Antithrombotics: Afib & Stroke Flashcards
1
Q
Which thrombus is platelet rich?
A
White thrombus (ACS, non-cardioembolic stroke)
2
Q
Which thrombus forms in the veins?
A
Red thrombus
3
Q
Which thrombus is fibrin and RBC rich?
A
Red thrombus
4
Q
Which thrombus forms in the arteries?
A
White thrombus
5
Q
Thromboembolism locations?
A
Pulmonary embolism (PE) - lungs, Cerebrovascular accident - brain, Acute MI - heart, DVT - Lower extremity
6
Q
Mediators of platelet aggregation?
A
TXA2, ADP, 5-HT
7
Q
What role does TXA2 play in aggregation?
A
Platelet activation/vasoconstriction
8
Q
What is TXA2?
A
Thromboxane A2: activated by platelets during hemostasis
9
Q
What role does ADP play in aggregation?
A
Platelet activation
10
Q
What is ADP?
A
Adenosine diphosphate: triggers binding of fibrinogen to platelet receptor GPIIb/IIIa, links platelets
11
Q
What role do 5-HT receptors play in platelet aggregation?
A
Platelet aggregation/vasoconstriction
12
Q
What are 5-HT receptors?
A
Serotonin receptors, can activate blood platelets
13
Q
Which anticoagulant medication targets TXA2?
A
Aspirin
14
Q
Which anticoagulant medication targets ADP?
A
P2Y12i’s (clopidogrel, ticagrelor)
15
Q
Which medications interact with 5-HT R’s?
A
Serotonin (SSRI’s, prozac)
*agonists that may cause bleeding !
16
Q
Targets for antiplatelet drug therapy?
A
TXA2, ADP, GPIIb/IIIa
17
Q
Will the coagulation cascade go through the final common pathway if it starts with the extrinsic or intrinsic pathway?
A
BOTH, does not matter if it starts with extrinsic or intrinsic pathway - will go through final common pathway/lead to clot formation
18
Q
What is the primary difference that can be quickly assessed/lead to certain drugs being used earlier on depending on the situation?
A
The mediated factors released in the intrinsic vs. extrinsic pathway
19
Q
Common pathway?
A
- Factor Xa is activated by binding with Ca2+ and clotting factor V (forming a prothrombinase complex)
- The prothrombinase complex (Factor Xa, Ca2+, & clotting factor V) and platelet phospholipids activate prothrombin (factor II) to become thrombin (factor IIa)
- Thrombin (factor IIa) cleaves fibrinogen (factor I) into fibrin (factor Ia)
- Thrombin cleaves stabilizing factor (XIII) into factor XIIIa
- Factor XIIIa binds with calcium & creates fibrin crosslinks to form the clot
20
Q
Intrinsic pathway?
A
- Begins when factor XII is exposed to collagen, kallikrein, and kininogen from a damaged surface and is activated to factor XIIa
- Factor XIIa activates factor XI into XIa
- With a calcium ion, factor XIa activates factor IX into IXa
- Factor IXa, factor VIIIa, and calcium form a complex to activate factor X into factor Xa
- Common pathway
*Factor VIII is found in the blood and is often activated by thrombin (factor IIa)
21
Q
Extrinsic pathway?
A
- Begins w/ injury to endothelial tissue releasing tissue factor (factor III) into the blood
- Trauma causes factor VII to become factor VIIa
- Tissue factor binds with factor VIIa and Ca2+ to activate factor X to factor Xa
- Common pathway
22
Q
Do heparin and warfarin interfere with the clotting pathway prior to or after factor Xa is formed?
A
Prior to Xa
23
Q
Can meds directly block factor Xa?
A
Yes!
24
Q
Normal activity of antithrombin?
A
Binds factors IIa, IXa, Xa, XIa, XIIa to inactivate them
*can be leveraged to our benefit w/ meds
25
Does heparin have a direct or indirect effect on thrombin?
