PREFINAL LECTURE L2: NORMAL HEMOSTASIS Flashcards

(438 cards)

1
Q

ECs secrete VWF when activated by

A

vasoactive agents (e.g. thrombin)

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2
Q

Explain hemostasis book based

A

Hemostasis is a complex physiologic process that keeps circulating blood in a fluid state and then, when an injury occurs, produces a clot to stop the bleeding, confines the clot to the site of injury, and finally dissolves the clot as the wound heals.

(similar answer is acceptable)

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3
Q

When hemostasis system is out of balance, what 2 conditions could be life threatening?

A
  • Hemorrhage (uncontrolled bleeding)
  • Thrombosis (pathologic clotting)
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4
Q

The absence of a single plasma procoagulant
may destine the individual to what 3 lifelong consequences?

A
  • Anatomic hemorrhage
  • Chronic inflammation
  • Transfusion dependence
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5
Q

If this is absent, it would allow coagulation to proceed unchecked, and cause diseases such as thrombosis, stroke, pulmonary embolism, deep vein thrombosis, cardiovascular events.

A

control protein

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6
Q

Hemostasis involves the interaction of what 3 processes to stop bleeding?

A
  • Vasoconstriction
  • Platelet adhesion and aggregation
  • Coagulation enzyme activation
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7
Q

The key cellular elements of hemostasis are?

A
  • Cells of the vascular intima
  • Extravascular tissue factor (TF) bearing cells
  • Platelets
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8
Q

The plasma components/protein that play a role in hemostasis include the

(answer in general term)

A
  • Coagulation and fibrinolytic proteins
  • Their inhibitors
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9
Q

It refers to the role of blood vessels and platelets in the initial response to a vascular injury or to the commonplace desquamation of dying or damaged
endothelial cells.

A

Primary hemostasis

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10
Q

It describes the activation of a series of coagulation proteins in the plasma, mostly serine proteases, to form a fibrin clot.

A

Secondary hemostasis

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11
Q

End product of primary hemostasis

A

platelet plug formation

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12
Q

End product of secondary hemostasis

A

platelet clot

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13
Q

Based on table 35.1, identify if PRIMARY or SECONDARY hemostasis:

Procoagulant substances exposed or
released by damaged or activated
endothelial cells

A

primary hemostasis

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14
Q

Based on table 35.1, identify if PRIMARY or SECONDARY hemostasis:

The activator, tissue factor, is exposed on cell membranes

A

secondary hemostasis

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15
Q

Based on table 35.1, identify if PRIMARY or SECONDARY hemostasis:

Delayed, long-term response

A

secondary hemostasis

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16
Q

Based on table 35.1, identify if PRIMARY or SECONDARY hemostasis:

Rapid, short-lived response

A

primary hemostasis

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17
Q

Based on table 35.1, identify if PRIMARY or SECONDARY hemostasis:

Involves vascular intima and platelets

A

primary hemostasis

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18
Q

Based on table 35.1, identify if PRIMARY or SECONDARY hemostasis:

Involves coagulation system and platelets

A

secondary hemostasis

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19
Q

Based on table 35.1, identify if PRIMARY or SECONDARY hemostasis:

Activated by desquamation and
small injuries to blood vessels

A

primary hemostasis

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20
Q

Based on table 35.1, identify if PRIMARY or SECONDARY hemostasis:

Activated by large injuries to blood
vessels and surrounding tissues

A

secondary hemostasis

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21
Q

In primary hemostasis, the blood vessels contract for what purpose?

A
  • Seal the wound
  • Reduce the blood flow (vasoconstriction)
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22
Q

Arrange the following events in primary hemostasis:

A) Platelets secrete the contents of their granules
B) Platelets adhere to the site of injury
C) Platelets become activated
D) Platelets aggregate with other platelets to form a platelet
plug

A

C, B, A, D

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23
Q

Vasoconstriction and platelet plug formation comprise the initial, rapid, short-lived response to vessel damage. However, in order to control major bleeding in the long term, the plug must be reinforced by?

A

fibrin

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24
Q

Enumerate examples of defects in primary hemostasis.

