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
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
3
Q
Vasoconstriction and platelet response is part of what stage of hemostasis
A
Primary hemostasis
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
5
Q
What stage of hemostasis does the clotting cascade occur in?
A
Secondary hemostasis
6
Q
The clotting cascade consists of a cascade of coagulation of:
A
Serine proteases
7
Q
The coagulation of serine proteases culminates the cleavage of:
A
Soluble fibrinogen by thrombin
8
Q
What does thrombin cleave
A
Soluble fibrinogen
9
Q
Once the thrombin cleaves the soluble fibrinogen, the fibrinogen is converted into:
A
Insoluble fibrin
10
Q
The insoluble fibrin formed for the cleavage of fibrinogen (by thrombin) forms _____ at the site of injury
A
Cross-linked fibrin mesh
11
Q
Occurs simultaneously to platelet aggregation
A
Fibrin generation
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
- Clotting factors
- Prothrombin to thrombin
3- soluble fibrinogen to insoluble fibrin
4- clot
13
Q
Platelet activation and its response
A
Primary hemostasis
14
Q
When you have an exposed underlying epithelium or ECM this will cause the platelets to stick to:
A
Collagen
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
16
Q
When Von Willebrand factor is released from the exposed collagen, what will bind to it
A
GP1B
17
Q
The binding of Von Willebrand factor to GP1B is very:
A
Weak
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
19
Q
Serotonin and Thromboxane A2 stimulate
A
Vasoconstriction
20
Q
When Seratonin and Thromboxane stimulate vasoconstriction this results in:
A
Reduced blood flow to wound
21
Q
ADP and thromboxane A2 cause other platelets to:
(3)
A
Become sticky, attach and undergo platelet release reaction
22
Q
The platelet release reaction continues until:
A
Platelet plug is formed
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
24
Q
Serotonin is synthesized from what amino acid
A
Tryptophan
25
What cells produce serotonin (in the gut)
Entrochromaffin
26
Thromboxane A2 is initially synthesized from
Arachidonic acid
27
How does arachidonic acid form thromboxane A2?
Arachidonic acid —> cyclo-oxygenase enzyme —> endoperoxidase —> thromboxane synthetase enzyme —> thromboxane A2
28
Thromboxane A2’s action is antagonized by
Prostacyclins
29
What two molecules are formed from arachidonic acid?
Thromboxane A2
Prostacyclins
30
Platelets are a store house of
Thromboxane A2
31
What cells produce the prostacyclins
Endothelial cells
32
Prostacyclins and thromboxane A2 will oppose eachother in terms of
Contraction and relaxation
33
GPIB, GPIA, GPIIb-IIIa are all
Glycoproteins
34
The initial activating event when platelets bind Von Willebrand factor is mediated by:
GP1B
35
Firm adhesion of platelets to the subendothelia is mediated by
GPIIb-IIIa
36
What activates platelets
GPVI
37
When the platelet is resting describe the state of GPIIb-IIIa complex
Not active - can only weakly bind
38
When the platelet is activated describe the state of GPIIb-IIIa complex
Activate - can now strongly bind
39
When the platelets is activated why can GPIIb-IIIa complex bind so firmly
Because GPIIb-IIIa undergoes a confirmational change and exposes new binding sites for VWF or fibrinogen
40
The activate GPIIb-IIIa that binds strongly to VWF promotes strong adhesion to the vessel wall
What part of aggregation is this?
Primary aggregation
41
Platelet aggregation is dependent upon ___ which allows a quicker activation and sustained response
ADP
42
How many pathways does the clotting cascade involve
3
43
What pathway in the clotting cascade is activated by external trauma that causes blood to escape the vascular system
Extrinsic
44
What clotting cascade pathway functions quickly
Extrinsic
45
What clotting factors does the extrinsic pathway involve
Clotting factor VII
46
What clotting cascade pathway is activated by trauma inside the vascular system (activated by platelets, exposed endothelium, chemicals or collagen)
Intrinsic
47
What clotting cascade pathway has a slow response
Intrinsic
48
What clotting factors does the intrinsic pathway use?
