Hemostasis 1.c.7 Flashcards
(145 cards)
1
Q
what is the definition of hemostasis
A
keeping the blood within the fluidic state within the confines of the vascular system
2
Q
what is in the plasma layer
A
water
proteins
clotting factors
gamma globulins
3
Q
what is in the Buffy coat
A
WBC
platelets
4
Q
what is in the RBC layer
A
O2 carrying capacity
5
Q
within the vascular system, there can be endothelial damage. What is the effects of endothelial damage?
A
- activation of platelets
- activation of plasma coagulation
- release of inhibitors
- initiation of fibrinolysis
6
Q
what is the name of the place where the two platelets come together
A
the IIB3AC receptor site
7
Q
Platelets is a ____ shape and is approx _____ microns in diameter
A
discoid shape and about 2-4 microns in diameter
8
Q
Approximately 1/3 of platelets is sequestered in the
A
spleen
9
Q
what do platelets act as
A
early responders to vascular damage
10
Q
what is the “mothership” of platelet formation?
A
megakaryocytes, which is a large precursor cell with multiple nuclei
11
Q
where are megakaryocytes normally present
A
only in bone marrow
12
Q
what is the large precursor cell that has multiple nuclei that creates platelet?
A
megakaryocytes
13
Q
how do platelets come from megakaryocytes
A
- platelets bud from cell cytoplasm
- squeeze through the marrow sinusoids into peripheral circulation
14
Q
all coagulation factors are synthesized by the liver except for
A
portion of Factor VIII (endothelium and megakaryocytes)
15
Q
Roman numeral designation except for
A
high molecular weight kininogen (HMWK)
&
pre-kalekron (PK)
16
Q
Coagulation factors function as
A
- cofactors (V and VIII)
- enzymes (active form)
- substrate (fibrinogen or factor I)
17
Q
end result of coagulation factors interaction leads to
A
fibrin formation = solid clot
18
Q
what is the “fast pathway of clotting”
A
the extrinsic pathway
19
Q
what is an example of when the extrinsic “fast pathway” is activated
A
- make an incision and shoving things up there to find a vein
- incision in chest
20
Q
how does temperature effect coagulation
A
heat it up = make it go faster
cool it down = flow it down
21
Q
“long pathway of clotting” occurs when
A
due to bypass or foreign surfaces
22
Q
___ ____ _____ is what leads to coagulation
A
free floating thrombin
23
Q
what is the 1st largest protein in the body
A
albumin
24
Q
what is the 2nd largest protein in the body
A
fibrinogen
25
what is the 3rd largest protein in the body
gamma globulins
26
Free floating thrombin regulates what coagulation reactions
factors V and VIII
| factors XI
27
what turns fibrinogen into fibrin
thrombin
28
when you hear John Hageman, what should come to mind?
factor XII
| contact/activating factor
29
what is the physiological activator of normal hemostasis?
- Tissue factor-FVIIa complex
| - the fast pathway
30
in normal hemostasis and at the molecular level, where does the interaction of coagulation factors take place?
on the surface of activated platelets
31
what is the definition of fibrinogen
break up of a clot
32
what's a D-dimer?
when you got a clot, plasminogen breaks it up into little split products
33
If you have D-dimers, what does that mean
you have activated plasminogen which you NEVER WANT TO HAVE ON BYPASS
34
clot formation come from
coagulation elements
| high suctioning
35
protein C/S in presence of thrombin forms
activated protein C (APC)
36
what does APC do
inactivate factors Va and VIIIa
| inhibits activation of factors X and II
37
what is required to synthesis for liver?
vitamin K required
38
____ _ is a major physiological inhibitor of coagulation
protein C
39
____ _ is a cofactor for Protein C
protein S
40
how often is protein C/S deficiency seen in the general population?
2-3%
41
what are some clinical manifestations of protein C/S deficiency?
- DVT
- PE
- homozygous protein C deficiency-neonatal purpura fulminans
- warfarin-induced skin necrosis following warfarin initiation in Protein C deficiency
42
what does ATIII inhibit?
thrombin, 9, 10, 11, clotting factors
43
where do you get heparin in the body
mast cells in lung
| vonkufer in the liver
44
what is AntithrombinIII synthesized by
liver and endothelial cells
45
what can increase the activity of antithrombinIII by several thousand fold?
heparin
46
when does ATIII deficiency appear and what is it an increased risk for
onset usually appears in young adulthood
| -increased risk of venous thrombosis
47
acquired ATIII deficiency can be seen if you have these characteristics....