Indirect (via antithrombin), acts like catalyst in an enzymatic reaction
26
Antithrombin sites of activity are mostly along the which part of the coagulation pathway?
Mostly along intrinsic pathway to the common pathway of coagulation cascade
27
Indications for use of unfractioned heparin (UFH)?
Ischemic heart disease (generally during PCI), During cardioversion for for A-fib, VTE prophylaxis, VTE treatment, to keep lines open for patients during surgery/dialysis, etc.
VTE = venous thromboembolism
28
Which clotting factors does UFH inhibit?
Factors X and II
29
When is UFH administered as a continuous infusion?
for ACS and warfarin bridging (VTE treatment)
30
When is UFH administered as a subcutaneous injection?
for VTE prophylaxis
31
What should be monitored with UFH therapy?
aPTT
32
Goal level aPTT with UFH?
2-2.5x control (approximately 60-80 sec)
33
Adverse effects of UFH?
Bleeding, HIT (heparin induced thrombocytopenia), Osteoporosis
34
What is Heparin induced thrombocytopenia (HIT)?
Antibody mediated adverse effect of heparin that is strongly associated with thrombosis/platelet clotting (resulting in platelet levels dropping)
35
Monitoring parameters for HIT?
-If platelets fall >50% from baseline w/ nadir (lowest count) > 20,000
-If platelets start to fall on day 5-10 of tx
-If thrombosis occurs while on heparin
-Rule out other causes of thrombocytopenia
36
What is thrombocytopenia?
Platelet deficiency in the blood
37
Treatment for HIT?
Stop heparin, treat w/ IV direct thrombin inhibitor
38
What should be avoided in HIT treatement?
*DO NOT administer platelets
*DO NOT give warfarin, or give direct oral anticoagulant (DOAC) to patients until platelets return to normal
39
Which complex acts on resting platelets in HIT?
Anti-heparin/PF4 IgG immune complex
40
When to use Low molecular weight heparin (LMWH)?
Commonly used for ACS, can be used for warfarin bridging, DVT prophylaxis
41
Types of LMWH?
Enoxaparin (Levenox), Dalteparin, Tinzaparin
42
Enoxaparin (Levenox) administered how often?
Every 12 hours if CrCl > 30
43
Which factors does LMWH act on?
Inhibit factor Xa > IIa
44
How is LWMH administered for ACS, warfarin bridging (acute VTE tx), and VTE prophylaxis?
Subcutaneous injection
45
Monitoring for LWMH?
Not routinely done, may monitor Anti-Xa level in peds or at risk pts
46
Dosing of LWMH in reduced renal function?
If CrCl <30reduce Levonox to q24hrs
If CrCl <10 or acute renal failure ---> Switch to Heparin
**Not for use in patients w/ severe renal dysfunction
47
What is considered acute renal failure?
Any change in CrCl of 0.3 or more from baseline
48
Adverse effects of LWMH?
Bleeding, HIT is extremely rare
49
How do fibrinolytics break up clots?
t-PA (alteplase) binds to fibrin in thrombus and converts plasminogen to plasmin to break up fibrin
50
When are fibrinolytics used?
Will use in ischemic stroke, might use for PE, sometimes used for ACS
51
Mortality benefit of fibrinolytics last how long?
Only 3 hours
52
Window for t-PA administration to stop progression/loss of some function?
3-4.5 hours (morbidity benefit post 3 hours, but no mortality benefit)
53
Which is the active form: plasminogen or plasmin?
Plasmin- breaks down the clot (active form)
54
Types of fibrinolytics?
t-PA/Alteplase, Reteplase, Tenectaplase
*Also streptokinase and urokinase (older agents, not used as much)
55
How is t-PA/alteplase administered?
Recombinant IV drug therapy
56
About how long does it take to form a clot in the atria?
~48 hours
57
A-fib can lead to what?
