Unit 9 - Coagulation Flashcards
1
Q
tunica media is thicker in arteries or veins?
A
arteries
2
Q
thinnest vascular layer in veins
A
tunica externa
3
Q
how does the body attempt to prevent hemorrhage with vascular injury?
A
- vascular spasm
- formation of platelet plug
- coagulation and fibrin formation
- fibrinolysis when clot no longer needed
4 steps of homeostasis
4
Q
primary step of homeostasis
A
formation of platelet plug
5
Q
function of von willebrand factor
A
platelet adhesion
6
Q
function of collagen
A
tensile strength
7
Q
function of fibronectin
A
cell adhesion
8
Q
function of thrombomodulin
A
regulates naturally occuring anticoagulants
9
Q
function of protein C
A
degrades factor 5a & 8a
10
Q
degrades factor 5a & 8a
A
protein C
11
Q
cofactor for protein C
A
protein S
12
Q
degrades factors 9a, 10a, 11a, 12a
A
antithrombin
13
Q
function of antithrombin
A
degrades factors 9a, 10a, 11a, 12a
14
Q
precursor to plasmin
A
plasminogen
15
Q
activates plasmin
A
tPA
urokinase
16
Q
inactivates tPA & urokinase
A
alpha-antiplasmin
17
Q
inhibits plasmin
A
plasmin activator inhibitor
18
Q
vasoactive mediators responsible for vascular smooth muscle constriction
A
thromboxane A2
ADP
serotonin
19
Q
vasoactive mediators responsible for vascular smooth muscle relaxation
A
nitric oxide
prostacyclin
20
Q
produces platelets in bone marrow
A
megakaryocytes
21
Q
where are platelets produced
A
bone marrow
by megakaryocytes
22
Q
normal platelet value
A
150-300k
23
Q
lifespan of a platelet
A
8-12 days
24
Q
how are platelets cleared
A
by macrophages in reticuloendothelium & spleen
25
what organ can sequester up to 1/3 of all circulating platelets for later use
spleen
26
why are plts pushed towards vessel wall close to site of action
smaller size
27
where do glycoproteins adhere
injured endothelium, collagen, and fibrinogen
28
2 components of platelet external membrane
glycoproteins
phospholipids
29
7 components inside the plts
1. actin/myosin
2. thrombosthenin
3. ADP
4. calcium
5. fibrin-stabilizing factor
6. serotonin
7. growth factor
30
function of actin & myosin inside platelet
help contract to form plt plug
31
function of thrombosthenin inside the platelet
help with platelet activation & aggregation
32
function of ADP inside platelet
plt activation & aggregation
33
function of calcium inside platelet
multiple functions in coagulation cascade (factor 4)
34
function of serotonin inside plts
activates nearby plts
35
function of growth factor inside platelet
helps repair damaged vessel walls
36
what keeps blood as a liquid when there's no injury
1. coagulation proteins circulate in inactive form
2. glycocalyx repels clotting factors
3. smooth endothelium prevents activation of plts/coagulation
4. activated factors removed by brisk blood flow/circulating anticoagulants
37
how does the endothelium inhibit plt function in the absence of vascular injury
secretes prostaglandin 12 & nitric oxide
38
substrate for prostaglandin synthesis
phospholipids
39
what produces thromboxane A2
phospholipids
40
what does the GpIIb complex do
* attaches activated platelet to vWF
* links platelets together to form plug
41
how does nitric oxide inhibit platelet function
inhibits thromboxane A2 receptor
42
how does prostaglandin 12 help inhibit plt function
* inhibits vWF adherence
* thromboxane A2 activation
* release of storage granules
43
common sources of endothelial injury
* surgery
* trauma
* plaque dislodgment
* spontaneous micro-injury (occur daily)
44
what part of the vessel contracts immediately following injury
tunica media
45
tunica media contraction with injury is the result of what 3 functions
1. SNS reflexes
2. myogenic response
3. release of vasoactive substances
46
2 functions of vascular spasm
1. reduces blood loss
2. helps procoagulants remain in affected area
47
3 steps of primary homeostasis
1. adhesion
2. activation
3. aggregation
48
how long does the process to form a plt plug take
about 5 min
49
what happens in step 1 of platelet plug formation
adhesion
plts immediately adhere to exposed collagen with help of vWF
| endothelial injury exposes collagen
50
how do plts adhere to collagen in step 1 of primary homeostasis
via Gp Ia/IIa and Gp VI receptors