```
acute thrombosis
DIC (disseminated intravascular coagulation)
liver disease
nephrotic syndrome
oral contraceptive use
```
48
where does heparin work?
where AT3 is
49
where does AT3 work?
```
thrombin (IIa)
Xa
IXa
XIa
XIIa
```
50
why do we not want to activate plasminogen
can lead to bradykinin
51
what is kinin mechanism involved in
inflammatory response and wound healing
52
what are some things bradykinin does? (6)
- increase vascular permeability
- vasodilation
- smooth muscle contraction
- inflammation, phagocytosis
- pain
- tissue repair
53
what does complement destroy?
collateral damage
| destroys good and bad tissue in its effort to destroy whatever made it mad
54
why do you zbuff
removing complement components
55
what can activate complement? (4)
- foreign substances such as bacteria and viruses
- components of the cardiopulmonary bypass system
- materials used in the collection and processing of autologous blood
- damage red blood cells: blood recovered from the operative site for auto transfusion
56
activation of complement results in
- macromolecular attack complex
| - cell destruction and inflammatory response
57
classical pathway fro complement
```
antigen -Ig complex
to
formation of C3 convertase
to
MAC (membrane attack complex)
```
58
alternative pathway for complement
```
pathogen surface antigen
to
formation of C3 convertase
to
peptides to increase inflammation and increase chemotasix
```
59
Together with activating plasminogen, bradykinin and all that leads toooooo
systemic inflammatory response
60
without fixing a systemic inflammatory response, can lead to
inhibit organ perfusion and multi system failure
61
when does SIRS occur
- overhwhelming sepsis
- severe trauma
- burns
- CPB
62
SIRS results in a whole body or systemic inflammatory response with disorders of
microcirculation and organ perfusion
63
SIRS leads to activation of cellular and humoral pathways such as (3)
- plasma coagulation/fibrinolysis
- complement activation and kinin generation
- activation of platelets and leukocytes
64
cooling has a big effect on anticoagulation because
it is an enzymatic process and if you cool it down, you slow it down
65
Contact activation occurs throughout all of CPB because
all foreign surfaces when inserting cannula and running blood through circuit
66
kinin generation activates
complement and antiforeign response
67
CPB effects on hemostasis (9)
- hemodilution
- hypothermia
- factor VII/tissue factor activation
- contact activation (XII)
- kinin generation
- activation of complement and systemic inflammatory response
- shear stress (platelet activation)
- fibrinolysis
- anticoagulation/reversal
68
do we care about factor XII
YES
69
factor 12 activates factors
5, 8, 11
70
goals for anticoagulation
- prevent thrombus formation
- preserve patient's hemostatic elements
- prevents SIR (systemic inflammatory response)
71
what are some anticoagulant/antithrombotic agents (5)
```
heparin
direct thrombin inhibitors
oral anticoagulants
platelet inhibitors
thrombolytics
```
72
characteristics of unfractionated heparin (UHF(
- heterogeneous substance (get it in different places in nature)
- mw: 5,000 to 30,000
- source: pig guts
- half life: 45-60 minutes
- bi phasic elimination
73
heparin + _____ is required for anticoagulant action
antithrombin III
74
what does UFH inhibit?
free thrombin and other activated coagulation proteins
75
after 7-10 minutes, how much of heparin has been eliminated?
1/3 of heparin is not available for AT3
76
for unfractionated heparin, what is the mechanism of action?
- enhances the inhibition by AT3 of thrombin(IIa) and other serine proteases
- heparin finds an ATIII and hits it and makes conformational changes on the receptor site on molecule so it can now bind and hold onto thrombin
77
how do you neutralize heparin?
by protamine sulfate
- protamine is administered, grabs the heparin complex
- AT3 can no longer make the conformational changes it needs to hold to thrombin
78
uses of UFH (9)
- cardiac surgery
- ECMO
- VADS
- cardiac Cath lab
- IR
- Dialysis
- Therapeutic
- Prophylactic
- prevent arterial and venous lines from clotting
79
what is important for anticoagulation regarding heparin?
provide sufficient drug to achieve anticoagulant and antithrombotic effect
-base on: size, sex, adult vs peds
80
what are the clinical laboratory test that can be done to monitor UFH?
- activated partial thromboplastin time (APTT): functional/qualitative, assess inhibition o plasma coagulation by heparin
- anti-Xa assay: quantitative, not amenable to POC setting
81
what are the point of care test that can be done to monitor UFH?