Stroke and systemic embolism (tx aims to prevent this)
58
Decide antithrombotic treatment for A-fib/flutter based on what?
Stroke risk, bleeding risk, patient characteristics/preferences
59
Guidelines recommend use of what therapy in patients w A-fib/A-flutter?
Antithrombotic therapy
60
Which antithrombotics are preferred for A-fib/A-flutter?
Anticoagulant > Antiplatelet > nothing (both better than no tx)
61
How to determine stroke risk?
CHADSVAS score
62
C in CHADSVAS score?
Congestive HF/LV dysfunction (+1 point)
63
H in CHADSVAS score?
HTN (+1 point)
64
First A in CHADSVAS score?
Age >/= 75 yrs (+ 2 points)
65
D in CHADSVAS score?
DM (+1 point)
66
First S in CHADSVAS score?
Stroke (TIE/TE) (+2 points)
67
V in CHADSVAS score?
Vascular Disease (+1 point)
68
Second A in CHADSVAS score?
Age 65-74 yrs (+1 point)
69
Second S in CHADSVAS score?
Sex - female (+1 point)
70
Risk & therapy indications w/ CHADSVAS score of 0 (male) or 1 (female)?
Low risk, no anticoagulation tx
71
Risk & therapy indications w/ CHADSVAS score of 1 (male)?
Moderate risk, oral anticoagulation should be considered
72
Risk & therapy indications w/ CHADSVAS score of 2 or greater (male and female)?
High risk, oral anticoagulation is recommended
73
Consider alternatives to anticoagulation in patients with what HAS-BLED score?
Score > or = 3
74
Choice antithrombotic in a-fib/a-flutter in patients w/ mechanical heart valve?
Warfarin
75
Choice antithrombotic in a-fib/a-flutter in patients w/ severe kidney dysfunction (CrCl < 15)?
Warfarin
76
Choice antithrombotic in a-fib/a-flutter in patients w/ CHADSVAS score of > or = 2?
Warfarin, Dabigatran, Rivaroxaban, Apixaban, Edoxaban
77
Choice antithrombotic in a-fib/a-flutter in patients w/ CHADSVAS score of 1?
Anticoagulant, Aspirin, or no antithrombotic
78
All DOACs have different doses based on what?
Indication
79
DOACs can't be used in what kind of A-fib?
Valvular A-fib
80
What class of anticoagulants are recommended over VKAs (vitamin K antagonists) in American, European, & Canadian guidelines?
DOAC's
*subject to change w/ rapid changes to literature
*except in situations where VKAs are preferred (i.e. severe renal dysfunction, mechanical heart valve, etc.)
81
Which DOAC reduces stroke better than VKA, and has an increased risk of GI bleed and MI?
Dabigatran
82
Which DOAC reduces the risk of bleeding compared to traditional therapy?
Apixaban
83
One of the major studies that concluded DOACs are recommended over Warfarin in A-fib per updated guidelines?
ENGAGE AF-TIMI 48: Edoxaban vs. Warfarin in patients w/ A-fib
84
Among patients with nonvalvular A-fib, how does edoxaban compare with warfarin in preventing stroke or systemic embolism?
No difference in DOAC vs. Warfarin when it comes to anticoagulation activity in A-fib, yet DOACs are safer when it comes to bleeding risks
85
Which is more expensive: Warfarin or Edoxaban?
Edoxaban (~$1,000/yr vs. $60/yr for Warfarin)
86
Which patient preferences may determine choice of antithrombotic therapy in A-fib/A-flutter?
Regular INR monitoring, Inconsistent diet, cost & insurance coverage, other meds (drud-drug interactions), difficulty w/ remembering doses
87
Which type of stroke accounts for 88% of strokes?
Ischemic stroke
88
What are the two types of ischemic stroke?
Cardioembolic, non-cardioembolic
89
What is an ischemic stroke?
Blood clots stop flow of blood to area of the brain
90
What is a hemorrhagic stroke?