A
  • Collagen abnormalities
  • Thrombocytopenia
  • Qualitative platelet disorders
  • von Willebrand disease
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25
Inactive form of coagulation factor
zymogens
26
In secondary hemostasis, coagulation proteins in the plasma, mostly serine proteases, circulate as what before coagulation?
Inactive zymogens (proenzymes)
27
Zymogens (proenzymes) that become activated during the process of coagulation, form complexes that activate other zymogens in order to ultimately generate what?
thrombin
28
What is thrombin?
an enzyme that converts fibrinogen to a localized fibrin clot
29
The final event of hemostasis is?
fibrinolysis
30
It is the gradual digestion and removal of the fibrin clot as healing occurs.
fibrinolysis
31
T/F: Coagulation and fibrinolysis are associated with primary hemostasis, while vascular intima and platelets are associated with secondary hemostasis
F (vascular intima and platelets = primary hemostasis, while coagulation and fibrinolysis = secondary hemostasis)
32
T/F: All systems in primary and secondary hemostasis interact in early- and late-hemostatic events.
T
33
Platelets secrete coagulation factors stored in their?
granules
34
Coagulation complexes form on the platelets' what?
cell membrane phospholipid
35
Term used to describe the entire network of blood vessels
vasculature
36
A blood vessel is structured into what 3 layers?
- Vascular intima - Vascular media - Vascular adventitia
37
Inner layer of blood vessel
vascular intima
38
Middle layer of blood vessel
vascular media
39
Outer layer of blood vessel
vascular adventitia
40
The vascular intima provides the interface between the?
circulating blood and the body tissues
41
The vascular intima of blood vessels is a monolayer of what metabolically active cells?
endothelial cells (ECs)
42
Supporting the endothelial cells in the vascular intima is the?
internal elastic lamina
43
The internal elastic lamina is composed of?
elastin and collagen
44
The subendothelial connective tissue of the vascular intima varies in veins and arteries. In arteries it is composed of?
- Collagen - Fibroblasts - Smooth muscle cells
45
The subendothelial connective tissue of the vascular intima varies in veins and arteries. In veins it is composed of?
Collagen and fibroblasts
46
Fibroblasts occupy the connective tissue layer and produce what protein in all blood vessels?
collagen
47
Smooth muscle cells in arteries and arterioles contract when an injury occurs and primary hemostasis is initiated, but not in the?
walls of veins, venules, or capillaries
48
The intact vascular endothelium prevents thrombosis through what 3 ways?
- Inhibiting platelet aggregation - Preventing coagulation activation and propagation - Enhancing fibrinolysis.
49
Give the 2 descriptions of the structure of ECs, which provide a smooth inner surface of the blood vessel, promotes even blood flow, and prevents harmful turbulence that otherwise may activate platelets and coagulation enzymes.
rhomboid and contiguous
50
ECs form a physical barrier separating what?
(1) Procoagulant proteins and platelets in blood from (2) collagen in the vascular intima, and (3) Tissue factor in fibroblasts and smooth muscle cells | these 3 layers are separated by ECs
51
Provide the anticoagulant property of this endothelial cell substance: prostacyclin
A platelet inhibitor and a vasodilator
52
Prostacyclin is synthesized through what pathway
eicosanoid pathway
53
Based on table 35.2, provide the ANTICOAGULANT property of this INTACT endothelial cell substance: ECs secrete nitric oxide
A vascular “relaxing” factor
54
Nitric oxide is synthesized in? Enumerate.
- ECs - Vascular smooth muscle cells - Neutrophils - Macrophages
55
Aside from smooth muscle relaxation, state other roles of nitric oxide
- Induces subsequent vasodilation - Inhibits platelet activation - Promotes angiogenesis and healthy arterioles
56
Provide the anticoagulant property of this endothelial cell substance: Tissue factor pathway inhibitor (TFPI)
Controls activation of the tissue factor pathway (aka the extrinsic coagulation pathway)
57
TFPI limits the activation of what specific complex?
TF:VIIa:Xa complex
58
What 2 known inhibitors of thrombin formation do ECs synthesize and express on their surfaces?
- Thrombomodulin facilitated by endothelial protein C receptor (EPCR) - Heparan sulfate
59
EPCR binds what protein?
protein C
60
Thrombomodulin catalyzes the ACTIVATION of what pathway?
protein C pathway
61
The protein C pathway downregulates coagulation by digesting what 2 factors, which thereby inhibits thrombin formation?
activated factors V and VIII
62
Based on table 35.2, provide the ANTICOAGULANT property of this INTACT endothelial cell substance: ECs secrete the glycosaminoglycan heparan sulfate
An anticoagulant that regulates thrombin generation
63
Heparan sulfate enhances the activity of which blood plasma serine protease inhibitor?
antithrombin
64
Based on table 35.2, provide the ANTICOAGULANT property of this INTACT endothelial cell substance: ECs secrete TPA
Activates fibrinolysis
65
TPA stands for
Tissue Plasminogen Activator
66
T/F: The pharmaceutical anticoagulant heparin RESEMBLES heparan sulfate of EC in structure and its inhibitory activity when bound to antithrombin.
T
67
TAFI stands for
Thrombin Activatable Fibrinolysis Inhibitor
68
If the INTACT endothelium has anticoagulant properties, DAMAGED vascular intima (ECs and subendothelial matrix) has what properties?
procoagulant properties
69
Arrange the following events: A) Collagen from subendothelial connective tissues binds and activates platelets. B) ECs secrete and coat themselves with P-selectin, and also secrete ICAMs and PECAMs C) ECs secrete von Willebrand factor when activated by vasoactive agents, and they also secrete ADAMTS13 D) EC disruption exposes TF in subendothelial cells and activates the coagulation system through contact with plasma coagulation factor VII, leading to fibrin formation E) Any harmful local stimulus, whether mechanical or chemical, induces vasoconstriction in arteries and arterioles
E, A, C, B, D
70
A flexible elastic structural protein
collagen
71
When collagen binds and activates platelets, it results to an initial platelet adhesion response, which fills in the damaged area until what?
until new ECs grow
72
Some connective tissue degeneration occurs naturally in aging. This can lead to what tendency in the elderly population?
increased bruising tendency
73
It is a large multimeric glycoprotein that acts as the necessary bridge that binds platelets to exposed subendothelial collagen in arterioles and arteries where blood flows rapidly
von-Willebrand factor (VWF)
74
VWF has been described as a “_______” since it spreads out, create sticky surface, and activated platelets assemble on it
carpet
75
function of ADAMTS13
cleaves LARGE VWF MULTIMERS into SHORTER CHAINS
76
An adhesion molecule that promotes platelet and leukocyte binding. ECs secrete and coat themselves with it.
P-selectin
77
ECs secrete what 2 immunoglobulin-like adhesion molecules?
ICAMs and PECAMs
78
ICAM stands for
intercellular adhesion molecules
79
PECAM stands for
