Antithrombotics Flashcards
1
Q
What are the 3 categories of antithrombotics?
A
Anticoagulants
Fibrinolytics
Antiplatelets
2
Q
What do anticoagulants do?
A
stop clot formation and extension (won’t break up an existing clot)
3
Q
What do Fibrinolytics do?
A
Break up existing clots
4
Q
What do antiplatelets do?
A
stop platelets
5
Q
What are the two types of thrombi?
A
White thrombus
Red Thrombus
6
Q
What are white thrombi made up of?
A
Rich in platelets
7
Q
Where do white thrombi form?
A
in the arteries
8
Q
What are red thrombi made up of?
A
Fibrin and RBC rich
9
Q
Where do red thrombi form?
A
Veins
10
Q
What are the mediators of platelet aggregation?
A
TXA2:
ADP
5-HT
11
Q
What does TXA2 do?
A
Platelet activation and vasoconstriction
12
Q
What is ADP’s role in platelet aggregation?
A
Platelet activation and aggregation
13
Q
What is 5-HT’s role in platelet aggregation?
A
Platelet aggregation and vasoconstriction
14
Q
What activates platelets (7 step process)
A
- Injury
- Collagen and vWF exposed
- Platelet adherence and activation
- Vasoconstrictors platelet recruiters and platelet activators
- Conformational change to IIb/IIIa receptor
- Binding of fibrinogen
- Aggregation and platelet plug formation
15
Q
Where in the 7 step process do anti platelets work?
A
4-vasocontrictors, platelet recruiters, and platelet activators
5-IIb/IIIa receptors
16
Q
What are the three pathways of the coagulation cascade?
A
Intrinsic pathway
Extrinsic pathway
Common pathway
17
Q
What is the intrinsic pathway activated by?
A
Exposed endothelium
18
Q
What is the extrinsic pathway activated by?
A
Tissue damage
19
Q
What contributes to the common pathway?
A
merging of the intrinsic and extrinsic pathway
20
Q
What is the final step in both extrinsic and intrinsic pathways?
A
conversion of factor X to factor Xa(activated)
21
Q
What does factor Xa do in the common pathway?
A
Converts prothrombin (Factor II) to Thrombin (with the help of other contributors)
22
Q
What does Thrombin do in the common pathway?
A
Converts Fibrinogen to fibrin
23
Q
What does fibrin form in the common pathway?
A
fibrin clot
24
Q
So if we don’t have factor ____ or factor ____ we can’t have a clot-any anticoag we have will most likely effect these two factors?
A
X and II
25
What factors does Warfarin target?
```
SNOT
Seven (7)
Nine (9)
Ten (10)
Two (2)
```
26
What tests can be used to measure clotting ability of different pathways of the cascade?
```
PT
INR
PTT
aPTT
ACT
```
27
What does PT measure?
activity of factors II, VII, IX, X (test varies per hospital)
28
What does INR measure
Same as PT II, VII, IX, X but standardized worldwide
29
What does PTT measure?
activity of factors II, V, VII, IX, X, XI, XII
30
What does ACT measure
same as PTT II, V, VII, IX, X, XI, XII but used in invasive/operative procedures
31
How do indirect thrombin inhibitors act?
by helping antithrombin de-activate clotting factors
32
What indirect thrombin inhibitors exist?
Unfractionated Heparin
LMWH-Enoxaparin
Fondaparinux
33
What is the normal active of antithrombin in the body?
Binds to factors IIa, IXa, XIa, and XIIa to inactivate them
34
What factors does unfractionated heparin bind to?
Xa and IIa (increases antithrombin by several 1,000 fold)
35
How is unfractionated heparin used?
continuous infusion for ACS and warfarin bridging (acute VTE tx)
Subcutaneous injection for VTE prophylaxis
36
How do you monitor heparin? (what is goal?)
aPTT - 2-2.5 x control approx 60-80sec
37
ADE of Unfractionated heparin
Bleeding
HIT
Osteoporosis (long term)
38
Define HIT
Antibody mediated adverse effect of heparin
| strongly associated with thrombosis
39
What are the parameters for HIT?