XII, XI, IX, VIII
49
The intrinsic and extrinsic pathways both converge and finish the clot production in the
Common pathway
50
What clotting factors are involved in the common pathway
I, II, V, X
51
Activated partial thromboplastin time measures
Intrinsic pathway
52
Prothrombin time measures
The extrinsic pathway
53
In the coagulation cascade most of our factors exist in a ____ form and has to be converted into a ____ form
Inactive
Active
54
Common name for factor-I
Fibrinogen
55
What cleaves fibrinogen into fibrin
Thrombin
56
Common name for factor-II
Prothrombin
57
Prothrombin is activated on the surface of activated platelets by
Prothrombinase complex
58
What is an important modification that takes place in many factors of the coagulation process
Formation of carboxyglutamate residue
59
Thrombin, factor VII, IX, X all contain a:
Unique modified glutamate residue
60
Uniquely modified glutamate residues on thrombin, factor VII, IX, and X will:
Anchor them on cell surface in stable form
61
The uniquely modified glutamate residue on thrombin, factor VII, IX, X (carboxyglutamate) will undergo a reaction that is dependent upon
Vitamin K
62
Vitamin K is important in the:
Clotting cascade
63
What are the fat soluble vitamins
A, D, E, K
64
What is the name of the inactive form of the factor that undergoes a vitamin K-dependent carboxylation reaction
Prozymogen
65
What is the prozymogen in the vitamin-K carboxyglutamate reaction
Glutamate residue
66
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
Gamma-carboxyglutamate residue
67
When a glutamate residue undergoes a vitamin K-dependent carboxylase it forms a ______ and _____
Vitamin K epoxide
Carboxylated prozymogen
68
In the carboxyglutamate reaction, the vitamin K epoxide gets converted back into
Vitamin K hydroquinone
69
In a carboxyglutamate reaction:
The vitamin K epoxide gets converted back into the vitamin K hydroquinone via what two enzymes
Vitamin K epoxide reductase
Vitamin K reductase
70
In a carboxyglutamate reaction:
Why must some of the vitamin K epoxide return back to the hydroquinone form?
To keep adequate levels of the vitamin K hydroquinone form available for carboxyglutamate carboxylations
71
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
Extrinsic: factor-VII
Intrinsic: factor-IX
Common: factor-II, factor-X
72
If vitamin K levels are not adequate, factors- II, VII, IX, X cannot properly form:
the fibrin clot
73
What is the initial strength of platelets in the platelet plug
Weak
74
What has to happen in order to solidify the platelet plug to prevent further bleeding
Fibrin mesh
75
Due to the cleavage of fibrinogen by thrombin the fibrinogen initially forms
Fibrin monomers
76
The fibrin monomers created by thrombin acting on fibrinogen ultimately aggregate and cross link by an enzyme called:
Transglutaminase (factor-XIII)
77
Name the domains on the fibrin molecules:
Two D domains
One E domain (in middle)
78
What subunits make up the D domain of the fibrin molecule
Gamma and beta subdomains
79
The cross linking of the fibrin domains by transglutaminase forms ____ between the domains
Peptide bonds
80
The cross linking of the domains of fibrin forms a:
Mesh
81
Peptide bonds between the domains in fibrin are created by:
Transglutaminase
82
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
Lysine residue
Glutamine residue
83
What molecule breaks down the fibrin mesh
Plasmin
84
Plasmin is derived from
Plasminogen
85
Further processing of plasmin gives rise to
Crinkle proteins
86
Crinkle proteins are part of the
Angiostatin molecule system
87
Plasmin main role in blood coagulation system is to break down:
Fibrin monomers into fragments
88
The conversion of plasmin from plasminogen involves what factors:
TPA
Urokinase
Factor 11a
Factor 12a
Kalikrein
89
In of the conversion of plasminogen to plasmin include
Alpha-2 antiplasmin
Alpha-2 macroglobulin
90
Wound healing is a ____ process in which skin or other tissues repairs itself after injury
Complex
91
The classical model of wound healing can be divided into four sequential overlapping phases that include:
1- hemostasis
2- inflammatory
3- proliferative
4- remodeling
92
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?
Hemostasis
93
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?