platelet endothelial cell adhesion molecules
80
EC disruption activates the coagulation system through contact with which factor, leading to fibrin formation?
plasma coagulation factor VII
81
In pathologic conditions, TF may be expressed on what cells or molecules?
- Monocytes - Tissue factor-positive microparticles
82
TF may be expressed on monocytes during what specific conditions?
inflammation and sepsis
83
Tissue factor-positive microparticles are derived from?
- Membrane fragments of activated or apoptotic vascular cells - Surface of some ECs
84
It surrounds the platelet plug, securing it to the damaged area, such that the blood flow does not dislodge it.
fibrin
85
Excess arterial occlusion causes what diseases?
- Myocardial infarction - Stroke - Peripheral artery disease
86
Excess venous occlusion causes what diseases?
- Deep vein thrombosis - Thromboembolic disease
87
In veins, a bulky red clot is produced which consist of?
- Platelets - VWF - Fibrin - Red blood cells
88
Based on table 35.3, provide the PROCOAGULANT property of this DAMAGED vascular intima structure: Smooth muscle cells in arterioles and arteries
Induce vasoconstriction
89
Based on table 35.3, provide the PROCOAGULANT property of this DAMAGED vascular intima substance: Exposed subendothelial collagen
Binds VWF; binds to and activates platelets
90
Based on table 35.3, provide the PROCOAGULANT property of this DAMAGED vascular intima substance: Damaged or activated ECs secrete VWF
Important for platelet binding to collagen at site of injury: platelet adhesion as a first line of defense against bleeding
91
Based on table 35.3, provide the PROCOAGULANT property of this DAMAGED vascular intima substance: Damaged or activated ECs secrete adhesion molecules: P-selectin, ICAMs, PECAMs
Promote platelet and leukocyte binding and activation at site of injury
92
Based on table 35.3, provide the PROCOAGULANT property of this DAMAGED vascular intima structure: Exposed smooth muscle cells and fibroblasts
Tissue factor exposed on cell membranes
93
Based on table 35.3, provide the PROCOAGULANT property of this DAMAGED vascular intima structure: ECs in inflammation
Tissue factor is induced by inflammation
94
Fibrinolysis is the process of removing the fibrin to restore vessel patency, involving the secretion of?
tissue plasminogen activator (TPA)
95
During thrombus formation, these 2 binds to polymerized fibrin.
TPA and plasminogen
96
TPA activates fibrinolysis by
converting plasminogen to plasmin
97
ECs also regulate fibrinolysis by providing inhibitors to prevent excessive plasmin generation. State the inhibitors.
- Plasminogen Activator Inhibitor-1 (PAI-1) - Thrombin Activatable Fibrinolysis Inhibitor (TAFI)
98
A TPA control protein that inhibits plasmin generation and fibrinolysis
Plasminogen Activator Inhibitor-1 (PAI-1)
99
An inhibitor of plasmin generation, that is activated by thrombin bound to EC membrane thrombomodulin
Thrombin Activatable Fibrinolysis Inhibitor (TAFI)
100
Elevations in PAI-1 or TAFI can slow what process?
can slow fibrinolysis
101
Elevations in PAI-1 or TAFI can increase the tendency of what?
can increase the tendency for thrombosis
102
The diagnosis of blood vessel disorder is often based on
- Clinical symptoms - Family history - Laboratory tests that rule out platelet or coagulation disorders
103
Identify which among the 2 is the large molecule and the small molecule: - Platelet a-Granules - Platelet Dense Granules
Platelet a-Granules = large molecules Platelet Dense Granules = small molecules
104
Enumerate the Platelet α-Granules (large molecules)
- β-Thromboglobulin - Factor V - Factor XI - Fibrinogen - Protein S - Platelet factor 4 - Platelet-derived growth factor - VWF
105
Enumerate the Platelet Dense Granules (Small Molecules)
- Adenosine diphosphate - Adenosine triphosphate - Calcium - Serotonin
106
Among the Platelet Dense Granules, this molecule activates the neighboring platelets.
Adenosine diphosphate
107
Among the Platelet Dense Granules, this molecule acts as a vasoconstrictor.
serotonin
108
Plasma transports at least how many procoagulants?
at least 16 procoagulants
109
procoagulants are also called?
coagulation factors
110
Nearly all procoagulants are glycoproteins synthesized in what organ?
liver
111
Aside from the liver, a few amount of procoagulants are also produced in what cells?
- monocytes - ECs - megakaryocytes
112
Provide the name, function, and half-life (hr): Factor I
- Name: Fibrinogen - Function: Thrombin substrate, polymerizes to form fibrin - Half-Life (hr): 100-150
113
Provide the name, function, and half-life (hr): Factor II
- Name: Prothrombin - Function: Serine protease - Half-Life (hr): 60
114
Provide the name, function, and half-life (hr): Factor III
- Name: Tissue Factor - Function: Cofactor - Half-Life (hr): Insoluble
115
Provide the name, function, and half-life (hr): Factor IV
- Name: Ionic Calcium - Function: Mineral - Half-Life (hr): NA
116
Provide the name, function, and half-life (hr): Factor V
- Name: Proaccelerin/ Labile factor - Function: Cofactor - Half-Life (hr): 24
117
Provide the name, function, and half-life (hr): Factor VII
- Name: Stable factor/ Proconvertin/ Serum prothrombin conversion accelerator - Function: Serine Protease - Half-Life (hr): 6
118
Provide the name, function, and half-life (hr): Factor VIII
- Name: Antihemophilic factor - Function: Cofactor - Half-Life (hr): 12
119
Other name of Factor VIII or Antihemophilic factor
Platelet cofactor 1/ Antihemophilic factor globulin
120
Provide the name, function, and half-life (hr): VWF
- Name: von Willebrand factor - Function: Factor VIII carrier and platelet adhesion - Half-Life (hr): 24
121
Provide the name, function, and half-life (hr): Factor IX
- Name: Christmas factor - Function: Serine protease - Half-Life (hr): 24
122
Other name for factor IX or Christmas factor
Platelet cofactor 2/ Plasma thromboplasmin component
123
Provide the name, function, and half-life (hr): Factor X
- Name: Stuart-Prower factor - Function: Serine protease - Half-Life (hr): 48–52
124
Other name of factor X or Stuart-Prower factor
autoprothrombin III
125
Provide the function and half-life (hr): Factor XI
- Name: Plasma thromboplasmin antecedent/ Antihemophilic factor C - Function: Serine protease - Half-Life (hr): 48–84
126
Provide the name, function, and half-life (hr): Factor XII
- Name: Hageman factor - Function: Serine protease - Half-Life (hr): 48–70
127
Other name of factor XII or Hageman factor
Heydman factor/ Heydman stabilizer factor/ Glass factor
128
Provide the name, function, and half-life (hr): Prekallikrein
- Name: Fletcher factor, pre-K - Function: Serine protease - Half-Life (hr): 35
129
Provide the name, function, and half-life (hr): High-molecular-weight kininogen (HMWK)
- Name: Fitzgerald factor - Function: Cofactor - Half-Life (hr): 156
130
Provide the name, function, and half-life (hr): Factor XIII
- Name: Fibrin-stabilizing factor (FSF) - Function: Transglutaminase, transamidase - Half-Life (hr): 150
131
Provide the name and function Platelet factor 3
- Name: Phospholipids, phosphatidylserine, PF3 - Function: Assembly molecule
132