1. Platelets fall greater that 50% baseline with nadir greater than 20,000
2. Platelets start to fall on day 5-10 of therapy
3. Thrombosis occurs wile on heparin!!
4. Rule out other causes of thrombocytopenia (chemo,abx, critically ill)
40
What is tx for HIT?
1. Stope heparin and tx with a IV direct thrombin
2. DO NOT ADMINISTER PLATELETS
3. DO NOT give warfarin to a pt with HIT until platelets return to normal
41
Why is there a decreased platelet count with HIT?
when heparin attaches to the lately it causes the platelet to clump up and activate. This results in a lower platelet count because there appear to be less platelets.
42
Name the 1 LMWH we are supposed to know.
Enoxaparin
43
What is the MOA of Enoxaparin
Inhibits factor Xa and a little IIa
44
How is enoxaparin given?
Subcutaneously
45
What is enoxaparin used for?
ACS
Warfarin bridging (VTE tx)
and VTE prophylasix
46
What monitoring is done when giving enoxaparin?
None routinely
| but-anti-Xa can be done for those with renal dz
47
Who cannot take enoxaparin?
Pt's with severely reduced renal function (CrCl less than 20mL/min).
48
Who requires a reduced amount of enoxaparin?
Moderate renal dz
49
ADE of enoxaparin?
Bleeding
| HIT (extremely rare)
50
What characteristics do both UFH and LMWH share?
both are used for ACS, Acute VTE, and VTE prophylaxis
51
Why might you choose to use UFH over LMWH?
```
Renal dysfunction (enoxaparin accumulates)
shorter half life-so good for pt's about to have surgery
```
52
Why might you choose to use LMWH over UFH?
more predictable dose response curve
Doesn't require routine monitoring
Heparin requires continuous infusion (so if a line is placed this is ok but no line means better to give sc)
53
What is the MOA of fondaparinux?
Synthetic pentasachharide - inhibits Xa via antithrombin (no IIa inhibition)
54
How is fondaparinux administered?
sc
55
who gets fondaparinux?
Acute VTE, and VTE prophylaxis
56
What monitoring needs to be done for those on fondaparinux?
No routine tests
Not for pt's with renal dysfunction
decrease dose if CrCl less than 50, don't use if CrCl less than 30
57
ADE of fondaparinux
Bleeding
58
What can be used to reverse Heparin
Protamine
59
What can be used to reverse enoxaparin?
Protamine
60
What can be used to reverse fondaparinux
Nothing-irreversible
| give blood products
61
What are the oral direct Xa inhibitors?
(EAR)
Edoxaban
Apixaban
Rivaroxaban
62
What do all of the oral direct Xa inhibitors end with?
XAban
63
What is the MOA of rivaroxaban?
Directly inhibits Xa
64
How is rivaroxaban administered?
PO
65
What is Rivaroxaban given for?
stroke prevention for Non-valvular Afib
Tx of active VTE
Prevention of VTE after hip/knee replacement or having a VTE
66
What needs to be monitored for with Rivaroxaban?
Renal Function
Hepatic function-don't use in severe hepatic dysfunction
P-glycoprotein and CYP 3A4 drug interaction
67
What are the renal dosing guidelines for Rivaroxaban?
Reduce if Mod-Mild
| Don't use if severe
68
ADE of rivaroxaban?
Bleeding
69
What is the reversible agent for Rivaroxaban?
No reversible agent available
70
How is Apixaban administered?
PO
71
What is Apixaban used for?
Stroke Prevention for non-valvular Afib
Tx of active VTE
Prevention of VTE after hip/knee replacement or having a VTE
72
What is monitored for with Apixaban?
Hepatic and renal dysfunction-not for use in severe
| P-glycoprotein and CYP3A4 drug interactions
73
ADE apixaban
Bleeding
74
What reversible agent is available for Apixaban?
No reversible agent
75
How is Edoxaban administered?
PO
76
What is Edoxaban used for?
Stroke prevention in pts with non-valvular Afib
| Tx of active VTE
77
What is the major difference between Edoxaban and the other two oral Xa inhibitors?
Edoxaban is no approved for hip/knee replacements,
| or for prevention of additional VTE's
78
What needs to be monitored for with Edoxaban?