- activated clotting time (ACT) test: whole blood, functional, assesses global status of pt's blood coagulation
- protamine titration: whole blood, quantitative, 1:1 ratio heparin to protamine
82
low molecular weight heparin characteristics
- half life: 3-5 hrs
- inhibits activated factor X (Xa)
- incomplete reversal by protamine
- risk of bleeding is less with LMWH
- risk of HIT may be lower
83
LMWH uses
prevention&treatment of DVT and PE
- unstable angina
- myocardial infarction
- prophylaxis in hip and knee surgery
- interventional cardiology
84
why is LMWH not appropriate for CPB
- little to no anti-thrombin effect
- not reversed with protamine
- longer half life
85
Low weight molecular heparin is only monitored in limited clinical conditions. What conditions are they?
- renal insufficiency
- pts who receive LMWH over extended periods to time such as pt with cancer or who can't take warfarin
- morbid obesity/very low body weight
- very elderly, newborns, and young children
86
with LMWH, when is maximum plasma concentration reached?
1-5 hrs post injection
87
does ACT work with LMWH
no, does not reliably reflect level of anticoagulation
88
when monitoring LMWH, what factor inhibition is measured?
Xa inhibition measured
89
what is a common type of LMWH that we will use in cardiology?
Lovenox
| Enoxaparin
90
```
Lovenox
half life:
route of admin:
antidote:
indication:
effect on ACT:
```
LOVENOX
half life: 4.3 hrs
route of administration: IV or sub Q
antidote: protamine a 30% neutralization
indication: prophylaxis & treatment of VTE (hip/knee replacement, restricted mobility, unstable angina and non Q-wave MI)
effect on ACT: minimal to none
91
What is an alternative to heparin used in cardiopulmonary bypass?
direct thrombin inhibitors
92
what is Hirudo medicinal?
- antithrombotic properties of leech saliva described in 1884
- 1980s: leeches used for microvascular/reattachment surgery
- 2004: FDA cleared medical device for restoration of blood flow in cosmetic and reconstructive surgery
93
what do direct thrombin inhibitors, inhibit?
free and clot-bound thrombin
94
unlike heparin, what is not required for anticoagulant actions with direct thrombin inhibitors?
AT3
95
what are some clinical uses for Direct Thrombin Inhibitors?
- cardiac Cath lab during PTCA for replacement for heparin, usually given w platelet inhibitor
- given to its who cannot receive heparin due to antibodies against heparin (HIT)
96
what are the cons of direct thrombin inhibitors?
- no reversal agent
| - high cost relative to heparin
97
what are the direct thrombin inhibitors that are commonly used?
- Angiomax Bivalirudin (synthetic)
- Argatroban Novastan (small molecule, reversible synthetic)
- Refludan Lepirudin
98
```
Angiomax Bivalirudin
admin:
clinical indications:
effect on ACT:
monitoring:
```
admin: IV, half life 36 min, cleared by kidney
clinical indications: PTCA with aspirin or other platelet inhibitor HIT
effect on ACT: prolongs
monitoring: ACT/APTT Ecarin clotting time
99
Argatroban Novastan
admin: IV, half life 24 min, metabolized by liver
clinical indications: HIT
effect on ACT: prolongs
monitoring: ACT/APTT Ecarin clotting time
100
what are some oral anticoagulants used?
warfarin (Coumadin)
dabigitran (Pradaxa)
rivaroxaban (Xarelto)
apixaban
101
which anti coagulant was first used as rat poison
warfarin
102
warfarin is the drug with the highest potential for (2)
- clinically significant interactions with other drugs
| - changes in lifestyle and dietary habits
103
what is the drug that is the most frequently associated with drug related hospitalization due to bleeding or thrombotic complications
warfarin
104
how does warfarin work?
- absorbed from the GI tract and binds to ALBUMIN
- in the liver, inhibits the enzyme required for vitamin K to carboxylate the glutamic residues of several coagulation proteins
105
warfarin results in decreased levels of
- 2, 7, 9, 10
| - Protein C and Protein S
106
how long is the onset of action following ingestion of Warfarin
8-12 hrs
107
full anticoagulation of warfarin occurs ____ days following initiation
4-5 days
108
clinical indications for warfarin
- venous and arterial thrombosis
- prophylaxis in patients at risk of VTE
- prevention of thrombosis in its with fib, prosthetic heart valves, following ortho surgery
- low dose: its with indwelling catheters for extended periods of time
109
monitoring warfarin using PT/INR
- 2.0 to 3.0 for all
| - 2.5 to 3.5 in mechanical heart valves and cariogenic emboli
110
contraindications for Warfarin
- risk of hemorrhage is greater than benefits
- pregnant/nursing moms
- pre-existing hemorrhagic tendencies or blood dyscrasias
- traumatic surgery with large open areas
- recent or contemplated surgery of CNS or eyes
- lumbar puncture/any proceed with potential for uncontrollable bleeding
111
risk of non-compliance for Warfarin
- senility
- alcoholism
- mental impairemnt/lack of patient cooperation
112
when you measure PT, what is it looking at?
extrinsic pathway (factor 7)
113
when measuring PTT, what is it looking at?
