Therapy of Venous Thromboembolism Flashcards
1
Q
Venous thromboembolism (VTE) results from:
A
Clot formation within the venous circulation
2
Q
Venous thromboembolism (VTE) is manifested as:
A
1) Deep vein thrombosis (DVT)
2) Pulmonary embolism (PE)
3
Q
Pharmacologic prevention significantly reduces the risk of VTE following:
A
1) Hip and knee replacement
2) Hip fracture repair
3) Major general surgery
4) Myocardial infarction
5) Ischemic stroke
4
Q
Hospitalized and acutely ill medical patients at high-VTE-risk and low-bleeding-risk should receive pharmacologic prophylaxis with __, __, or __ during hospitalization or until fully ambulatory
A
1) Low dose unfractionated heparin (UFH)
2) Low molecular weight heparin (LMWH)
3) Fondaparinux
5
Q
Routine pharmacologic prophylaxis is NOT indicated in which patients?
A
Low-VTE-risk medical patients
6
Q
How should you prevent VTE following non-orthopedic surgery?
A
1) Low dose UFH
2) LMWH
7
Q
How should you prevent VTE following following high risk orthopedic surgery (such as joint replacement surgery)?
A
1) Aspirin
2) Adjusted-dose warfarin
3) UFH
4) LMWH
5) Fondaparinux
6) Dabigatran
7) Apixaban
8) Rivaroxaban
8
Q
How long should patients take VTE prophylactics following high risk orthopedic surgery (such as joint replacement surgery)?
A
At least 10 days post-surgery
9
Q
What is the mainstay of VTE
(DVT & PE) treatment?
A
Anticoagulation therapy (Rapid-acting)
10
Q
We should establish an accurate VTE diagnosis in order to avoid:
A
Bleeding
11
Q
Traditionally, specific VTE therapy is started with:
A
LMWH or UFH overlapped with warfarin for 5 days, then the patient is maintained on warfarin
12
Q
The appropriate initial duration of therapy to effectively treat an acute first episode of VTE for all patients is:
A
3 months
13
Q
Which factors determine extending post-VTE anticoagulation therapy beyond 3 months?
A
1) Circumstances surrounding the initial thromboembolic event
2) Presence of ongoing thromboembolic risk factors
3) Bleeding risk
4) Patient preference
14
Q
What are some clinically important bleeding risk factors?
A
1) Age more than 75 years
2) Previous non-cardioembolic stroke
3) History of GI bleeding
4) Renal or hepatic impairment
5) Anemia
6) Thrombocytopenia
7) Concurrent antiplatelet administration
8) Noncompliance
9) Poor anticoagulant control (for patients on warfarin)
10) Serious acute or chronic illness
11) The presence of structural lesions (tumor, recent surgery) that could bleed
15
Q
How may Unfractionated Heparin (UFH) be given?
A
1) Subcutaneous injection
2) Continuous IV infusion
16
Q
Response to UFH is:
A
Highly variable
17
Q
UFH dose should be adjusted based on:
A
Activated partial thromboplastin time (aPTT)
18
Q
Both __ and __ produce similar clinical outcomes.
A
Weight-based and Fixed-UFH-dosing
19
Q
Traditional IV UFH in the acute treatment of VTE may be replaced by:
A
1) LMWH
2) Fondaparinux
20
Q
Elimination of LMWH and fondaparinux is dependent on:
A
Renal function
21
Q
Can you give UFH to acute VTE patients with CrCL < 30 mL/min?
A
YES
22
Q
Why did Low-Molecular-Weight Heparin (LMWH) replace UFH for initial VTE treatment?
A
1) Improved pharmacokinetic and pharmacodynamic profiles
2) Ease of use
23
Q
How is LMWH given?
A
Subcutaneously in fixed or weight-based doses
24
Q
Is LMWH given subcutaneously in fixed or weight-based doses as effective as UFH given
intravenously for the treatment of VTE?
