained response

A

ADP

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42
Q

How many pathways does the clotting cascade involve

A

3

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43
Q

What pathway in the clotting cascade is activated by external trauma that causes blood to escape the vascular system

A

Extrinsic

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44
Q

What clotting cascade pathway functions quickly

A

Extrinsic

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45
Q

What clotting factors does the extrinsic pathway involve

A

Clotting factor VII

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46
Q

What clotting cascade pathway is activated by trauma inside the vascular system (activated by platelets, exposed endothelium, chemicals or collagen)

A

Intrinsic

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47
Q

What clotting cascade pathway has a slow response

A

Intrinsic

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48
Q

What clotting factors does the intrinsic pathway use?

A

XII, XI, IX, VIII

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49
Q

The intrinsic and extrinsic pathways both converge and finish the clot production in the

A

Common pathway

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50
Q

What clotting factors are involved in the common pathway

A

I, II, V, X

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51
Q

Activated partial thromboplastin time measures

A

Intrinsic pathway

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52
Q

Prothrombin time measures

A

The extrinsic pathway

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53
Q

In the coagulation cascade most of our factors exist in a ____ form and has to be converted into a ____ form

A

Inactive
Active

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54
Q

Common name for factor-I

A

Fibrinogen

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55
Q

What cleaves fibrinogen into fibrin

A

Thrombin

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56
Q

Common name for factor-II

A

Prothrombin

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57
Q

Prothrombin is activated on the surface of activated platelets by

A

Prothrombinase complex

58
Q

What is an important modification that takes place in many factors of the coagulation process

A

Formation of carboxyglutamate residue

59
Q

Thrombin, factor VII, IX, X all contain a:

A

Unique modified glutamate residue

60
Q

Uniquely modified glutamate residues on thrombin, factor VII, IX, and X will:

A

Anchor them on cell surface in stable form

61
Q

The uniquely modified glutamate residue on thrombin, factor VII, IX, X (carboxyglutamate) will undergo a reaction that is dependent upon

A

Vitamin K

62
Q

Vitamin K is important in the:

A

Clotting cascade

63
Q

What are the fat soluble vitamins

A

A, D, E, K

64
Q

What is the name of the inactive form of the factor that undergoes a vitamin K-dependent carboxylation reaction

A

Prozymogen

65
Q

What is the prozymogen in the vitamin-K carboxyglutamate reaction

A

Glutamate residue

66
Q

In the vitamin-K carboxyglutamate reaction:

The glutamate residue (the prozymogen) in the presence of vitamin K and molecular oxygen leads to the addition of a ______ on the side chain of the glutamate

A

Gamma-carboxyglutamate residue

67
Q

When a glutamate residue undergoes a vitamin K-dependent carboxylase it forms a ______ and _____

A

Vitamin K epoxide
Carboxylated prozymogen

68
Q

In the carboxyglutamate reaction, the vitamin K epoxide gets converted back into

A

Vitamin K hydroquinone

69
Q

In a carboxyglutamate reaction:

The vitamin K epoxide gets converted back into the vitamin K hydroquinone via what two enzymes

A

Vitamin K epoxide reductase
Vitamin K reductase

70
Q

In a carboxyglutamate reaction:

Why must some of the vitamin K epoxide return back to the hydroquinone form?

A

To keep adequate levels of the vitamin K hydroquinone form available for carboxyglutamate carboxylations

71
Q

What are the extrinsic factors dependent on vitamin K
What are the intrinsic factors dependent on vitamin K
What are the common pathway factors dependent on vitamin K

A

Extrinsic: factor-VII
Intrinsic: factor-IX
Common: factor-II, factor-X

72
Q

If vitamin K levels are not adequate, factors- II, VII, IX, X cannot properly form:

A

the fibrin clot

73
Q

What is the initial strength of platelets in the platelet plug

A

Weak

74
Q

What has to happen in order to solidify the platelet plug to prevent further bleeding

A

Fibrin mesh

75
Q

Due to the cleavage of fibrinogen by thrombin the fibrinogen initially forms

A

Fibrin monomers

76
Q

The fibrin monomers created by thrombin acting on fibrinogen ultimately aggregate and cross link by an enzyme called:

A

Transglutaminase (factor-XIII)

77
Q

Name the domains on the fibrin molecules:

A

Two D domains
One E domain (in middle)

78
Q

What subunits make up the D domain of the fibrin molecule

A

Gamma and beta subdomains

79
Q

The cross linking of the fibrin domains by transglutaminase forms ____ between the domains

A

Peptide bonds

80
Q

The cross linking of the domains of fibrin forms a:

A

Mesh

81
Q

Peptide bonds between the domains in fibrin are created by:

A

Transglutaminase

82
Q

We start with two fibrin molecules and then transglutaminase takes a side chain ____ on one monomer and then a side chain ______ on the other monomer and cross links them to form a peptide bond

A

Lysine residue
Glutamine residue

83
Q

What molecule breaks down the fibrin mesh

A

Plasmin

84
Q

Plasmin is derived from

A

Plasminogen

85
Q

Further processing of plasmin gives rise to

A

Crinkle proteins

86
Q

Crinkle proteins are part of the

A

Angiostatin molecule system

87
Q

Plasmin main role in blood coagulation system is to break down:

A

Fibrin monomers into fragments

88
Q

The conversion of plasmin from plasminogen involves what factors:

A

TPA
Urokinase
Factor 11a
Factor 12a
Kalikrein

89
Q

In of the conversion of plasminogen to plasmin include

A

Alpha-2 antiplasmin
Alpha-2 macroglobulin

90
Q

Wound healing is a ____ process in which skin or other tissues repairs itself after injury

A

Complex

91
Q

The classical model of wound healing can be divided into four sequential overlapping phases that include:

A

1- hemostasis
2- inflammatory
3- proliferative
4- remodeling

92
Q

Within minutes post-injury, platelets aggregate at the injury site to form a fibrin clot which acts to control bleeding- what is this process called?