12, 11, 9, 8, 10
114
INR stands for
international normalized ratios
115
new oral anticoagulants (3)
- dabigitran etexilate (Pradaxa)
- rivaroxaban (Xarelto)
- apixaban (Eliquis)
116
what does Pradaxa inhibit and what does it reduce?
- direct thrombin inhibitor
| - reduce the risk of stroke and blood clots in its with AF, not caused by a heart valve problem
117
what does Xarelto inhibit and what does it reduce?
- anti-Xa inhibitor
- reduces the risk of stroke and blood clots in pts with AF not caused by a heart valve problem
- reduce the risk of forming a blood clot in the legs and lungs of people who have just had knee or hip replacement
118
what does Xarelto treat?
DVT and PE
119
what does Eliquis inhibit and what does it reduce?
- Anti-Xa inhibitor
| - reduce the risk of stroke and blood clots in its with AF not caused by a heart valve problem
120
what is the difference between Xarelto and Eliquis?
Xarelto has a broader indication
Eliquis is very narrow and specific
121
Which new oral anticoagulants deals with AF
Pradaxa and Eliquis
122
Many people coming into surgery are going to be on
platelet inhibitor
123
_____ has to be available at 2b3 receptor site for platelets to stay together
Fibrinogen
124
what are two important platelet inhibitors?
aspirin and plavix
125
aspirin characteristics
```
MOA: cycle-oxygenase inhibition
half life: 2-3 hrs
length of effect: permanent
Admin Route: oral
effect on ACT: none
```
126
plavix characteristics
```
MOA: ADP inhibition
half life: 8 hrs
length of effect: permanent
admin route: oral
effect on ACT: none
```
127
when do you stop plavix if you are going to have surgery?
7-10 days before surgery
128
Thombolytic agents can be thought of as......
THE CLOT BUSTERS!!!
129
when you see a word ending in -ase, that means
to break up a clot
130
does heparin break up clots?
NO
| heparin does not stop clots, it slows it down
131
what is a major complication with thrombolytic agents?
bleeding
| especially intracranial
132
what are the thombolytic agents? (3)
streptokinase
urokinase
tissue plasminogen activator (TPA)
133
Streptokinase characteristics (3)
- derived from group C, b-hemolytic streptococci
- not fibrin specific
- antigenicity makes retreatment difficult
134
urokinase (Abbokinase) characteristics
- derived from cultured human cells (renal)
| - not Fibrin specific
135
Tissue Plasminogen Activator (TPA) characteristics (3)
- recombinant from human cells
- fibrin specific
- alteplase, Reteplase (rPA), tenecteplase
136
what are the antifibrinolytic agents
EACA (Amicar)
tranexamic acid (Cyclokapron)
Aptoinin (trasylol)
137
what is important to remember about antifibrinolytic agents?
inhibits plasminogen
138
Epsilon Amino Caproic Acid (Amicar) characteristics
inhibits activators of plasminogen
139
Tranexamic acid (cyclokapron)
inhibits activation of plasminogen
140
aprotinin (trasylol)
- serine protease inhibitor
- inhibits factor XIIa, kvllikrein, plasmin generator by TPA
- inhibits systemic inflammatory response
- no longer on market
141
what do you give when a pt won't stop bleeding
Recombinant Factor VIIa
- novoSeven
- powerful drug to clot everything off
142
indications for use for Recombinant Factor VIIa NovoSeven
- hemophilia A and B patients who have developed antibodies to Factor VIII/IX
- treatment of bleeding episodes in FVII deficiency
- prevention of bleeding in surgical procedures for both inhibitor pts and FVII-deficient pts
- treament of acquired hemophilia
143
why would someone have a factor VII deficiency?
because of Warfarin
144
off label use of Recombinant factor VIIa NovoSeven
- liver transplantation
- acute intra-cerebral hemorrhage
- trauma
- rescue intervention for intractable bleeding where other measures have failed
145
what is a risk for using recombinant factor VIIa NovoSeven?
risk of DIC and thromboembolic events
