Exam 3: Anticoagulants & Antiplatelet Drugs Flashcards
(132 cards)
1
Q
Define hemostasis:
A
Cessation of bleeding from injured vessels
2
Q
Mechanisms (3) of hemostasis:
A
Platelets
Clotting factors
Vasoconstriction
3
Q
Steps (5) of hemostasis:
A
Vasoconstriction Formation of plt plug Activation of clotting cascade Formation of fibrin clot Clot retraction/lysis
4
Q
Describe primary hemostasis:
A
Occurs immediately in response to vessel injury
Exposed subendothelial collagen attracts circulating platelets, which adhere and form plug
5
Q
Primary hemostasis is promoted by:
A
Pro-coagulants:
von Willebrand factor
Clotting factor VIII
Adenosine diphosphate
6
Q
Effect of primary hemostasis on vascular tone:
A
Causes localized vasoconstriction
7
Q
Blood cell flow patterns in the vessel:
A
Platelets (heavier) flow along the edges of the vessels d/t radial dispersion
8
Q
Activation of platelets causes (3):
A
Change in shape/formation of pseudopods
Release of thromboxane A2
Degranulation/release of biochemicals
9
Q
Connecting agents in platelet aggregation:
A
Fibrinogen
vWF
10
Q
Agents released in degranulation:
A
Serotonin + histamine Thromboxane ADP Clotting factors Va, VIIIa, IXa Platelet factor 4
11
Q
Role of serotonin + histamine in clotting:
A
Vasoconstrictors
12
Q
Role of thromboxane in clotting:
A
Vasoconstriction
Degranulation of adjacent platelets
13
Q
Role of ADP in clotting:
A
Promotes Adherence and Degranulation of Platelets (A-D-P) by causing membranes to become sticky
Sticky ADP
14
Q
Role of platelet factor 4 in clotting:
A
Heparin-neutralizing; enhances clot formation
15
Q
Factor used in the intrinsic pathway:
A
XIIa
16
Q
Factors used in the extrinsic pathway:
A
Tissue factor
Factor VIIa
17
Q
Final common pathway of the coagulation cascade:
A
Factor Xa
Prothrombin (Factor II) –> Thrombin
Fibrinogen –> Fibrin
18
Q
Describe secondary hemostasis:
A
Slower process (minutes to hours) that results in formation of fibrin clot (scab)
19
Q
Describe a fibrin clot:
A
Meshwork of protein strands that stabilize the platelet plug and trap cells
20
Q
At baseline, the coagulation/anticoagulation balance is:
A
Leaning more towards coagulation
21
Q
Natural anticoagulants (5):
A
Prostacyclin (PCI2) Antithrombin III Hepatin Protein C Protein S
22
Q
Events that happen when clot “retracts”:
A
Fibrin strands shorten
Platelets use contractile proteins
Protein-free serum squeezed from cells
23
Q
Clot lysis mediated by:
A
Plasmin
24
Q
Role of plasmin:
A
To split fibrin and fibrinogen into fibrin degradation products (FDPs)
25
Five oral antiplatelets:
```
Aspirin
Ticlopidine
Clopidogrel (Plavix)
Prasugrel
Ticagrelor (Brilinta)
```
26
Three IV antiplatelets:
Abciximab
Eptifibatide
Tirofiban
27
MoA of aspirin:
COX inhibitor; irreversibly prevents the production of thromboxane A2
28
Indications for aspirin:
Prevention of recurrent ischemic events (MI, stroke, PAD)
29
Dosage of aspirin:
81-325mg qday
30
Precautions with aspirin:
Children (Reye's syndrome)
Pregnancy
Asthmatics (↑ leukotrienes and bronchoconstriction)
31
Cardiovascular drug interactions with aspirin:
Blunts effects of ACEIs, β-blockers, and diruetics
Prostaglandin inhibition blocks the vasodilatory effects
32
Tx of bleeding when on aspirin:
Plt transfusion
33
MoA of ticlopidine:
Blocks ADP receptor on platelet, inhibits fibrinogen binding