Blood leaks into brain tissue due to rupture of weakened or diseased blood vessels
91
Goals of therapy in stroke treatment?
Reduce neurologic injury to prevent mortality & long term disability (acute ischemic stroke), and prevent reoccurrence (secondary stroke prevention)
92
Therapy administered up to 3 hours post-stroke signs and symptoms present has what benefit?
Mortality benefit
93
Therapy administered up to 4.5 hours post-stroke signs and symptoms present has what benefit?
Morbidity benefit
94
What 2 medications are used to treat acute ischemic stroke?
IV t-PA (Alteplase) and Aspirin PO
95
How long after administering t-PA should you wait before starting Aspirin tx?
Wait 24-48 hours after t-PA before giving ASA
96
Step 1 of stroke treatment protocol?
Activate stroke team
97
Step 2 of stroke treatment protocol?
Treat as early as possible (w/in 4.5 hours of sx onset)
98
Step 3 of stroke treatment protocol?
CT scan/rule out hemorrhage
99
Step 4 of stroke treatment protocol?
Meet inclusion & exclusion criteria fr t-PA
100
Step 5 of stroke treatment protocol?
Administer t-PA with 10% given as initial bolus over 1 min
101
Step 6 of stroke treatment protocol?
Avoid all antithrombotic therapy (including Aspirin) for 24 hours
102
Step 7 of stroke treatment protocol?
Monitor patient closely for BP, response, possible hemorrhage
103
Inclusion criteria for t-PA (Alteplase) use in acute ischemic stroke?
-Age 18 & up
-Clinical dx of ischemic stroke causing measurable neurological deficit
-Time of sx onset well established to be less than 4.5 hrs before treatment initiation
104
Exclusion criteria for t-PA (Alteplase) use in acute ischemic stroke?
-Active internal bleeding (ex. GI/GU bleed w/in 21 days)
-Recent use of anticoagulant (ex. Warfarin) and elevated PT (>15 sec)/INR
-SBP > 185 mmHg or DBP > 110 mmHg at time of treatment
105
Secondary stroke prevention methods?
Statins, BP reduction, Smoking cessation, Antiplatelet treatment
106
When should statins be used for secondary stroke prevention?
In patients with presumed atherosclerotic origin
107
Which statins are recommended if necessary for secondary stroke prevention?
High-intensity statins: Atorvastatin, Rosuvastatin
108
Desired BP reduction levels for secondary stroke prevention?
<140/90 mmHg
109
Which meds for BP reduction in secondary stroke prevention?
CCB/ACEi/HCTZ > BB
110
What can be used in place of antiplatelet treatment if stroke is cardioembolic (from A-fib) for prevention of secondary stroke?
Anticoagulation (DOACs or Warfarin)
111
Non-cardioembolic antiplatelet treatment for secondary stroke prevention?
Aspirin/Clopidogrel (Plavix)/Aggrenox
112
What is Aggrenox?
Aspirin plus ER dipyridamole (combo drug)
113
In what circumstances would a patient qualify for anticoagulant tx but we would refrain from giving it?
Pregnancy, elderly w/ fall risk, etc. (aspirin or maybe clopidogrel instead)
114
Heparin is helpful because…?
Can be reversed more quickly/short half-life in case of need for immediate surgery
115
Is heparin cleared renally?
No, safe for acute renal failure
116
If CrCl is <30, do you reduce the dose or frequency of Lovenox (enoxaparin)?
Reduce frequency (ex. reduce to once daily vs. twice daily)
117
What type of clots would benefit from fibrinolytics?
Will use in ischemic stroke, sometimes in PE, sometimes in ACS
118
Risk w/ finrinolytics?
Will break up any clot, may cause bleeding
119
Would fibrinolytics be used in stable DVT or stable PE?
No
120
What does the HASBLED tool measure?
Risk of bleeding if on an anticoagulant