A
YES
25
LMWHs have reduced need for:
Laboratory monitoring
26
LMWH monitoring is indicated in:
1) Obesity
2) Pregnancy
3) Children
27
How is LMWH monitored?
By anti–factor Xa activity
28
Anti–factor Xa goal levels are 0.5 - 1.0 unit/mL __-__ hours following subcutaneous LMWH injection.
4 - 6 hours
29
Can LMWH be used on an outpatient basis for stable low-risk patients?
YES
30
In patients without cancer, acute treatment with LMWH is generally transitioned to long-term warfarin therapy after about:
5 - 10 days
31
_____ is preferred if thrombolytic therapy or embolectomy is anticipated.
Rapidly reversible UFH
32
Fondaparinux is dosed ___ via weight-based subcutaneous injection.
Once daily
33
When is Fondaparinux contraindicated?
If CrCL < 30 mL/min
34
Can we give Warfarin monotherapy for acute VTE treatment? Why or why not?
NO, because the slow onset of action is associated with high incidence of recurrent thromboembolism.
35
Warfarin is effective in the long-term VTE management IF:
It is started concurrently with rapid-acting parenteral anticoagulant
36
The initial dose of Warfarin is:
5-10 mg for most patients
37
Warfarin is periodically adjusted to achieve and maintain an INR between:
2-3
38
Which direct oral anticoagulants can be started as single-drug therapy?
1) Rivaroxaban
2) Apixaban
39
How are Rivaroxaban and Apixaban monitored?
None, they don't need to be monitored.
40
Which direct oral anticoagulants require prior parenteral anticoagulation?
1) Dabigatran
2) Edoxaban
41
Can patients with CrCL < 30 mL/min take Edoxaban?
Yes, at half the dose.
42
Can patients with CrCL < 30 mL/min receive Dabigatran?
NO
43
Most VTE cases require only ___ therapy.
Anticoagulation
44
What are Thrombolytic agents?
Proteolytic enzymes
45
What do Thrombolytic agents do?
Enhance conversion of plasminogen to plasmin, which lyses the thrombus.
46
Thrombolytic therapy improves:
Early venous patency
47
Does Thrombolytic therapy improve long-term outcomes?
NO
48
How should you adjust anticoagulation therapy duration and intensity for DVT patients receiving thrombolysis?
No change
49
Patients with DVT involving the iliac and common femoral veins are at highest risk of:
Post-thrombotic syndrome
50
Patients at high risk for post-thrombotic syndrome may benefit from:
Thrombus removal
51
Which patients are at highest risk for post-thrombotic syndrome?
Patients with DVT involving the iliac and common femoral veins
52
In acute PE management, successful clot dissolution with thrombolytic therapy:
1) Reduces elevated pulmonary artery pressure
2) Improves right ventricular dysfunction
53
For thrombolytic therapy to be used, the risk of ___ should outweigh the risk of ___ from thrombolytic therapy.
Death from PE; Serious bleeding
54
Prior to initiating Thrombolytic therapy, what should patients be screened carefully for?
Contraindications related to bleeding risk
55
Which anticoagulant crosses the placenta?
Warfarin
55
Which anticoagulants are preferred in pregnancy?
1) UFH
2) LMWH
56
What are the complications of taking Warfarin during pregnancy?
1) Fetal bleeding
2) CNS abnormalities
3) embryopathy
57
Pregnant women with a history of VTE should receive VTE prophylaxis for how long after
delivery?
6-12 weeks
58
Which anticoagulants are safe during breast-feeding?
1) Warfarin
2) UFH
3) LMWH
59
VTE in pediatric patients is increasing secondary to:
1) Prematurity
2) Cancer
3) Trauma
4) Surgery
5) Congenital heart disease
6) SLE
60
Pediatric patients rarely experience ___(provoked/unprovoked) VTE
Unprovoked
61
Pediatric patients often develop DVT associated with:
Indwelling central venous catheters
62
How do you give pediatric patients anticoagulation with UFH and warfarin?