What are the 4 categories of plasma-based components of the coagulation system of blood clotting?
- Procoagulants (zymogens) - Cofactors - Anticoagulants (regulatory or control proteins) - Final fibrinogen substrate
133
Bind, stabilize, and enhance the activity of their respective enzymes.
Cofactor
134
The substrate for the enzymatic action of thrombin, and the primary enzyme of the coagulation system
Fibrinogen
135
Plasma glycoproteins that serve the important function of regulating the coagulation process to avoid unnecessary blood clotting.
Control proteins
136
In 1958, this committee officially named the plasma procoagulants using Roman numerals in the order of their initial description or discovery.
International Committee for the Standardization of the Nomenclature of the Blood Clotting Factors
137
When a procoagulant becomes activated, this character appears behind the numeral when written.
a lowercase "a" appears behind the numeral (e.g. activated factor VII is VIIa)
138
T/F: The factors are customarily identified by their roman numeral rather than their name
F | They're customarily identified by name rather than Roman numeral
139
The roman numeral VI, was assigned to a procoagulant that was later determined to be an activated form of what factor?
activated factor V (VI was withdrawn from the naming system and was never reassigned)
140
A cofactor that circulates while linked to a large carrier protein VWF.
Factor VIII (antihemophilic factor)
141
Prekallikrein and HMWK have never received Roman numerals because
They belong to the kallikrein and kinin systems, respectively, and their primary functions lie within these systems
142
Phosphatidylserine are required for the coagulation process but were given no Roman numeral; instead they were collectively called as
platelet factor 3
143
The coagulation factors work together in what type of pathway, where one factor when activated, activates the next factor in the sequence?
cascade pathway
144
The purpose of the cascade pathway is to generate what key enzyme? and produce what protein?
- generate key thrombin enzyme - produce fibrin
145
A localized thrombus
fibrin
146
These are proteolytic enzymes of the trypsin family.
Serine proteases
147
Enumerate the Inactive Zymogen
- Prothombin (II) - VII - IX - X - XI - XII - Prekallikrein
148
Enumerate the Active Protease
- Thrombin (IIa) - VIIa - IXa - Xa - XIa - XIIa - Kallikrein
149
The inactive zymogens are enzymes called what?
serine proteases
150
What factor is not a serine protease but a transglutaminase?
Factor XIII
151
What reactive amino acid residue is present in the active site of each member of the serine protease family?
reactive seryl amino acid residue
152
Serine protease acts on its substrate by hydrolyzing the?
peptide bonds | thus digesting the primary backbone of protein
153
The hydrolysis of peptide bonds and the digestion of the primary backbone of proteins leads to the production of what?
Small polypeptide fragments
154
Serine proteases are synthesized as inactive zymogens consisting of how many peptide chain?
a single peptide chain
155
Activation of inactive zymogens occur when what action is performed on the zymogen?
When it is cleaved at one or more specific sites
156
What cleaves the inactive zymogen at one or more specific sites?
the action of another protease during the coagulation process
157
Enumerate the substrates of thrombin (IIa)
- Fibrinogen - Factor V - Factor VIII - Factor XI - Factor XIII
158
Enumerate the cofactor and substrates of VIIa
C: Tissue factor S: Factor IX and Factor X
159
Cofactor and Substrate of IXa
C: Factor VIIIa S: Factor X
160
Cofactor and Substrate of Xa
C: Va S: Prothrombin
161
Substrate of XIa
Factor IX
162
Cofactor and Substrate of XIIa
C: HMWK S: Factor XI
163
Cofactor and Substrate of Kallikrein
C: HMWK S: Factor XI
164
The procoagulant cofactors that participate in complex formation are
- Tissue factor - Soluble plasma factors V, VIII, and HMWK
165
Tissue factors that participate in complex formation are located on the
- Membranes of fibroblasts - Smooth muscle cells
166
The remaining components of the coagulation pathway are
- Factor XIII - Phospholipids - Calcium - VWF | Labeled as "Other Plasma Procoagulants" in box 35.2
167
The ultimate substrate of the coagulation pathway.
Fibrinogen
168
Fibrinogen is primarily hydrolyzed by?
thrombin
169
T/F: fibrinogen is soluble while fibrin is insoluble
T
170
The insoluble structural protein of the fibrin clot is further stabilized by what factor?
factor XIIIa
171
# coagulation pathway #1 In the coagulation pathway, the exposed TF activates which factor?
Factor VII
172
# coagulation pathway #2 In the coagulation pathway, the activation of factor VII activates which factors?
factors IX and X
173
# coagulation pathway #3 In the coagulation pathway, this complex activates factor X
Factor IXa:VIIIa complex
174
# coagulation pathway #4 In the coagulation pathway, this complex activates prothrombin (factor II)
Factor Xa:Va complex
175
# coagulation pathway #5 In the coagulation pathway, the resulting thrombin cleaves fibrinogen to form what? and activate what?
to form fibrin to activate factor XIII
176
# coagulation pathway #6 In the coagulation pathway, the activation of factor XIII stabilizes the?
stabilizes the clot
177
# coagulation pathway #7 In the coagulation pathway, thrombin also activates which factors and cell, in a positive feedback loop?
- Factor V - Factor VIII - Factor XI - Platelet
178
# coagulation pathway #8 In the coagulation pathway, exposure to negatively charged surfaces (e.g., bacterial cell membranes) activates what?
- The contact factors XII - Prekallikrein (pre-K) - HMWK
179
# coagulation pathway #9 In the coagulation pathway, the activation of the contact factors XII, pre-K, and HMWK activates which factor?
Factor XI
180
This ion is required for the coagulation complexes that assemble on platelet or cell membrane phospholipids
Ionized calcium
181
Through what ions do serine proteases bind to negatively charged phospholipid surfaces?
Positively charged calcium ions
182
Which specific phospholipid is primarily involved in the binding of serine proteases?
phosphatidylserine
183
T/F: Coagulation activation is not a localized cell surface process, thus it is not limited to the site of injury.
F | It's a localized cell surface process,it's limited to the site of injury
184
They are dependent on vitamin K during synthesis to produce a functional structure. ENUMERATE
(Procoagulants↓) - Prothrombin (factor II) - Factors VII - Factor IX - Factor X (regulatory proteins↓) - Protein C - Protein S - Protein Z
185
Those that are dependent on vitamin K during synthesis are named the?
prothrombin group
186
Why is the prothrombin group called as such?
Because of their structural resemblance to prothrombin
187
All 7 proteins of the Prothrombin Group have how many glutamic acid units?
10 -12 glutamic acid units
188
The glutamic acid units of the Vitamin K-Dependent Prothrombin Group are located where?
near their amino terminal end
189
In the Vitamin K-Dependent Prothrombin Group, all are serine proteases when activated, except these 2
protein S and protein Z
190
protein S and protein Z are
