Blood Coagulation And 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 4 steps to the coagulation process?
A
- Blood vessels constrict
- Activated platelets stick to injury site
- Platelets aggregate together & form plug
- Platelets and damage tissue release clotting factors
- Mesh of fibrin is formed (clot)
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 agonists
Platelet derived adhesion proteins
Plasma derived adhesion proteins
5
Q
What stage of hemostasis does the clotting cascade occur?
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 cleave 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 from the cleavage of fibrinogen (by thrombin) forms ____ at the site of injury?
A
Cross-linked fibrin mesh
11
Q
What occurs simultaneous 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 strands adhere to the plug to form a _____.
A
- Clotting factors
- Prothrombin -> thrombin
- Soluble fibrinogen—> insoluble fibrin
- Clot
13
Q
Platelet activation and its response:
A
Primary hemostasis
14
Q
When you have an exposed epithelium or ECM, this will cause the platelets to stick to ___.
A
Collagen
15
Q
The initial binding of the platelets to the exposed collagen makes them undergo a release reaction to release:
A
Von willebrand factor
16
Q
When von willebrand factor is released from 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 factor and GP1b the platelets that do stick will undergo a release reaction to secrete:
A
Serotonin, thromboxane A2, ADP
19
Q
Serotonin and thormboxane A2 stimulate:
A
Vasoconstriction
20
Q
When serotonin and thormboxane stimulate vasoconstriction this results in:
A
Reduced blood flow to the 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
Anuclear sacks 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)
Enterochromaffin cells
26
Thromboxane A2 is initially synthesized from:
Arachadonic acid
27
How does arachidonic acid form thormboxane A2?
Arachidonic acid—-> cyclooxygenase enzyme—-> Endoperoxidase—-> Thromboxane synthetase—-> thromboxane A2
28
Thromboxane A2 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:
Relaxation and contraction
33
Gp1b and GP1a, GP2b-3a are all
Glycoproteins
34
The initial activating event when platelets bind to Von Willebrand factor is mediated by:
GP1b
35
Firm adhesion of platelets to the subendothelia is mediated by:
GP2b-3a
36
What activates platelets?
GpVI
37
When platelet is resting describe the state of GP2b-3a complex
Not active
38
When platelet is activated, describe the state of GP2b-3a complex?
Activated - can now strongly bind
39
When the platelet is activated, why can GP2b-3a complex bind so strongly?
Because GP2b-3a undergoes a conformational change exposing new binding site for VFW or fibrinogen
40
The activated GP2b-3a that binds strongly to VWF promotes strong adhesion to the vessel wall, what part of aggregation is this?
Primary
41
Platelet aggregation is dependent upon _____ which allows a quicker activation and sustained response.
ADP
42
The clotting cascade involves how many pathways?
3
43
What pathway in the clotting cascade is activated by external trauma causing 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 facto VII
46
What clotting cascade pathway is activated by trauma inside the vascular system? (Activated by platelets, exposed endothelium, chemicals, or collagen)
Intrinsic pathway
47
What clotting cascade pathway has a slow response?
Intrinsic pathway
48
What clotting factors are involved in the intrinsic pathway?
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
The activated partial thromboplastin time measures:
The intrinsic pathway
52
The prothrombin time:
Measure the extrinsic pathway
53
In the coagulation cascade most of our factors exist in _____ forms and have 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 active on 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 residues
59
Thrombin, factor 7, factor 9 and factor 10 all contain a:
Uniquely modified glutamate residue
60
The uniquely modified glutamate residues on thrombin, factor 7, 9 and 10, will:
Anchor them on cell surface in a stable form
61
The uniquely modified glutamate residues (carboxyglutamate) on thrombin, factor 7,9 and 10, will undergo reactions that are dependent upon:
Vitamin K
62
Vitamin K is important in the:
Clotting cascade
63
What are the fat soluble vitamins?
ADEK
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 teh 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, and carboxylated prozymogen
68
In the carboxy glutamate reaction:
The vitamin K epoxide gets converted back into:
Vitamin K hydroquinone
69
In a carboxy glutamate reaction, the vitamin K epoxide gets converted back into the vitamin K hydroquinone via what two enzymes:
Vitamin K epoxide reductase and then 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, intrinsic, and common factors dependent on vitamin K?