```
Renal function (reduce if Mild, don't use if severe or than good)-really the only time you can use this without worry is if the pt has Moderate renal dz
Hepatic function-don't use in moderate or severe
P-glycoprotein drug interactions
```
79
What is the "funny thing" about the monitoring for edoxaban?
Renal function can't be too good - don't give if greater than 95
80
ADE edoxaban?
Bleeding
81
Do any of the oral direct Xa inhibitors have a reversal agent?
no
82
What drug interaction do all of the PO direct Xa inhibitors have in common?
PGP interactions
83
Which of the PO direct Xa inhibitors have a CYP3A4 interaction?
```
Apixaban
Rivaroxaban
(Not edoxaban)
```
84
What intravenous forms of Direct Thrombin Inhibitors are there?
Argatroban
| Bivalarudin
85
What oral forms of of Direct Thrombin Inhibitors are there?
Dabigatran
86
How is Bilvalirudin administered?
IV
87
What is Bivalirudin used to tx?
ACS in pt's undergoing PCI or coronary angioplasty
| To tx confirmed or suspected HIT
88
What needs to be monitored for when using Bivalirudin?
```
Based on aPTT/ACT
Renal function (reduce if Moderate or if on hemodialysis)
```
89
ADE of Bivalirudin?
Bleeding
90
What reversal agent is available for Bivalirudin?
No reversal agent
91
How is Argatroban administered?
IV
92
What is Argatroban used for?
Tx pt's with confirmed or suspected HIT
| Those at risk of HIT undergoing PCI
93
What two IV meds are used to tx HIT?
Argatroban
| Bivalirudin
94
What is monitored for with Argatroban?
Based on aPTT/ACT
| Use caution in hepatic dysfunction
95
ADE of Argatroban?
bleeding
96
Reversal agent for Argatroban?
None
97
How is Dabigatran administered?
PO
98
What is Dabigatran used for?
Prevention of stroke and systemic embolism in pt's with non-valvular fib
VTE tx and prevention of VTE after having VTE
99
What needs to be monitored for in Dabigatran?
```
Renal function (reduce if Moderate, do not use if severe)
Hepatic function-don't use in severe dysfunction
PGP drug interactions
```
100
ADE of Dabigatran?
```
Bleeding
GI upset (d/t coating)
```
101
Reversal agent for Dabigatran?
None
102
What factors does Warfarin inhibit?
II, VII, IX, X and proteins C and S
| Also a Vitamin K antagonist
103
What is Warfarin used for?
DVT/PE tx
| Prevention of stroke in pt with Afib or heart valve replacement
104
What are the monitoring parameters for Warfarin?
INR (therapuetic dose is 2-3)
105
What are ADE of Warfarin?
Bleeding, bruising
106
What is the MOA of Warfarin?
Blocks Vit K, causing either no, or a reduced amount of vitamin K in the body. Vitamin K is required to activate 2,7,9,and10. No vitamin K precursor - no activation
107
What dose is preferable to start a new pt with Warfarin?
LOW-about 5mg/day
108
What dose would you start a pt with Warfarin who is either
Older than 75
Critically ill
has a hepatic insufficiency?
Lower 2.5mg
109
How do you adjust Warfarin dosage?
Adjust based on WEEKLY dose.
INR less than goal x 2 increase dose 10-20%
INR more than goal X2 decrease weekly dose by 10-20%
110
What is the goal for INR for pt's with
DVT/PE/aFib
Bioprosthetic valve-3 mos tx
2-3
111
What is the goal INR for pt's with
Mechanical mitral valve or any valve w/ r/f
Predisposition (leiden) who had a clot with the typical goal INR?
2.5-3.5
112
What are the problems with Warfarin?
```
Slow onset and offset (needs bridging)
dietary interactions (vit K)
Need for routine monitoring
Dose response variability
Narrow therapeutic index
Drug interaction (TONS OF THEM)
```
113
When warfarin is stopped it takes about ____ days to return to baseline.
5
114
If Warfarin is stopped and the pt is given Vit K it takes about ____ days to return to baseline
1
115
How is vitamin K administered in the event of Warfarin excess?
Oral-NOT SC or IM-does not distribute properly (NEVER GIVE VIT K SC/IM)
Can be given IV - special instructions
116
When Vitamin K is administered IV, in what way is it prepared?