51
how long does it take for platelets to adhere to collagen after vascular injury
within seconds
52
where is von Willebrand factor synthesized and released from
endothelium
53
where does vWF bind to platelet to bind to subendothelium
to GpIb receptor
54
step 2 of primary homeostasis
| (formation of plt plug)
plts contract and release series of compounds that attract other plts to site
55
how are platelets activated in step 2 of primary homeostasis
exposed collagen at site of injury activates plts
56
2 substances released by activated platelets
ADP
thromboxane A2
57
responsible for adhering platelet to damaged vessel
von willebrand factor
58
what do activated plts release in step 2 of primary homeostasis
contents of alpha granules
* fibrinogen
* fibronectin
* vWF
* platelet factor 4
* platelet growth factor
59
2 glycoproteins expressed on surface of activated platelets
GpIIb
GpIIIa
60
links activated platelets together to form platelet plug
GpIIb/IIIa receptor complex
61
step 3 of primary homeostasis
**aggregation**
plt plug forms
62
required to configure GpIIb and GpIIIa
Thromboxane A2
ADP
63
what is needed to mesh wound in micro-injuries
a platelet plug is all that's needed
(activation of coagulation cascade not needede)
64
primary purpose of coagulation cascade
form fibrin
65
in the classic coagulation model, when is the extrinsic pathway activated
when coagulation initiated outside intravascular space
66
in the classic coagulation model, when is the intrinsic pathway activated
when coagulation initiated inside intravascular space
67
how is coagulation activated in the cell based model
by extrinsic pathway as injured endothelium releases tissue factor 3
68
endpoint of classic model of coagulation
2 distinct pathways
each arrives st final common pathway
69
function of intrinsic pathway in cell based model
amplifies thrombin generating effect of extrinsic pathway
70
factors in coagulation cascade
1 fibrinogen
2 prothrombin
3 tissue factor
4 calcium ions
5 labile factor
7 stable factor
8 antihemophilic factor
9 christmas factor
10 stuart-prower factor
11 plasma thromboplastin antecedant
12 hageman factor
13 fibrin stabilizing factor
## Footnote
Foolish People Tty Climbing Long Slopes After Christmas Some People Have Fallen
70
factors in coagulation cascade
1 fibrinogen
2 prothrombin
3 tissue factor
4 calcium ions
5 labile factor
7 stable factor
8 antihemophilic factor
9 christmas factor
10 stuart-prower factor
11 plasma thromboplastin antecedant
12 hageman factor
13 fibrin stabilizing factor
## Footnote
Foolish People Tty Climbing Long Slopes After Christmas Some People Have Fallen
71
where are factors in coagulation cascade synthesized
liver
except tissue factor (vascular wall) & calcium (diet)
72
lab test for intrinsic pathway
PTT, ACT
73
lab tests for extrinsic pathway
PT/INR
74
vitamin-k dependent clotting factors
2, 7, 9, 10
75
1st coagulation factor activated in extrinsic pathway
tissue factor
76
activates extrinsic pathway
tissue factor
77
factors of extrinsic pathway
3 & 7
78
first factor to become deficient in liver failure, vitamin K deficiency, and pts on warfarin
factor 7
79
coagulation factor with the shortest half life
factor 7
(4-6 hours)
80
how much time does extrinsic pathway take
~15 seconds
81
collective coagulation factors that lead to thrombin activation (2a)
prothrombin activator
aka prothrombinase
82
how is factor 10 activated in extrinsic pathway
* tissue trauma activates tissue factor
* tissue factor activates factor 7
* factor 7 activates factor 10 in presence of 4 calcium
83
positive feedback mechanism that accelerates continued production of prothrombin activator in extrinsic pathway
factor 5
84
factors specific to classical intrinsic pathway
8, 9, 11, 12
85
steps of extrinsic pathway
1. tissue factor release
2. factor 10 activation
3. prothrombin activator
86
steps of intrinsic pathway
1. blood trauma exposure to collagen
2. factor 11 activation
3. factor 9 activation
4. factor 10 activation
5. prothrombin activator
87
time for intrinsic pathway to form a clot
6 minutes
88
what happens in first step of intrinsic pathway
blood trauma exposure to collagen = factor 12 activation
89