Similar to that of adults
63
Why is obtaining blood from pediatric patients for coagulation monitoring tests problematic?
Because of poor venous access
64
Which anticoagulant is preferred in pediatric patients?
LMWH
65
Why is LMWH preferred in pediatric patients?
1) Low drug interaction potential
2) Less frequent lab testing
66
Warfarin should be continued in pediatric patients for at least ____ for provoked VTE.
3 months
67
Warfarin should be continued in pediatric patients for at least ____ for unprovoked VTE.
6 months
68
Is routine use of thrombolysis and thrombectomy recommended in children?
NO
69
Cancer-related VTE is associated with:
1) Higher rates of recurrent VTE
2) Higher rates of bleeding
3) More resistance to standard warfarin-based therapy
70
Warfarin therapy in cancer patients is often complicated by:
1) Drug interactions (chemotherapy and antibiotics)
2) The need to interrupt therapy for invasive procedures
71
Why is maintaining a stable INR difficult in cancer patients?
1) Nausea
2) Anorexia
3) Vomiting
72
________ for cancer-related VTE decreases recurrent VTE rates without increasing bleeding risks compared with warfarin-based therapy.
Long-term LMWH monotherapy
73
LMWH therapy for cancer-related VTE should be used for at least the first ___ of long-term treatment
3 - 6 months
74
Anticoagulation therapy for cancer-related VTE should continue for as long as:
1) The cancer is “active”
2) While the patient is receiving chemotherapy
75
__ is preferred for acute VTE treatment in renal dysfunction.
UFH
76
Why can't LMWH, fondaparinux, and direct-acting anticoagulants (DOACs) be used in renal dysfunction?
Because they accumulate
77
Patients with chronic kidney disease are at increased risk of __ from other causes.
Bleeding
78
Unfractionated heparin is a heterogeneous mixture of ___ of variable lengths.
Sulfated mucopolysaccharides
79
How is the anticoagulant effect of UFH mediated?
Through a specific pentasaccharide sequence that binds to antithrombin.
80
UFH accelerates the anticoagulant action of ___ 100 - 1,000 times.
Antithrombin
81
Antithrombin inhibits factors:
2, 9, 10, 12
82
UFH prevents:
Thrombus growth and propagation
83
UFH prevents thrombus growth and propagation allowing:
Endogenous thrombolytic systems to dissolve the clot.
84
Which 2 factors are most sensitive to UFH–antithrombin complex inhibition?
2 (Thrombin) and 10
85
In order to inactivate thrombin (IIa), the heparin molecule must first form what?
A ternary complex bridging between antithrombin and thrombin
86
The inactivation of factor Xa requires UFH binding to antithrombin via:
The specific pentasaccharide sequence
87
The onset of action of UFH after SC injection is:
1-2 hours
88
The action of UFH peaks at:
3 hours
89
Why should intramuscular UFH be avoided?
Because of the risk of bleeding and hematomas
90
UFH has a dose-dependent half-life of:
30-90 minutes
91
UFH's elimination follows __(zero/first) order kinetics.
Zero
92
What are the Adverse Effects of UFH?
1) Bleeding
2) Heparin-induced thrombocytopenia (HIT)
3) Significant bone loss and osteoporosis
93
What can you give to reverse the anticoagulant effects of UFH?
Protamine sulfate
94
How quickly does Protamine sulfate act?
5 minutes
95
What is Heparin-induced thrombocytopenia (HIT) caused by?
Pro-thrombotic antibodies that bind to complexes of heparin and platelet factor 4 (PF4)
96
Heparin-induced thrombocytopenia (HIT) leads to:
Arterial thromboembolic events
97
Heparin-induced thrombocytopenia (HIT) occurs ____ after initiation of UFH.
5-10 days
98
What alternative anticoagulants can be given if the patient experiences Heparin-induced thrombocytopenia (HIT)?