cofactors
191
This vitamin is a quinone found in green leafy vegetables
Vitamin K
192
Vitamin K is produced by what intestinal organisms?
- Bacteroides fragilis - Escherichia coli
193
Vitamin K catalyzes an essential posttranslational modification of the prothrombin group proteins, called?
γ-carboxylation of amino-terminal glutamic acids
194
When a second carboxyl group is added to the γ carbon, glutamic acid is modified to?
γ-carboxyglutamic acid
195
With two ionized carboxyl groups, the γ-carboxyglutamic acids gain a net of what charge?
a net negative charge
196
With two ionized carboxyl groups, the γ-carboxyglutamic acids gain a net negative charge, which enables them to bind to?
ionic calcium
197
The bound calcium enables these vitamin K dependent coagulation factors to bind to
negatively charged phospholipids
198
The purpose of the binding of vitamin K dependent coagulation factors and negatively charged phospholipids is to?
form complexes with other coagulation factors.
199
A therapeutic inhibitor of vitamin K
Coumadin (anticoagulant drug)
200
The vitamin K-dependent procoagulants are released from the liver without the second carboxyl group added to the γ carbon, during what instances?
- Vitamin K deficiency - Presence of the anticoagulant drug Coumadin
201
The vitamin K-dependent procoagulants without the second carboxyl group added to the γ carbon are called?
des-γ-carboxyl proteins
202
Other name of des-γ-carboxyl proteins
Proteins Induced by Vitamin K Antagonists (PIVKA) factors
203
Why can't des-γ-carboxyl proteins participate in the coagulation reaction?
Because they cannot bind to calcium and phospholipid | due to lack of second carboxyl group
204
This is the basis for oral anticoagulant (warfarin, Coumadin) therapy
Vitamin K antagonism
205
Vitamin K-dependent procoagulants are essential for the assembly of how many membrane complexes?
3 membrane complexes
206
The assembly of 3 membrane complexes leads to the generation of what enzyme?
thrombin
207
Each membrane complex is composed of
- A vitamin K-dependent serine protease - Its nonenzyme cofactor - Calcium
208
The vitamin K-dependent serine protease, its nonenzyme cofactor, and calcium are bound to the negatively charged phospholipid membranes of?
- Activated platelets - TF-bearing cells
209
The initial complex called EXTRINSIC TENASE, is composed of?
- Factor VIIa - TF - Phopholipid - Calcium
210
Extrinsic tenase activates which factors?
factors IX and X
211
INTRINSIC TENASE is composed of?
- Factor IXa - and its cofactor VIIIa - Phospholipid - Calcium
212
Intrinsic tenase activates which factor?
Factor X
213
T/F: Intrinsic tenase activates factor X but the TF:VIIa complex is much more efficient
F | Intrinsic tenase is much more efficient than TF:VIIa complex
214
The complex Prothrombinase is composed of?
- Factor Xa - and its cofactor Va - Phospholipid - Calcium
215
Prothrombinase activates?
Prothrombin
216
In a multistep hydrolytic process, Prothrombinase converts prothrombin to?
thrombin
217
The conversion of prothrombin to thrombin in a multistep hydrolytic process releases thrombin and a peptide fragment called?
prothrombin fragment 1.2
218
Prothrombin fragment 1.2 in plasma is a marker for
thrombin generation
219
Each cofactor binds its particular serine protease. When bound to their cofactors, serine proteases gain what advantages?
stability and increased reactivity
220
Tissue factor is a transmembrane receptor for which factor?
factor VIIa
221
T/F: Under normal conditions, TF is not expressed on blood vessel cells.
T
222
Vessel injury exposes blood to the subendothelial TF-bearing cells and leads to activation of coagulation through which factor?
Factor VIIa
223
Does the activation of Factor VII rate limited by the injury itself?
Yes
224
TF is expressed in high levels in cells of what organs?
- Brain - Lung - Placenta - Heart - Kidney - Testes
225
T/F: In inflammatory conditions and sepsis, leukocytes and other cells can also express TF and initiate coagulation.
T
226
Are Factors V and VIII soluble plasma proteins?
Yes
227
During platelet activation and secretion, platelets release what factor at the site of injury?
partially activated factor V
228
The prothrombinase complex accelerates thrombin generation more than how many folds when compared with Xa alone?
300,000-fold
229
The initial small amount of thrombin generated activates what factor?
first factor V
230
Thrombomodulin-bound thrombin activates what protein?
protein C
231
Protein C inactivates which factor?
Factor Va (Va to Vi)
232
T/F: Factor V is both activated and then ultimately inactivated by the generation of thrombin
T
233
A mechanism for activating coagulation in conditions where foreign objects such as mechanical heart valves, bacterial membranes, or high levels of inflammation are present.
intrinsic contact factor complex
234
HMWK is a cofactor to what 2 plasma procoagulants, in the intrinsic contact factor complex?
factor XIIa and prekallikrein
235
A transmembrane protein constitutively expressed by vascular ECs, and a thrombin cofactor in the protein C pathway.
Thrombomodulin
236
Together, thrombomodulin and thrombin activate what protein?
Protein C | A coagulation regulatory protein
237
Once thrombin is bound to thrombomodulin, it loses what ability?
procoagulant ability to activate factors V and VIII
238
Activation of protein C, leads to destruction of which factors?
destruction of factors V and VIII
239
Destruction of factors V and VIII suppresses what?
further generation of thrombin
240
Destruction of factors V and VIII suppresses further generation of thrombin. What type of feeadback loop is this?
a negative feedback loop
241
Thrombin bound to thrombomodulin also activates what fibrinolysis inhibitor?
TAFI
242
Protein S is a cofactor to? 2 answers.
protein C and TFPI
243
Protein Z is a cofactor to what inhibitor?
Z-dependent protease inhibitor (ZPI)
244
Based on table 35.10, identify the cofactor's function and where it binds: TF
F: Procoagulant B: Factor VIIa
245
Based on table 35.10, identify the cofactor's function and where it binds: Factor V
F: Procoagulant B: Factor Xa
246
Based on table 35.10, identify the cofactor's function and where it binds: Factor VIII
F: Procoagulant B: Factor IXa
247
Based on table 35.10, identify the cofactor's function and where it binds: HMWK
F: Procoagulant B: Factor XII, prekallikrein
248
Based on table 35.10, identify the cofactor's function and where it binds: Thrombomodulin
F: Control (protein C) Antifibrinolytic (TAFI) B: Thrombin
249
Based on table 35.10, identify the cofactor's function and where it binds: Protein S
F: Control B: Protein C, TFPI
250
Based on table 35.10, identify the cofactor's function and where it binds: Protein Z
F: Control B: ZPI
251
Key proteins for hemostasis that are both critically involved in all protective mechanisms to avoid blood loss (i.e., platelets, vasculature, and blood coagulation leading to fibrin formation).
Factor VIII and VWF
252
Factor VIII is produced by
- Hepatocytes (primarily here) - Microvascular ECs in lung and other tissues
253
Is free factor VIII stable in plasma
NO it is unstable
254