how is factor 11 activated in intrinsic pathway
factor 12a
90
what is required for factor 12a to activate factor 11 in intrinsic pathway
HMW kininogen
91
what acceperates factor 12a activation of factor 11
prekallikrein
92
what activates factor 9 in intrinsic pathway
factor 11
93
how is factor 10 activated in intrinsic pathway
by factor 9a & 8
94
what factor is missing in hemophilia A
8
95
how is thrombin (factor 2a) activated in intrinsic pathway
prothrombin activator & tissue phospholipids
| identical to last step of extrinsic pathway
96
how is thrombin (factor 2a) activated in intrinsic pathway
prothrombin activator & tissue phospholipids
| identical to last step of extrinsic pathway
97
factors involved in final common pathway
5, 10, 1, 2, 13
## Footnote
"The final common pathway can be purchased at the five (5) and dime (5) for 1 or 2 dollars on the 13th of the month"
97
factors involved in final common pathway
5, 10, 1, 2, 13
## Footnote
"The final common pathway can be purchased at the five (5) and dime (5) for 1 or 2 dollars on the 13th of the month"
98
factors involved in final common pathway
5, 10, 1, 2, 13
## Footnote
"The final common pathway can be purchased at the five (5) and dime (5) for 1 or 2 dollars on the 13th of the month"
99
primary goals of intrinsic and extrsinic pathway in final common pathway
produce prothrombin activator
100
when does final common pathway begin
when prothrombinase (complex of 10z + 5a + 4) converts prothrombin (2) to thrombin (2a)
101
proteolytic enzyme that changes fibrinogen to fibrinogen monomer
thrombin (2a)
102
when is fibrin incorporated into platelet plug in final common pathway
after platelets aggregate
103
facilitates cross-linkage of fibin fibers to complete clot in final common pathway
factor 13a
activated fibrin-stabilizing factor
104
4 mechanisms that counterbalance clot formation
1. vasodilation/washout of ADP & TXA2
2. anththrombin actions
3. tissue factor pathway inhibitor
4. protein C & S
105
how does antithrombin counterbalance clot formation
inactivates thrombin (2a), 9a, 10a, 11a, & 12a
106
how do proteins C & S counterbalance clot formation
inhibit factors 5a and 8a
107
where is plasminogen synthesized
liver
108
function of plasminogen
proenzyme incorporated into clot as it's being formed (dormant until activated)
109
what is plasmin
proteolytic enzyme that degrades fibrin into fibrin degradation products
110
2 enzymes that convert plasminogen to plasmin
tPA
urokinase
111
major mechanism of plasmin activation
injured tissue releases tissue plasminogen activator (tPA) over a period of days
112
minor mechanism of plasmin formation
urokinase produced by kidneys and released into circulation
113
where is urokinase produced
kidneys
114
how are plasmin activators used therapeutically
to dissolve thrombi and restore blood flow
115
inhibits conversion of plasminogen to plasmin
tPA inhibitor (tPAI)
116
inhibits action of plasmin on fibrin
alpha-2 antiplasmin
117
3 phases of contemporary cell-based coagulation cascade
1. initiation
2. amplification
3. propagation
118
when does the initiation phase of the contemporary coagulation cascade begin
when tissue factor is expressed
119
what factors begin the initiation phase of contemporary coagulation cascade
3 & 7
120
thrombin levels during initiation phase of contemporary coagulation cascade
remain low bc tissue factor pathway inhibitor limits amount of tissue factor released
121
why isn't fibrin activated in the initiation phase of the contemporary coagulation cascade
quantity of thrombin produced is insufficient to activate thrombin
122
lays groundworn for large-scale thrombin production in amplification phase of contemporary coagulation cascade
platelets and cofactors
123
how does the small amount of thrombin produced on TF-bearing cells amplify the coagulation response
(contemporary coagulation cascade)
by activating platelets, factor 5, and factor 11
124
what happens in the propagation phase of the contemporary coagulation cascade
Large quantities of thrombin are produced on the surfaces of platelets
125
when does propagation phase begin (contemporary coagulation cascade)
factor 10 is activated by factors 4 (Ca+2), 8, and 9 on the surface of the platelet