IV Vit K 10mg dilutes with 50mL of NS and administered over 10-30 min. IV push will KILL THE PT!!
117
What is special about the Novel ORAL anticoagulants?
Don't require bridging!
118
What Novel oral anticoagulants exist? (2)
Direct thrombin inhibitors
| Factor Xa inhibitors
119
What are the advantages of the new oral anticoagulants?
Faster onset and offset
No routine monitoring
Few drug/food interactions
Predictable dose-response
120
What are the disadvantages of the new oral anticoagulants?
Limited clinical experience
$$$$$$
No antidote
renal excretion
121
What is the MOA of ASA?
Inhibits the COX enzyme responsible for prostaglandin and TXA2 synthesis
122
What is ASA used for?
Primary (off label) and secondary prevention of CAD
ACS tx
Chronic Stable Angina
PAD
Acute stroke/TIA tx and 2nd stroke prevention
123
What needs to be monitored for with ASA?
Bleeding
124
ADE
Bleeding
125
MOA of Clopidogrel, prasugrel, and ticagrelor
P2Y12 platelet receptor antagnoist
126
What is Clopidogrel (plavix) used for?
ACS and 2nd MI prevention
2nd stroke prevention
PAD
127
What needs to be monitored for with Clopidogrel?
CYP2C19 drug and pharm interactions
128
ADE Clopidogrel?
Bleeding
129
What is Prasugrel used for?
ACS with PCI -- if pt does not get PCI this drug is not the best choice.
130
What dosage adjustments are very important to know when prescribing Prasugrel?
Reduce dose if weight less than 60kg
Do not use in pt's with previous stroke
do not use in pt's older than 75yo, unless they have DM or previous MI
131
ADE of Prasugrel?
Bleeding
132
How is Ticagrelor used?
Tx of ACS
133
How is Ticagrelor monitored?
Hepatic function-don't use in severe
Don't use if signs of bleeding
CYP3A4 drug interaction
134
ADE ticagrelor?
bleeding
135
MOA of Dipyridamole?
ADP inhibitor which prevents platelet activation
136
How is Dipyridamole administered?
XR formulation with ASA
137
What is Dipyridamole used for?
Secondary stroke/TIA prevention
138
Who cannot take Dipyridamole?
Those with severe renal or hepatic dysfunction
139
ADE of Dipyridamole?
HA (resolves after couple days usually)
| Bleeding
140
MOA of cilostazol?
Inhibits phosophodiesterase III, preventing platelet activiation
141
What is Cilostazol used for?
PAD with intermittent claudication (VERY SPECIFIC)
142
What pt's require dose adjustments for Cilostazol
CYP 3A4 and 2C19 drug interactions
143
What needs to be monitored for with Cilostazol?
Platelets and WBC counts periodically
| Signs of bleeding
144
In what group of pt's is Cilostazol contraindicated?
Heart Failure
145
ADE of Cilostazol?
Bleeding
HA
GI upset
146
What drug is a GP IIB/IIIA inhibitor?
Eptifibatide
147
What is the MOA of GP IIB/IIIa inhibitors?
prevents platelets from cross linking with fibrinogen
148
When is Eptifibatide used?
ACS during PCI in conjunction with heparin
149
What must be monitored in use of Eptifibatide?
Renal function-decrease dose in Mild
| Do not use in end stage renal disease
150
ADE Eptifibatide
Bleeding
151
What is the MOA of Vorapaxar?
Inhibits platelet PAR-1 to prevent platelet aggregation
152
Who gets Vorapaxar?
Hx of MI
| Established PAD
153
How is Vorapaxar administered?
ONLY USED in conjunction with ASA or clopidogrel (only for really extreme circumstances)
154
What groups should not use Vorapaxar?
```
hx of stroke
TIA
intracranial hemorrhage
active bleeding
Severe hepatic dysfunction
```
155
What interactions can occur with Vorapaxar?
CYP 3A4
156
ADE Vorapaxar?
Bleeding
157
Who do Fibrinolytics work?