34
Indications for ticlopidine:
Prevention of recurrent ischemic events (esp. in ASA intolerance)
35
S/E of ticlopidine:
Neutropenia
Thrombotic thrombocytopenic purpura
GI upset
Teratogenesis
36
MoA of clopidogrel:
Irreversibly blocks ADP receptor on platelet and inhibits fibrinogen binding
37
Indications for clopidogrel:
Prevention of recurrent ischemic events: stroke, recent ACS, post-PCI
38
Clopidogrel vs. ASA for monotherapy:
Clopidogrel more effective but more costly
39
Dosage of clopidogrel:
Loading dose 300-600mg
| Daily dose 75mg
40
Precautions with clopidogrel:
Metabolized by CYP2C19 - genetically poor metabolizers may need more
CYP450 inhibitor
Adjust dose for renal/hepatic
Use with other anticoags
41
Tx of bleeding on clopidogrel:
D/c drug
| Plt transfusion
42
Class of drug for clopidogrel:
Thienopyridine
43
Class of drug for prasugrel:
Thienopyridine
44
Prasugrel vs. clopidogrel:
Prasugrel more effective but also more fatal bleeding events
Works in non-responders to clopidogrel
45
Dosing of prasugrel:
10mg qday
46
Precautions/contraindications with prasugrel:
Active bleeding
Previous stroke/TIA, underweight, elderly: consider 5mg/day instead
Do not use pre-cath!
47
MoA of ticagrelor:
Allosteric ADP antagonist
48
Ticagrelor vs. clopidogrel:
Ticagrelor has better death reduction post-MI than clopidogrel when it comes to vascular causes (MI/stroke)
Ticagrelor has higher rate of bleeding and higher rate fatal brain bleeding
49
Indications for ticagrelor:
Prevention of recurrent ischemic events after MI
50
Dosage for ticagrelor:
Loading: 180mg
90mg BID
Always given w/ ASA unless contraindicated
51
Precautions for ticagrelor:
Hepatic dysfunction
ASA > 100mg/day
5 days pre-op
Compliance (BID)
52
Contraindications for ticagrelor:
Active bleeding
| Hx of intracranial hemorrhage
53
MoA of GPIIb/IIIa inhibitors:
Prevent fibrinogen binding to GPIIb/IIIa receptors by inhibiting them
54
Indications for GPIIb/IIIa inhibitors:
```
ACS
PCI (intra- and post-procedure)
```
55
Examples of GPIIb/IIIa inhibitors:
Abciximab
Eptifabatide (Integrillin)
Tirofiban
56
Indications and notables for abciximab:
Planned PCI
| Most expensive, longest lasting
57
Dosing for eptifibatide:
If Cr is < 2: 2 mcg/kg/min up to 72 hrs
| If Cr is > 2: 1 mcg/kg/min up to 72 hrs
58
Tx for bleeding on abciximab:
Plt transfusion
59
Tx for bleeding on eptifibatide and tirofiban:
D/c drug and wait/transfuse
60
Pre-op interruption of anti-platelet therapy:
7-10 days pre-op
| Pts at high cardiac risk continue ASA, clopidogrel stop 5 days prior
61
Post-op resumption of anti-platelet therapy:
24 hrs/next AM post-op (as long as hemostasis was achieved)
62
MoA of heparin:
Activates antithrombin III, which increases inhibition of thrombin (IIa) and factor Xa by 1000x
63
Indications for heparin:
DVT prophylaxis/tx
PE tx
ACS
Warfarin bridge (or just contraindicated)
64
Dosing for heparin:
DVT: 5000 units q8hr (q12hr in neuro)
| IV infusion - weight-based and titrated based on aPTT
65
Drawbacks of heparin:
Variable effect
| Unable to inhibit clot-bound thrombin (cannot break down existing clots)
66
Tx of bleeding on heparin:
Stop the heparin - look for hidden sources
| Reverse with protamine 1mg/100U heparin (or just give 50mg bolus)
67
Adverse effects of heparin:
Benign thrombocytopenia
| HIT
68
Type I HIT:
Benign; less common