A

Hemostasis

93
Q

Bacteria and debris are phagocytosed and removed from the wound site, factors are released that caused migration and division of cells involved in the proliferative phase - what phase of wound healing is this?

A

Inflammatory phase

94
Q

Angiogenesis, collagen deposition, granulation tissue formation, epithelialization, and wound contraction occur in what phase of wound healing

A

Proliferative phase

95
Q

Collagen is remodeled and realigned along tension force lines and cells no longer needed are removed by apoptosis in what phase of wound healing

A

Remodeling phase

96
Q

Platelets are involved in what stage of wound healing

A

Hemostasis

97
Q

Neutrophils, monocytes, macrophages and growth factors are involved in what stage of wound healing

A

Inflammation

98
Q

Keratinocytes, fibroblasts and endothelial cells are involved in what stage of wound healing

A

Proliferation and remodeling

99
Q

Serves as a regulator of platelet function and a mediator of hemostasis

A

Fibronectin

100
Q

Fibronectin exists in what two forms

A

Plasma form and cellular form

101
Q

The plasma form of fibronectin is secreted by _____ and modulates ____

A

Hepatocytes; platelet function

102
Q

The cellular form of fibrinogen is secreted by cells as part of the _____ and functions as a ____

A

ECM; scaffold protein

103
Q

What are two types of anticoagulants present in tube when you get blood drawn

A

Acid-citrate-dextrose solution
EDTA

104
Q

How do acid-citrate-dextrose solution and EDTA function?

A

Bind calcium to prevent clotting

105
Q

A test used to help detect and diagnose a bleeding disorder or excessive clotting disorder

A

Prothrombin time (PT)

106
Q

INR stands for

A

International normalized ratio

107
Q

Calculated from PT result and used to monitor how well blood thinning medication (especially Coumadin/Warfarin) is working to prevent blood coagulation

A

INR

108
Q

Developed to standardize the results of prothrombin time universally

A

INR

109
Q

A measure of the integrity of the extrinsic and final common pathways of the coagulation cascade- consists of tissue factor and factor VII, II (prothrombin), V, X and fibrinogen

A

Prothrombin time

110
Q

The prothrombin time is measured in ____ and compared to a ____

A

Seconds; normal range

111
Q

Normal range of INR

A

Below 1.1

112
Q

INR of effective therapeutic range or mechanical heart valve

A

2.0-3.0

113
Q

When the INR is higher than the recommended range it means

A

Blood clots slowly

114
Q

When INR is lower than the recommended range it means

A

Blood clots quicker than desired

115
Q

Diseased states that can interfere with wound healing include:

A

Diabetes
Venous/arterial disease
Old age
Infection

116
Q

List medication that are used to reduce/prevent blood coagulation (blood thinners)

(5)

A
  1. Warfarin
  2. Pradaxa
  3. Xarelto
  4. Eliquis
  5. Plavix
117
Q

Blood thinners are most commonly used in patients with previous

A

DVT

118
Q

Warfarin competitively inhibits:

A

Vitamin K Epoxide Reductase Complex 1 (VKORC1)

119
Q

Warfarin function by not allowing the epoxide to return back to:

A

Hydroquinone form

120
Q

Warfarin can complete functional:

A

Vitamin K reserve

121
Q

Warfarin can be neutralized by

A

High dose Vitamin K

122
Q

Xarelto and Eliquis target:

A

Factors-Xa

123
Q

Eliquis and Xarelto are competitive inhibitors of what factor

A

Factor-Xa

124
Q

Factor-Xa is necessary for conversion of:

A

Prothrombin into thrombin

125
Q

What drug directly inhibits thrombin

A

Pradaxa

126
Q

X-linked recessive disorder that results in decreased factor-VIII

A

Hemophilia A

127
Q

Hemophilia A can be treated with:

A

Recombinant factor-VIII

128
Q

Known as Christmas disease, X-linked recessive disorder resulting in decreased factor-IX

A

Hemophilia B

129
Q

Hemophilia B can be treated with

A

Recombinant factor IX

130
Q

Who is prominent family that had hemophilia B

A

Queen Victoria

131
Q

Enzyme that cleaves protein substrates into different parts

A

Protease

132
Q

Trypsin prefers to cleave at what residues

A

Arginine and lysine

133
Q

Trypsin is what type of protease

A

Serine

134
Q

Activation of a zymogen commonly occurs by

A

Proteolytic cleavage

135
Q

Protein kinases usually add phosphate to what amino acids in the side chains of proteins

A

Serine , threonine and tyrosine

136
Q

Chemical compound that that sequesters calcium ions and draw it away for coagulation proteins

A

EDTA

137
Q

Represent calcium binding sites on coagulation and bone proteins

A

GLA residues

138
Q

Liquid phase of clothed blood after spinning out clot

A

Serum

139
Q

Liquid phase of unclottted blood still containing clotting proteins (cells have centrifuged away)

A

Plasma

140
Q

Inhibitor of cyclooxygenase which catalyzes formation of prostaglandin E2 and other prostaglandins and leukotrienes

A

Aspirin (NSAID)

141
Q

Site of metabolism of fat soluble vitamin K

A

Gut bacteria