Direct thrombin inhibitors
99
What represents vaccine-related variant of HIT?
Vaccine-induced immune thrombotic thrombocytopenia (Ex. Thrombosis seen with some Covid-19 vaccines is similar to HIT)
100
When used for more than 6 months, such as in pregnancy, UFH can cause:
Significant bone loss and osteoporosis
101
Which drugs can't be used with UFH out of fear of increased bleeding?
1) Anticoagulants
2) Thrombolytics
3) Antiplatelet agents
4) Aspirin
5) NSAIDs
102
How is LMWH produced?
By depolymerization of UFH
103
Which is lighter in weight: LMWH or UFH?
LMWH
104
Advantages of LMWH?
1) Predictable anticoagulation dose response
2) Improved subcutaneous bioavailability
3) Dose-independent elimination (first-order)
4) Longer half-life
5) Reduced need for routine laboratory monitoring
105
Which drugs are LMWH?
1) Enoxaparin
2) Dalteparin
106
How does Low-molecular-weight heparin (LMWH) prevent thrombus growth and propagation?
By enhancing and accelerating the activity of antithrombin against factor Xa
107
Because of smaller chain lengths, LMWH has limited activity against:
Activated thrombin (IIa)
108
The bioavailability of LMWH is __% after SC injection.
90%
109
The peak anticoagulation of LMWH is between __-__ hours.
3 - 5
110
LMWH is mainly eliminated by:
Renal excretion
111
Adverse Effects of LMWH?
1) Bleeding
2) HIT
3) Osteoporosis and osteopenia
112
Antidote for LMWH?
IV protamine sulfate
113
HIT in LMWH is three times __(higher/lower) than that observed with UFH.
Lower
114
LMWH should be avoided in patients with __, because of cross reactivity with antibodies.
HIT
115
Which drugs can't be used with LMWH because of drug-drug interactions (increased bleeding)?
1) Anticoagulants
2) Thrombolytics
3) Antiplatelet agents
4) Aspirin
5) NSAIDs
6) Dipyridamole
7) Sulfinpyrazone
116
Fondaparinux is a synthetic molecule consisting of the active pentasaccharide units that bind __(irreversibly/reversibly) to antithrombin.
Reversibly
117
Fondaparinux is a synthetic molecule consisting of the active pentasaccharide units that bind reversibly to ___.
Antithrombin
118
Fondaparinu**x** inhibits:
Factor **X**a activity ONLY
119
Fondaparinux is eliminated __(unchanged/changed) in the urine.
Unchanged
120
Elimination half-life of Fondaparinux is:
19 hours
121
The anticoagulant effect of Fondaparinux persists for ___ following discontinuation of the drug in patients with normal renal function.
2 to 4 days
122
Adverse Effects of Fondaparinux?
1) Bleeding
2) Rare cause of HIT
123
Fondaparinux antidote?
NONE
124
Which drugs can't be used with Fondaparinux because of drug-drug interactions (increased bleeding)?
1) Anticoagulant
2) Fibrinolytics
3) Antiplatelets
125
Hirudin is derived from ___.
Leech
126
Lepirudin is from:
Recombinant DNA technology
127
What is Lepirudin?
Irreversible inhibitor, inactivates fibrin-bound thrombin.
128
How is Lepirudin given?
1) IV
2) SC
129
Lepirudin is monitored by:
aPTT
130
How is Lepirudin eliminated?
1) Hepatic metabolism
2) Renal excretion
131
Lepirudin should not be given in:
Renal failure
132
Lepirudin is used for:
Thrombosis related to HIT
133
Antidote for Lepirudin?
NONE
134
What is Bivalirudin?
Direct thrombin inhibitor
135
Bivalirudin is a synthetic congener of the naturally occurring anticoagulant ___.
Hirudin
136
How is Bivalirudin given?
IV bolus followed by infusion
137
How is Bivalirudin eliminated?