Free factor VIII is unstable in plasma thus it circulates bound to
VWF
255
During coagulation, what does thrombin do to factor VIII?
cleaves factor VIII from VWF and activates it
256
Like factor Va, factor VIIIa is also inactivated by what protein?
protein C
257
Factor VIII and factor IX are the two plasma procoagulants whose production is governed by genes carried on what chromosome?
The X chromosome
258
Does Factor VIII deteriorates more slowly than the other coagulation factors in stored blood?
NO (it deteriorates more rapidly)
259
In thawed component plasma, the factor VIII level drops to approximately how many percent after 5 days?
drops to approximately 50%
260
VWF is composed of multiple subunits of how many daltons?
240,000 Daltons
261
The subunits of VWF are produced by which cells, where they combine to form multimers that range from 500,000 to 20,000,000 Daltons
ECs and megakaryocytes
262
ADAMTS13 stands for
A disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13
263
VWF has receptor sites for both
platelets and collagen
264
How does the VWF receptor sites for both platelets and collagen allows VWF to act as a bridge?
It binds platelets to exposed subendothelial collagen during platelet adhesion
265
The primary platelet surface receptor for VWF
GP Ib/IX/V
266
This sequence in VWF binds a second platelet receptor during platelet aggregation
Arginine-glycine-aspartic acid (RGD) sequence
267
The second platelet receptor
GP IIb/IIIa
268
Third site on the VWF molecule binds?
collagen
269
Fourth site on the VWF molecule binds?
factor VIII | the plasma procoagulant cofactor
270
VWF is the chaperone for what factor?
Factor VIII
271
2 common bleeding disorders
- Von Willebrand disease - Factor VIII deficiency
272
Levels of VWF vary by ABO blood type. What blood group have lower levels of VWF than any other blood group type?
Type O
273
T/F: VWF is an acute phase protein, as well as factor VIII
T
274
VWF and Factor VIII levels increase/decrease(?) in pregnancy, trauma, infection, and stress.
Increase
275
The “contact factors” are what 3 factors?
- Factor XII - HMWK (Fitzgerald factor) - Pre-K (Fletcher factor)
276
Contact factors are named as such because?
they are activated by CONTACT with negatively charged foreign surfaces
277
A glycoprotein that circulates bound to HMWK
pre-K
278
Factor XIIa transforms pre-K into?
its active form kallikrein
279
Kallikrein cleaves HMWK to form?
bradykinin
280
Factor XII and pre-K are zymogens that are activated to become?
serine proteases
281
Is HMWK an enzymatic cofactor?
NO (it is a nonenzymatic cofactor)
282
Name the complex: HMWK:pre-K:factor XIIa
contact factor complex
283
The contact factor complex activates what factor?
Factor XI
284
T/F: Deficiencies of factor XII, HMWK, or pre-K causes clinical bleeding disorders.
F (it does not cause clinical bleeding disorders)
285
Do deficiencies prolong laboratory tests and necessitate investigation?
YES
286
Factor XII is activated in vitro by surfaces with what charge?
negatively charged surfaces
287
Factor XII is activated in vitro by negatively charged surfaces, such as?
- non siliconized glass - kaolin - ellagic acid
288
Non siliconized glass, kaolin, ellagic acid are used as test reagents for?
the partial thromboplastin time (PTT, APTT) assay
289
In vivo, foreign materials such as stents, valve prostheses, and bacterial cell membranes activate contact factors, which can lead to?
thrombosis
290
Factor XI is activated by what complex and enzyme during coagulation?
- contact factor complex - thrombin (more significantly)
291
Deficiencies of factor XI can result in what level of bleeding?
mild and variable bleeding
292
syndrome with deficiency of factor XI
Rosenthal syndrome
293
Does the plasma levels of Factor XI correspond with degree of bleeding?
NO (it does not necessarily correspond with degree of bleeding)
294
Main enzyme of the coagulation pathway with multiple key activities.
Thrombin
295
Despite having multiple functions, the primary function of thrombin is?
cleave fibrinopeptides (FP) A and B from the α and β chains of the fibrinogen molecule
296
The cleavage of FP A and B from the α and β chains of the fibrinogen molecule triggers what? 2 answers
- Spontaneous fibrin polymerization - Beginning of fibrin clot
297
FPA and FPB are measurable in plasma and serve as a marker of
thrombin activation
298
Thrombin amplifies the coagulation mechanism by activating which cofactors?
V and VIII and factor XI
299
Thrombin activating cofactors V and VIII and factor XI, serves to generate what?
generate more thrombin | a positive feedback mechanism
300
Thrombin also activates factor XIII, which forms COVALENT BONDS between what domains of the fibrin polymer?
the D DOMAINS of the fibrin polymer
301
Thrombin activating factor XIII to form covalent bonds between the D domains of the fibrin polymer is to cross-link and stabilize what?
the fibrin clot
302
Does thrombin initiates aggregation of platelets?
YES
303
Thrombin bound to thrombomodulin activates the protein C pathway to suppress what process?
coagulation
304
Thrombin bound to thrombomodulin also activates TAFI to suppress what process?
fibrinolysis
305
Why is thrombin considered the key protease of the coagulation pathway?
Because of its multiple autocatalytic functions (It plays a role in coagulation (fibrin), platelet activation, regulation of coagulation activation (protein C), and controlling fibrinolysis (TAFI).)
306
The primary substrate of thrombin
fibrinogen
307
Fibrinogen is essential for platelet aggregation because it links activated platelets through their receptor called?
GP IIb/IIIa platelet fibrinogen receptor
308
The normal plasma concentration of fibrinogen ranges from how many mg/dL?
200 to 400 mg/dL
309
Is fibrinogen the most concentrated of all the plasma procoagulants?
YES
310
Is fibrinogen an APR?
YES
311
In the past, 2 coagulation pathways were described, both of which has this factor at the start of a common pathway. What is that factor?
activated factor X
312
In the past, coagulation experts identified the activation of what factor, as the primary step in coagulation?
factor XII
313
Why was the activation of factor XII identified as the primary step in coagulation in the past?
because factor XIIa could be found in blood, whereas TF could not
314
The reaction system that begins with factor XII and culminates in fibrin polymerization has been called the?
Intrinsic pathway
315
Enumerate the coagulation factors of the intrinsic pathway, in order of reaction.
- Factor XII - pre-K - HMWK - Factor XI - Factor IX - Factor VIII - Factor X - Factor V - Prothrombin (II) - Fibrinogen
316
The laboratory test that detects the absence of one or more of the factors involved in the intrinsic pathway is the?
activated partial thromboplastin time (APTT or PTT)
317
T/F: The contact system establishes a connection between inflammation and coagulation activation.
T
318
The formation of this complex has since proven to be the primary in vivo initiation mechanism for coagulation.
TF:VIIa
319
TF pathway other name?
extrinsic pathway
320
TF pathway has been called the extrinsic pathway because?
TF is not present in blood
321