126
which phase of contemporary coagulation cascade is a positive feedback mechanism
propagation phase
| produces enough thrombin to activate fibrin
127
which phase of contemprary coagulation cascade is a positive feedback mechanism
propagation phase
| produces enough thrombin to activate fibrin
128
what coagulation pathways does aPTT assess
intrinsic
final common
129
best predictor of bleeding during surgery
history & physical
130
what does aPTT measure
time it takes to form a clot using phospholipid, calcium, and an activator
131
Monitors therapeutic response to **unfractionated heparin** (not LMWH)
aPTT
132
factors included in intrinsic pathway
12
11
9
8
133
coagulation pathway inhibited by heparin
intrinsic
134
what is the role of thrombin
converts fibrinogen to fibrogen monomer
135
what must be present to convert fibrogen monomer to fibrin fibers
calcium (factor 4)
136
converts fibrin to fibrin degredation products
plasmin
137
measures fibrin degradation products
D-dimer
138
inhibits conversion of plasminogen to plasmin
tPA
139
normal aPTT value
25-32 seconds
140
why is normal aPTT longer than normal PT
the intrinsic pathway is slower than extrinsic
141
at what point will a change in aPTT occur
factors must be reduced by > 30%
142
what pathways does PT assess
extrinsic & final common
143
what 2 enzyme inhibitors turn off the fibrinolytic process
1. tPAI
2. alpha 2 antiplasmin
144
how are plasmin activators used therapeutically
dissolve thrombi to restore flow
145
what does PT measure
time it takes to form a clot using tissue factor and calcium
146
which lab test monitors therapeutic response to warfarin
PT
147
normal PT
12-14 seconds
148
when will a decrease in PT be seen
Factors must be reduced by > 30% before a change in PT is observed
149
calculation that standardizes PT results
INR
150
what is INR based on
ratio between patient’s PT and the standard mean PT
151
normal INR in healthy pts
~1
152
target INR for pts on warfarin
2-3x control
153
lab that guides heparin dosing
ACT
154
normal ACT
90-120 seconds
## Footnote
Should be > 400 seconds before going on CPB
155
normal ACT
90-120 seconds
## Footnote
Should be > 400 seconds before going on CPB
156
when is ACT measured
before heparin admin, 3 minutes after it’s given, and every 30 min thereafter
157
what lab tends to be more accurate when large doses of heparin are given
ACT > PTT
158
factors that affect ACT
* hypothermia
* thrombocytopenia
* deficiency of fibrinogen
* deficiency of factor 7
* deficiency of factor 12
159
plt count that indicates inc surgical bleeding risk
< 50,000
160
plt count that indicates inc surgical bleeding risk
< 50,000
161
plt count that indicates increased spontaneous bleeding risk
<20,000
162
plt count that indicates increased spontaneous bleeding risk
<20,000
163
lab test that monitors platelet **function**
bleeding time
164
normal bleeding time value
2-10 minutes
165
what drugs prolong bleeding time
aspirin
NSAIDs
166
what does D-dimer monitor for
fibrinolysis (fibrin degradation products)
167
what does increased d-dimer indicate
fibrinolysis
if increased, likely a thrombus present
168
differential with increased D-dimer
DVT
PE
DIC
169
Provides a “real time” visual representation of disorders of coagulation & fibrinolysis
TEG
170
TEG: R time
time to begin forming clot
171
normal R time (TEG)
6-8 minutes
172
treatment for prolonged R time
(TEG)
FFP
173
TEG: K time
time until clot has achieved fixed strength
174
normal value of K time (TEG)
3-7 minutes
175
treatment for prolonged K time (TEG)
cryo
176
what is the alpha angle in a TEG result
speed of fibrin accumulation
177
treatment of increased alpha angle (TEG)
cryo
178
normal alpha angle (TEG)
50-60 degrees
179
what is maximum amplitude of TEG
highest verticle amplitude
measures clot strength
180
what is A60 on TEG
height of verticle amplitude 60 min after max amplitude
181
normal A60 value (TEG)
MA - 5
182
what does an increased A60 in TEG indicate
excess fibrinolysis
183
treatment of increased A60
TXA
Amicar
184
produces endogenous heparin
basophils, mast cells, and the liver
185
what is exogenous heparin derived from
bovine lung and pig GI mucosa