Mild drop in plts within 4 days of starting tx
Not progressive
69
Type II HIT:
Typical onset, following heparin exposure
Reduction in plts to < 150k or by 50%
5-14 days post-exposure
70
Incidence of HIT:
2-5%; surgical > medical > obstetric
71
Onset of HIT:
Typical: 5-14 days
Delayed (rare): 2-6 weeks
Rapid onset: 25%, from hours to days (usually with additional heparin exposure within last 100 days)
72
Types of HITT:
Venous (4x as common)
| Arterial
73
Sequelae of venous HITT:
DVT
PE
Venous limb gangrene
Dural sinus thrombosis
74
Sequelae of arterial HITT:
```
Stroke
Limb ischemia/skin necrosis
MI
Mesenteric ischemia
Adrenal/renal/spinal artery infarcts
```
75
Mortality rate of HITT:
25-30% mortality
| 25% amputation rate
76
Lab testing for HIT (2):
ELISA - measures titer of IgG antibody to heparin (in-house)
| C-serotonin release assay - detects plt activation (send-out test - confirmatory)
77
Tx of HIT:
Stop all thrombocytopenia-inducing drugs
| Stop hepatin and start argatroban
78
MoA of enoxaparin:
Binds with antithrombin III and inhibits Xa
79
Indications of enoxaparin:
DVT prophylaxis
ACS
VTE tx
80
Dosage of enoxaparin:
DVT proph: 40mg q24h
THR/TKR: 30mg q12h
DVT tx: 1-1.5 mg/kg qday
ACS: 1 mg/kg qday
81
Lab monitoring for enoxaparin:
Not routinely monitored; anti-Xa levels if needed
82
Precautions for enoxaparin:
Pregnancy (monitor antiXa)
Obese (weight-based dosing)
Severe renal insufficiency (if CrCl < 30ml/min reduce dose 50%)
Avoid in spine surgury/epidural catheters
83
Tx of bleeding on enoxaparin:
Protamine reverses 60%
84
MoA of fondaparinux:
Synthetic Xa inhibitor; binds with antithrombin III to potentiate Xa inhibition 300x
*No* effect on IIa (thrombin)
85
Indications for fondaparinux:
ACS
DVT proph
DVT/PE tx
Very expensive!
86
Dosing of fondaparinux:
Proph: 7.5mg qday
| VTE/>100kg: 10mg qday
87
Contraindications of fondaparinux:
CrCl < 30ml/min
| Spinal anesthesia/lumbar puncture
88
Tx of bleeding on fondaparinux:
No reversal, FFP ineffective
| D/c drug, supportive care
89
IV direct thrombin (IIa) inhibitors:
```
Hirudin
Lepirudin
Desirudin
Hirulog
Argatroban
Bivalirudin
```
90
Indications for direct IIa inhibitors:
HIT (Argatroban, Lepirudin)
| PCI (Bivalirudin)
91
Special consideration with lepirudin and desirudin:
Can only use once d/t anaphylaxis risk
92
Tx of bleeding on direct IIa inhibitor:
Stop infusion
| Factor VII/FFP/cryo
93
MoA of warfarin:
Interferes with the production of Vit K-dependent clotting factors (II, VII, IX, X)
Interferes with natural anticoagulants Protein C and Protein S
94
Indications for warfarin:
Prevention of DVT/Afib/heart valve thrombosis
| Long-term VTE
95
Dosage of warfarin:
Start with 5-10mg/day
| Base adjustments on PT/INR
96
Therapeutic INR goal for warfarin:
Normal: 2.0 - 3.0
High risk: 2.5 - 3.0
High risk = mechanical valves, prev. thrombus, anti-phospholipid syndrome
97
Initiation of warfarin:
Overlap with heparin/LWMH for 1-2 days
98
Duration of warfarin therapy:
3 months for uncomplicated DVT/PE
99
Toxicity from warfarin:
Bleeding
Birth defects
Cutaneous necrosis
100
Drugs that increase the effect of warfarin:
Amiodarone
Cimetidine
Acetaminophen
Phenylbutazone
101
Drugs that decrease the effect of warfarin:
```
Sucralfate
Cholestyramine
Spironolactone
Barbiturates
Foods containing Vit. K
```
102
Dosing adjustments for warfarin:
Subtherapeutic INR: same dose, recheck 1-2 weeks
| Supratherapeutic INR: hold next dose, recheck within 1 week
103
Tx of bleeding on warfarin:
```
Vitamin K (oral/IV)
FFP
```
104
INR of FFP:
1.5
105
Pre-op hold time for warfarin:
Normal: 5 days
| High-risk: bridge with heparin until 4-6 hrs pre-op
106
Post-op resumption of warfarin:
12-24 hours
107
MoA of dabigatran/Pradaxa:
Direct thrombin/IIa inhibitor
108
Indications for dabigatran/Pradaxa:
Prevention of stroke in non-valvular afib and tx of DVT/PE
109
Dosage of dabigatran/Pradaxa:
110 or 150mg BID
| Lower dose for bleeding risk, elderly, renal impairment
110
Advantages of dabigatran/Pradaxa:
```
No monitoring
Predictable PK
Less diet/drug influence
Rapid time to peak (1hr)
Short t1/2 (12-14 hrs)
```
111
Disadvantages of dabigatran/Pradaxa:
```
High cost
BID dosing
No antidote - yet
No lab assay
No long-term data
```
112
MoA of rivaroxaban/Xarelto:
Direct factor Xa inhibitor
rivaro XA BAN
113
Indications for rivaroxaban/Xarelto:
Stroke/embolus prevention in non-valvular afib
DVT prevention post-knee/hip replacement
Tx of PE/DVT
114
Dosage of rivaroxaban/Xarelto:
20mg qday
115
Warfarin vs. rivaroxaban/Xarelto:
Rivaroxaban "non-inferior" to warfarin with less risk of fatal/intracranial bleeding
116
Advantages of rivaroxaban/Xarelto:
No monitoring needed
Predictable PK
Less diet/drug influence
Daily dosing
117
Time to peak action and half-life of rivaroxaban/Xarelto:
Peak: 2.5-4 hrs
| t/12: 7-11 hrs
118
Disadvantages of rivaroxaban/Xarelto:
High cost
No antidote - yet
No lab assay
No long term data
119
MoA of apixaban/Eliquis:
Direct factor Xa inhibitor
api XA BAN
120
Indications for apixaban/Eliquis:
Stroke/emboli prevention in non-valvular afib
DVT prevention post-hip/knee replacement
Tx of DVT/PE
121
Dosage of apixaban/Eliquis:
5mg BID
122
ASA and warfarin vs. apixaban/Eliquis:
Apixaban clearly better than ASA for pts who cannot take warfarin
Apixaban superior to warfarin with less bleeding risk
123
Advantages of apixaban/Eliquis:
No routine monitoring
Predictable PK
Less diet/drug influence
124
Peak time and half-life of apixaban/Eliquis:
Time to peak: 3 hrs
| t1/2: 12 hrs
125
Disadvantages of apixaban/Eliquis:
```
High cost
BID dosing
Reversed with expensive prothrombin complex concentrate
No lab assay
No long term data
```
126
MoA of fibrinolytics:
Plasminogen activators convert plasminogen to plasmin, which causes fibrinolysis
127
Fibrinolytic agents:
```
Streptokinase
Urokinase
tPA
Recombinant tPA
Tenecteplase/TNKase
```
128
Indications for fibrinolytics:
Acute STEMI
Acute stroke (within 6 hrs of symptom onset)
CVC declotting (urokinase)
PE (urokinase)
129
Dosing of recombinant tPA:
10 units over 2 min; repeat in 30 min
130
Dosing of TNKase
30-50 mg (weight based) single bolus over 5 sec
131
Absolute contraindications for fibrinolytics:
```
Previous hemorrhagic stroke
Ischemic stroke within 3 mo
Intracranial neoplasm
Active internal bleeding
Aortic dissection
Closed head/face trauma within 3 mo
```
132
Relative contradindications for fibrinolytics:
Uncontrolled severe HTN (BP > 180/110) at presentation or in hx
INR > 2.5 on anticoags
Bleeding d/o
Non-compressible vascular puncture
Recent trauma (2-4 wks) or surgery (< 3 weeks) or internal bleeding (2-4 wks)
PUD
Pregnancy
Streptokinase - allergy or prior exposure