Extrinsic: 7
Intrinsic: 9
Common: 10 and 2
72
If vitamin K levels are not adequate, factors II, VII, IX, and X cannot properly form:
A fibrin clot
73
What is the initial strength of the platelets inside 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 or factor 13
77
name the domains on the fibrin molecules:
Two D domains and 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 of fibrin
81
Peptide bonds between the domains of fibrin are created by:
Transglutaminase
82
We start with two fibrin molecules and the 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 is the fibrin mesh broken down by?
Plasmin
84
What is plasmin derived from?
Plasminogen
85
Further processing of plasmin gives rise to:
Krinkle proteins
86
Krinkle proteins are part of the:
Angiostatin molecule system
87
Plasmins main role in the 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 and Kallikrein
89
Inhibitors of plasminogen conversion to plasmin include:
Alpha 2 anti plasmin , and alpha2 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 4 sequential overlapping phases that include:
1. Hemostasis phase
2. Inflammatory phase
3. Proliferative phase
4. Remodeling phase
92
Within minutes post-injury, platelets aggregate at the injury site to form a fibrin clot which acts to control bleeding
Hemostasis
93
Bacteria and debris are phagocytoses and removed from the wound site. Factors are released that cause migration and division of cells involved in the proliferative phase.
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 is realigned along tension force lines and cells no longer need are removed by apoptosis- 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 both a regulator of platelet function and a mediator of hemostasis
Fibronectin
100
Fibronectin exists in what two forms?
Plasma form & 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 _______ protein.
ECM and scaffolding protein
103
What are two types of anticoagulants in blood tube?
Acid citrate dextrose solution & EDTA
104
How do the blood tube anticoagulants work?
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 stand 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 clots
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 factors VII, II (prothrombin), V, X, and fibrinogen
PT
110
The prothrombin time is measured in _____ and compared to a _____.
Seconds and normal range
111
Normal INR range
Below 1.1
112
INR of 2-3
Effective therapeutic range or mechanical heart valve
113
When the INR is higher than recommended range:
Means blood clots slowly
114
When INR is lower than the recommended range
Blood clots quicker than desired
115
Diseased states that can interfere with wound health I guess include:
DM, venous/arterial disease, old age, & infection
116
List the medications that are used to prevent/reduct 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 a hx of:
DVT
118
Warfarin competitively inhibits:
Vitamin K epoxide reductase complex 1 (VKORC1)
119
Warfarin functions by not allowing the epoxide to return back to:
Hydroquinone form
120
Warfarin can deplete functional:
Vitamin K reserves
121
Warfarin can be neutralized by:
High dose of vitamin K
122
Xarelto and Eliquis target what factor:
Factor Xa
123
Eliquis and Xarelto are competitive inhibitors of what factor?
Factor Xa
124
Factor Xa is necessary for conversion of:
Prothrombin —> thrombin
125
What drug directly inhibits thrombin?
Pradaxa
126
What is an X-linked recessive disorder that results in decreased factor VIII
Hemophilia A
127
Hemophilia A can be treated with:
Recombinant factor VIII
128
X-linked recessive disorder resulting in decreased factor IX known as Christmas disease
Hemophilia B
129
Hemophilia B can be treated with:
Recombinant factor IX
130
Who is prominent family that had hemophilia B?
Queen victorias family
131
Enzyme that cleaves protein substrates into different parts?
Protease
132
Trypsin prefers to cleave at what residues?
Argenine & lysine
133
What type of protease is trypsin?
Serine
134
Activation of a zymogen commonly occurs by:
Proteolytic cleavage
135
Protein kinases usually add phosphate to what amino acids on the side chains of proteins?
Serine, threonine, & tyrosine
136
Chemical compound that sequesters calcium ions and draws it always from coagulation proteins
EDTA
137
_____ represent calcium binding sites on coagulation proteins and bone proteins
GLA residues
138
Liquid phase of clotted blood after spinning out clot
Serum
139
Liquid phase of unclotted blood still containing clotting proteins (cells have been centrifuged away)
Plasma
140
Inhibitor of cyclooxygenase which catalyzes formation of prostaglandin E2 and other prostaglandins and other leukotrienes:
Aspirin (NSAID)
141
Where is a site of metabolism of fat soluble vitamin K
Gut bacteria