Extrinsic pathway includes which factors?
- Factors VII - Factor X - Factor V - prothrombin - Fibrinogen
322
The test used to measure the integrity of the extrinsic pathway is the?
prothrombin time (PT)
323
These tests are assays often used in tandem to screen for coagulation factor deficiencies
PT and PTT
324
This test is used to monitor heparin therapy
APTT
325
This test is used to monitor warfarin therapy
PT
326
Why are Factor VIII and Factor IX not considered to be part of the extrinsic pathway?
Because the PT fails to identify their absence or deficiency
327
This complex in the intrinsic pathway is crucial to the activation of factor X
IXa:VIIIa complex
328
The 2 pathways (extrinsic and intrinsic) common factors are?
- Factor X - Factor V - prothrombin - fibrinogen
329
The intrinsic and extrinsic pathways common factors are X, factor V, prothrombin, and fibrinogen. This portion of the coagulation pathway is often called as what pathway?
common pathway
330
T/F: Intrinsic, extrinsic, and common—are used extensively to interpret IN VITRO laboratory testing of blood plasma and to identify factor deficiencies. They also describe the complex interdependent reactions that occur IN VIVO.
F (they do not adequately describe the complex interdependent reactions that occur in vivo)
331
T/F: The extrinsic and intrinsic pathways are not distinct, independent, alternative mechanisms for generating thrombin but are actually INTERDEPENDENT
T Example: [1] deficiency of factor VII in the extrinsic pathway can cause significant bleeding, even when the intrinsic pathway is intact [2] deficiencies of factors VIII and IX may cause severe bleeding, regardless of the presence of a normal extrinsic pathway
332
Intrinsic pathway doesn't involve what type of injury?
trauma type injury
333
Initiation of intrinsic pathway
Damaged blood vessel
334
In addition to procoagulant and anticoagulant plasma proteins, normal physiologic coagulation requires the presence of what 2 cell types, for the formation of coagulation complexes?
- Cells that express TF (usually extravascular) - Platelets (intravascular)
335
Coagulation can be described as occurring in what 2 phases?
initiation and propagation phases
336
This phase occurs on tissue factor-expressing cells and produces 3% to 5% of the total thrombin generated.
Initiation phase
337
This phase occurs on platelets, which produces 95% or more of the total thrombin.
propagation phase
338
In vivo, the principle mechanism for generating thrombin is begun by the formation of what complex?
extrinsic tenase complex
339
This phase refers to the extrinsic tenase complex formation and generation of small amounts of factor Xa, factor IXa, and thrombin
The initiation phase
340
T/F: The magnitude of the localized response depends largely on the extent of the injury, such as how large the bleed is, how much tissue is damaged, and how many platelets are available.
T
341
About how many percent of factor VIIa is present normally in blood in the activated form?
About 1% to 2%
342
Factor VIIa is inert until bound to?
TF
343
Factor VIIa is unaffected by?
TFPI and other inhibitors
344
Factor VIIa binds to TF on the membrane of subendothelial cells, to form what complex?
the extrinsic tenase complex TF:VIIa
345
TF:VIIa activates low levels of what 2 factors?
factor IX and factor X
346
A minute amount of thrombin is generated by
- membrane-bound Xa - Xa:Va prothrombinase complexes
347
The initial minute amount of thrombin generates feedback to the coagulation cascade, in order to activate which plasma factors?
- Factors V - Factor VIII - Factor XI
348
The activation of plasma factors V, VIII, and XI serves to amplify what?
Amplify more thrombin generation
349
Coagulation complexes bound to cell membranes are relatively protected by most inhibitors from being what?
inactivated
350
If Xa:Va complex dissociates from the cell, it is rapidly inactivated by?
- protease inhibitors TFPI - Antithrombin - ZPI
351
If Xa:Va dissociates from the cell, it is rapidly inactivated by protease inhibitors TFPI, antithrombin, and ZPI until what?
until a threshold of Xa:Va activity is reached
352
The amount of thrombin generated in initiation phase is small/large(?)
small
353
T/F: Even though the amount of thrombin generated in initiation phase is small, the platelets, cofactors, and procoagulants become activated.
T
354
What does the low level of thrombin generated in the initiation phase do:
(1) activates platelets through cleavage of protease activated receptors PAR-1 and PAR-4 (2) activates factor V released from platelet a-granules (3) activates factor VIII and dissociates it from VWF (4) activates factor XI, the intrinsic accessory procoagulant that activates more factor IX (5) splits fibrinogen peptides A and B from fibrinogen and forms a preliminary fibrin network. The initial platelet is thus formed
355
Cleavage of fibrinopeptides from the fibrinogen molecule occurs at which part of the initiation and propagation phase?
- End of the initiation phase - Beginning of the propagation phase
356
More than how many percent of thrombin generation occurs during propagation?
more than 95% of thrombin generation
357
In this phase the reactions occur on the surface of the activated platelet, which now has all the components needed for coagulation.
propagation phase
358
Platelets are activated at the site of injury by both the?
- Low level thrombin generated in the initiation phase - Exposed collagen
359
Platelets partially activated by collagen and thrombin are referred to as?
COAT platelets
360
Partially activated COAT platelets have a lower/higher(?) level of procoagulant activity than platelets exposed to collagen alone.
HIGHER level of procoagulant activity
361
The cofactors Va and VIIIa activated by thrombin in the initiation phase bind to?
platelet membranes
362
The cofactors Va and VIIIa bind to platelet membranes, and become receptors for what factors?
factors Xa and IXa
363
IXa generated in the initiation phase binds to what factor on the platelet membrane?
factor VIIIa
364
IXa generated in the initiation phase binds to VIIIa on the platelet membrane to form what complex?
intrinsic tenase complex IXa:VIIIa
365
Does platelet-bound factor XIa generate more factor IXa ?
YES
366
The intrinsic tenase complex activates factor X at how many folds higher than the extrinsic tenase complex?
50- to 100-fold higher rate
367
Factor Xa binds to Va to form what complex?
prothrombinase complex
368
What does prothrombinase complex do?
activates prothrombin and generates a burst of thrombin
369
What procoagulant factor stabilizes the clot?
Factor XIII
370
Factor XIII is activated by?
thrombin
371
What pathway is activated when thrombin binds to thrombomodulin?
protein C control pathway
372
What inhibitor does thrombin activates to inhibit fibrinolysis?
TAFI
373
They prevent clotting from spreading to other parts of the body. 2 answers.
Protease inhibitors and intact endothelium
374
4 regulatory functions of inhibitors, or natural anticoagulants
- Slow the activation of procoagulants - Suppress thrombin production - Ensure that coagulation is localized and is not a systemic response - Prevent excessive clotting or thrombosis