Convert plasminogen to plasmin to break up fibrin
158
What Medication is a Fibrinolytic?
t-PA (alteplase)
159
When is t-PA (a fibrinolytic) administered in the event of a STEMI
If no PCI available, within 30 minutes door to needle time
160
If PCI is available when must it occur in the event of a STEMI?
less than 90 minutes door to cath time
161
What 2 options exist for tx for those with NSTEMI/UA
1. Early invasive: PCI (if at high risk)
| 2. Conservative: Managed medically, see if sx resolve, undergo stress test
162
If pt undergoes Fibrinolytics for a STEMI what must this be followed with?
Enoxaparin (LMWH) for 7 days prior
163
If pt gets primary PCI what do we start and follow with?
Heparin (ITI), and Bivalirudin(DTI) infusion d/c's after PCI complete
BP IIB/IIIa inhibitor (Eptifibatide) x 12-18hrs after PCI
164
For pt's getting medical management for ACS what medication must they follow with?
Heparin continuous infusion X 48 hours
165
What medications must be given for chronic antiplatelet tx of MI
```
ASA (for everyone)
+1 other medication
Clopidogrel
or
Prasugrel
or
Tigagrelor
(ALL ADP blockers)
```
166
How is acute VTE tx?
Continous heparin infusion
| Start immediately x 5 days AND until INR 2-3 on warfarin therapy
167
What value should be monitored for a pt being tx for VTE?
Baseline aPTT
| check aPTT in 6 hours and adjust heparin based on result
168
How long must a pt who has had a first occurrence of VTE stay on warfarin?
3 months
169
How long must pt who has had a second occurrence of VTE stay on warfarin?
lifelong
170
What is the INR goal range for pt's on Warfarin
2-3 (2.5)
171
If pt is admitted how often should INR be checked?
every day
172
If pt is out-pt how often should INR be checked at first?
3-4 days
173
What options are there for prevention of VTE?
UFH
Enoxaparin
Fondaparinux
Oral XA-inhibitors - can be used for hip/knee surgery prevention
Rivaroxaban
Apixaban
Direct thrombin inhibitor
Dabigatran
174
There are two different types of stroke we covered, what are they?
Hemorrhagic
| Ischemic
175
What type of stroke can anti platelets be used to tx?
ischemic
176
What meds are used to Tx ACUTE ischemic stroke?
Intravenous tPA
| ASA (24h after IV tPA)
177
What is the stroke tx protocol? (7 steps)
1. Activate stroke team
2. Tx within 4.5h of symptom onset (no tPA if over)
3. CT scan r/o hemorrhage
4. meet inclusion criteria for tPA
5. Admin tPA 0.9 mg/kg over 1 hour w/ 10% bolus
6. Avoid all antithrombotics for 24h (including ASA)
7. Monitor closely for bleeding
178
What do exclusion factors of tPA generally include
Bleeding risk
179
What is the recommended tx for secondary stroke prevention?
ASA
Clopidogrel (if pt can't tolerate ASA)
ASA plus dipyridamole (Aggrenox)
Warfarin for pts w/ cardioembolic stroke
180
What is recommended tx for pt's with PAD?
ASA daily
Clopidogrel- for pt's who can't tolerate ASA
Cilostazol-for pt's with INTERMITTENT claudication
181
Explain CHA2DS2-VASc score
```
C-CHF (1)
H-HTN (1)
A-Age over 75 (2)
D-DM (1)
S-Stroke (2)
V-Vascular dz (1)
A-Age 65-74 (1)
S-Sex (female) (1)
Determines stroke risk
```
182
Choice of antithrombotic in afib/flutter is based on ______?
Patient's characteristics
183
What antithrombotic should a pt with a hx of a mechanical heart valve be paced on?
Warfarin
184
What antithrombotic should a pt with a hx of ACS be placed on?
Warfarin
185
What antithrombotic should a pt with a hx of Severe kidney dysfunction be put on?
Warfarin
186
If a pt has a CHA2DS2-VASc score greater than 2, what antithrombotic tx should they be on?
```
Warfarin
Dabigatran
Rivaroxaban
Apixaban
Edoxaban
```
187
If a pt has a CHA2DS2-VASc score of 1, what antithrombotic tx should they be on?
either no antithrombotic or
anticoagulant
asa