Inflammatory phase
94
Angiogenesis, collagen deposition, granulation tissue formation, epithelialization, and wound contraction occur in what phase of wound healing
Proliferative phase
95
Collagen is remodeled and realigned along tension force lines and cells no longer needed are removed by apoptosis in what phase of wound healing
Remodeling phase
96
Platelets are involved in what stage of wound healing
Hemostasis
97
Neutrophils, monocytes, macrophages and growth factors are involved in what stage of wound healing
Inflammation
98
Keratinocytes, fibroblasts and endothelial cells are involved in what stage of wound healing
Proliferation and remodeling
99
Serves as a regulator of platelet function and a mediator of hemostasis
Fibronectin
100
Fibronectin exists in what two forms
Plasma form and cellular form
101
The plasma form of fibronectin is secreted by _____ and modulates ____
Hepatocytes; platelet function
102
The cellular form of fibrinogen is secreted by cells as part of the _____ and functions as a ____
ECM; scaffold protein
103
What are two types of anticoagulants present in tube when you get blood drawn
Acid-citrate-dextrose solution
EDTA
104
How do acid-citrate-dextrose solution and EDTA function?
Bind calcium to prevent clotting
105
A test used to help detect and diagnose a bleeding disorder or excessive clotting disorder
Prothrombin time (PT)
106
INR stands for
International normalized ratio
107
Calculated from PT result and used to monitor how well blood thinning medication (especially Coumadin/Warfarin) is working to prevent blood coagulation
INR
108
Developed to standardize the results of prothrombin time universally
INR
109
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
Prothrombin time
110
The prothrombin time is measured in ____ and compared to a ____
Seconds; normal range
111
Normal range of INR
Below 1.1
112
INR of effective therapeutic range or mechanical heart valve
2.0-3.0
113
When the INR is higher than the recommended range it means
Blood clots slowly
114
When INR is lower than the recommended range it means
Blood clots quicker than desired
115
Diseased states that can interfere with wound healing include:
Diabetes
Venous/arterial disease
Old age
Infection
116
List medication that are used to reduce/prevent blood coagulation (blood thinners)
(5)
1. Warfarin
2. Pradaxa
3. Xarelto
4. Eliquis
5. Plavix
117
Blood thinners are most commonly used in patients with previous
DVT
118
Warfarin competitively inhibits:
Vitamin K Epoxide Reductase Complex 1 (VKORC1)
119
Warfarin function by not allowing the epoxide to return back to:
Hydroquinone form
120
Warfarin can complete functional:
Vitamin K reserve
121
Warfarin can be neutralized by
High dose Vitamin K
122
Xarelto and Eliquis target:
Factors-Xa
123
Eliquis and Xarelto are competitive inhibitors of what factor
Factor-Xa
124
Factor-Xa is necessary for conversion of:
Prothrombin into thrombin
125
What drug directly inhibits thrombin
Pradaxa
126
X-linked recessive disorder that results in decreased factor-VIII
Hemophilia A
127
Hemophilia A can be treated with:
Recombinant factor-VIII
128
Known as Christmas disease, X-linked recessive disorder resulting in decreased factor-IX
Hemophilia B
129
Hemophilia B can be treated with
Recombinant factor IX
130
Who is prominent family that had hemophilia B
Queen Victoria
131
Enzyme that cleaves protein substrates into different parts
Protease
132
Trypsin prefers to cleave at what residues
Arginine and lysine
133
Trypsin is what type of protease
Serine
134
Activation of a zymogen commonly occurs by
Proteolytic cleavage
135
Protein kinases usually add phosphate to what amino acids in the side chains of proteins
Serine , threonine and tyrosine
136
Chemical compound that that sequesters calcium ions and draw it away for coagulation proteins
EDTA
137
Represent calcium binding sites on coagulation and bone proteins
GLA residues
138
Liquid phase of clothed blood after spinning out clot
Serum
139
Liquid phase of unclottted blood still containing clotting proteins (cells have centrifuged away)
Plasma
140
Inhibitor of cyclooxygenase which catalyzes formation of prostaglandin E2 and other prostaglandins and leukotrienes
Aspirin (NSAID)
141
Site of metabolism of fat soluble vitamin K
Gut bacteria