375
The principal regulators of coagulation
- TFPI - Antithrombin (AT) - Activated protein C (APC).
376
Acquired or inherited deficiencies of TFPI, antithrombin (AT), and activated protein C (APC), may be associated with increased incidence of what disease?
venous thromboembolic disease (because the hemostatic balance is shifted toward increased thrombin generation and coagulation)
377
A Kunitz-type serine protease inhibitor and is the principal regulator of the TF pathway.
TFPI (Tissue Factor Pathway Inhibitor)
378
What kunitz binds to and inhibits factor Xa?
Kunitz-2 domain
379
What kunitz binds to and inhibits the VIIa:TF complex?
Kunitz-1
380
TFPI is primarily synthesized primarily by what cells?
ECs
381
Aside form ECs, TFPI is also expressed on what cells?
platelets
382
In the initiation of coagulation, what factors combine to activate factors IX and X?
factor VIIa and TF
383
TFPI inhibits coagulation in how many steps?
two-step process
384
First step of TFPI to inhibit coagulation.
binding and inactivating Xa
385
2nd step of TFPI to inhibit coagulation.
The TFPI:Xa complex binds to TF:VIIa
386
What type of complex is formed when TFPI:Xa and TF:VIIa binds?
a quaternary complex
387
What does the quaternary complex of TFPI do?
prevent further activation of X and IX
388
Can TFPI bind to Factor Xa if Xa is already in the TF:VIIa:Xa complex?
yes
389
T/F: TFPI provides feedback inhibition because it is not actively engaged until coagulation is initiated and factor X is activated.
T
390
Protein S is the cofactor of which 2 principal regulators?
APC and TFPI
391
Protein S enhances what inhibitory actrion?
Factor Xa inhibition of TFPI
392
The TF:VIIa:Xa reaction is short lived because of?
Because of the inhibitory action of TFPI
393
What will happen once TFPI shuts down the extrinsic tenase complex and Xa?
Additional Xa and IXa production shifts to the intrinsic pathway.
394
During which phase of coagulation, does factor X activation by IXa:VIII and additional factor IX activation by XIa occur?
propagation phase
395
Based on table 35.11, provide the function and half-life(hr) of this coagulation regulatory protein: TFPI
F: With Xa, binds TF:VIIa H-L: Unknown
396
Based on table 35.11, provide the function and half-life(hr) of this coagulation regulatory protein: Thrombomodulin
F: EC surface receptor for thrombin H-L: Does not circulate, although soluble truncated forms can be measured
397
Based on table 35.11, provide the function and half-life(hr) of this coagulation regulatory protein: Protein C
F: Serine protease H-L: 7–9
398
Based on table 35.11, provide the function and half-life(hr) of this coagulation regulatory protein: Protein S
F: Cofactor H-L: Unkown
399
Based on table 35.11, provide the function and half-life(hr) of this coagulation regulatory protein: Antithrombin
F: Serpin (Serine protease inhibitor) H-L: 68
400
Based on table 35.11, provide the function and half-life(hr) of this coagulation regulatory protein: Heparin cofactor II
F: Serpin (Serine protease inhibitor) H-L: 60
401
Based on table 35.11, provide the function and half-life(hr) of this coagulation regulatory protein: Protein Z-dependent protease inhibitor
F: Serpin H-L: Unknown
402
Based on table 35.11, provide the function and half-life(hr) of this coagulation regulatory protein: Protein C inhibitor
F: Serpin H-L: 23
403
Based on table 35.11, provide the function and half-life(hr) of this coagulation regulatory protein: a1-Protease inhibitor (a1-antitrypsin)
F: Serpin H-L: Unknown
404
Based on table 35.11, provide the function and half-life(hr) of this coagulation regulatory protein: a2-Macroglobulin
F: Serpin H-L: 60
405
In intact normal vessels, where coagulation would be inappropriate, thrombin avidly binds to what EC membrane protein?
thrombomodulin
406
Thrombin binding to thrombomodulin triggers an essential coagulation regulatory system called the?
protein C system
407
The protein C system revises thrombin’s function from a procoagulant enzyme to?
anticoagulant
408
A transmembrane protein that binds protein C adjacent to the thrombomodulin-thrombin complex.
EC protein C receptor (ECPR)
409
EPCR augments the action of the thrombin-thrombomodulin of at least how many folds, in activating protein C to the serine protease APC?
atleast fivefold
410
When the activated form of protein C dissociates from EPCR, it binds to its cofactor which is the?
free plasma protein S
411
The stabilized APC-protein S complex hydrolyzes and inactivates which factors?
factors Va and VIIIa
412
Protein S is synthesized in what organ?
liver
413
Protein S circulates in the plasma in how many forms?
2 forms
414
2 forms of protein S
- Free plasma protein S is free - Protein S that covalently bound to the complement control protein C4b-binding protein (C4bBP)
415
About how many percent of protein S is free?
about 40%
416
About how many percent of protein S is covalently bound to the complement control protein C4b-binding protein (C4bBP)?
about 60%
417
T/F: Bound protein S can participate in the protein C anticoagulant pathway
F (it cannot participate)
418
T/F: Bound protein S and free plasma protein S can both serve as the APC cofactor
F | only free plasma protein S can serve as the APC cofactor
419
Protein S-C4bBP binding is of particular interest in what conditions?
inflammatory conditions
420
Why is the binding of protein S to C4b-binding protein (C4bBP) particularly relevant in inflammatory conditions?
because C4bBP is an acute phase reactant
421
What happens to free protein S levels when plasma C4b-binding protein (C4bBP) levels increase?
free protein S levels become proportionally decreased | because more protein S is bound
422
More bound protein S and proportionally decreased level of free protein S may increase the risk of?
thrombosis
423
A vitamin K-dependent plasma glycoprotein that is synthesized in the liver
protein Z
424
cofactor of ZPI
protein Z
425
what does ZPI inhibit?
factor Xa
426
ZPI inhibits factor Xa with the help of what substances
protein Z, Ca, and phospholipids
427
Which serpins are involved in coagulation and fibrinolysis?
- ZPI - protein C inhibitor - α1-protease inhibitor - α2-macroglobulin - α2-antiplasmin - PAI-1
428
T or F: There is a delicate balance between the activators and inhibitors in fibrinolysis
T
429
T or F: fibrinolytic process is activated in response to inflammation and coagulation
T
430
when is the fibrinolytic process activated
several hours after fibrin polymeration and thrombus formation
431
what happens to fibrinolytic proteins to concentrate and localize fibrinolysis to the site of injury?
it becomes incorporated into the fibrin clot
432
final stage of hemostatic activation
fibrinolysis
433
Suppresses fibrinolysis by removing firbin C-terminal lysine binding sites blocking TPA and plasminogen binding
TAFI
434
difference of TPA and UPA
TPA: secreted by activated endothelium UPA: kidney cells
435
secreted by endothelium, inhibits tissue plasminogen activator
plasminogen activator inhibitor-1 (PAI-1)
436
define plasminogen
inactive form of plasmin
437
activates plasminogen
tissue plasminogen activator and urokinase plasminogen activator
438