186
naturally occurring anticoagulant that circulates in plasma
antithrombin
187
pathways inhibited by heparin
intrinsic
final common
188
MOA of heparin
* binds to AT and greatly accelerates its anticoagulant ability (1000-fold)
* heparin-AT complex neutralizes thrombin & activated factors 9, 10, 11, and 12
## Footnote
also inhibits platelet function
189
MOA of heparin
* binds to AT and greatly accelerates its anticoagulant ability (1000-fold)
* heparin-AT complex neutralizes thrombin & activated factors 9, 10, 11, and 12
## Footnote
also inhibits platelet function
190
MOA of heparin
* binds to AT and greatly accelerates its anticoagulant ability (1000-fold)
* heparin-AT complex neutralizes thrombin & activated factors 9, 10, 11, and 12
## Footnote
also inhibits platelet function
191
what should be considered if heparin fails to adequately anticoagulate
AT deficiency
192
Vd of heparin
small
193
how is heparin metabolized
heparinase
194
2 pathways for heparin elimination
1. degradation by macrophages
2. renal excretion
195
is heparin safe in pregnancy
yes - does not cross placenta
196
1 unit heparin =
the volume of heparin-containing solution that prevents 1 mL of citrated sheep blood from clotting for one hour following the addition of 0.2 mL of 1:100 CaCI
197
heparin dosing. for cardiac surgery
300-400 units/kg IV
198
heparin dosing for VTE prophylaxis
5,000 U SQ BID or TID
199
heparin dosing for active VTE
5,000 U IV then infusion of ~ 1,250 U/hr to maintain aPTT 1.5 - 2.5x normal
200
heparin dosing for unstable angina & MI
5,000 U IV then infusion of 1,000 U/hr
201
aPTT that indicates therapeutic heparinization
1.5-2.5x normal
(normal = 25-35 sec)
202
Side effects of heparin
* hemorrhage
* heparin-induced thrombocytopenia (HIT)
* allergic reaction
* hypotension
* decreased antithrombin concentration
203
heparin contraindications
NSGY
HIT
regional anesthesia
204
MOA of protamine
highly alkaline, strong positive charge + negative charge of heparin = neutralization reaction that stops heparin’s anticoagulant
205
dosing protamine
1 mg protamine for every 100 U heparin predicted to be in circulation
206
how is the heparin-protamine complex cleared
Reticuloendothelial system
207
function of protamine when given alone
anticoagulant
208
3 side effects of protamine
1. hypotension
2. pulmonary HTN
3. allergic reaction
209
what causes hypotension with protamine
histamine release
## Footnote
give over > 5 min
210
what causes pulmonary HTN with protamine
thromboxane A2 and serotonin release
211
factors that increase risk of allergic reaction to protamine
* sensitization to NPH insulin
* fish allergy
* vasectomy
* multiple allergies
212
MOA of warfarin
Inhibits the enzyme vitamin K epoxide reductase complex 1 (VKOR c1)
213
factors indirectly inhibited by warfarin
214
responsible for converting inactive vitamin K to active vitamin K
vitamin K epoxide reductase complex 1 (VKOR c1)
| inhibited by warfarin
215
factors indirectly blocked by warfarin
vitamin-K dependent (2, 7, 9, 10)
proteins c and s
216
protein binding of warfarin
highly protein bound
217
how long required to achieve therapeutic concentration of warfarin
36-72 hours
218
warfarin antidote
Vitamin K and FFP
219
how to reverse warfarin for emergent or high-risk procedures
1-2 units FFP, recombinant factor 7a, or prothrombin complex concentrate
## Footnote
high risk = NSGY procedures
220
how to reverse warfarin for non-emergent minor surgical procedures
10-20 mg vitamin K
221
how is plasminogen converted to plasmin
by tPA
222
what is required for absorption of vitamin K
presence of fat and bile for absorption
223
risk factors for vitamin K deficiency
1. poor dietary intake
2. antibiotics
3. malabsorption d/t obstructive biliary tract disease
4. Hepatocellular disease
5. Neonates
224
what is phyntonadione
exogenously administered vitamin K
225
required for exogenous vitamin K admin
a functional liver
226
how long does it take for exogenous vitamin K to restore concentration of vitamin K-dependent clotting factors in blood
4-8 hours
227
phytonadione dose
10-20 mg IV, IM, PO
228
risk assoc with IV phytonadione
life threatening anaphylaxis
avoid IV or give max. 1mg/min