1) Hepatic elimination
2) Renal elimination
3) Proteolytic cleavage
138
Bivalirudin __(reversibly/irreversibly) inhibits both circulating and clot-bound thrombin.
Reversibly
139
Bivalirudin inhibits:
1) Circulating thrombin
2) Clot-bound thrombin
3) Thrombin-mediated platelet activation and aggregation
140
Does Bivalirudin have a higher or lower bleeding risk than r-hirudins?
Lower
141
Bivalirudin is used in:
1) Percutaneous coronary intervention (PCI)
2) HIT
142
How is Bivalirudin monitored?
Thrombin Inhibitor Assay
143
Why is Thrombin Inhibitor Assay better than aPTT?
Because it is NOT affected by antiphospholipid antibodies
144
Bivalirudin is contraindicated in:
Severe renal impairment
145
Vitamin K in its reduced form is required for vitamin K-dependent carboxylation of:
1) Factors 2, 7, 9, and 10
2) Proteins C and S
146
What does Warfarin do?
Inhibits the reduction of vitamin K epoxide = Impairs the formation of complete functioning clotting factors
147
How long does it take for Warfarin to achieve its full antithrombotic effect?
6 days
148
Why does it take so long for Warfarin to work?
Because it has NO effect on pre-formed clotting factors
149
The time required for warfarin to achieve its pharmacologic effect is dependent on:
Coagulation protein elimination half-lives (6 hours for factor 7 and 72 hours for prothrombin (2))
150
Half-life of Factor 2? (**Two**)
72 hours (**Too** long)
151
Half-life of Factor 7? (**S**even)
6 hours (**S**hort)
152
Half-life of Factor 9?
24 hours
153
Half-life of Factor 10?
40 hours
154
Half-life of Protein C?
8 hours
155
Half-life of Protein S?
30 hours
156
Warfarin has a __(wide/narrow) therapeutic index.
Narrow
157
Adverse Effects of Warfarin?
1) Bleeding
2) Purple Toe Syndrome
3) Warfarin-induced skin necrosis
158
Warfarin antidote?
Vitamin K
158
In case of bleeding, warfarin should be:
1) Temporarily stopped
2) Dose reduced
158
What causes Purple Toe Syndrome?
Cholesterol microembolization into the arterial circulation of the toes
159
Which areas of the body are most commonly affected by Warfarin-induced skin necrosis?
Areas rich in subcutaneous fat:
1) Breasts
2) Thighs
3) Buttocks
4) Abdomen
160
How is Warfarin monitored?
INR
161
Which drugs cause pharmacodynamic interactions with Warfarin?
1) Aspirin/NSAIDs
2) Clopidogrel/Ticlopidine
3) Tramadol
4) Levothyroxine
5) Vitamin K containing foods/supplements
162
What does Tramadol do when given with Warfarin?
Elevates INR
163
What does Levothyroxine do when given with Warfarin?
Increases catabolism of clotting factors
164
Which drugs elevate the INR when given with Warfarin?
1) Amiodarone
2) Fluoroquinolones
3) Trimethoprim/Sulfamethoxazole
4) Metronidazole
5) Azole antifungals
6) Statins
7) Isoniazid
8) NSAIDs
9) Sertraline
10) Gemfibrozil
11) Ethanol
12) Macrolides
13) Cimetidine
14) Omeprazole
15) Fluorouracil
16) Garlic!!
17) Gingko
18) Vitamin E
165
Which drugs reduce the INR when given with Warfarin?
1) Rifampin
2) Barbiturates
3) Carbamazepine
4) Phenytoin
5) St. John's Wort
6) Smoking
7) Cholestyramine (Bile Binding Resins)
8) OCPs (Estrogen)
9) Ginseng
10) Green tea
11) Avocado
12) Leafy greens
166
Which enzyme metabolizes Warfarin?
CYP2C9
167
Why does warfarin exhibit dose variability between patients?
Polymorphisms in:
1) CYP2C9
2) The gene coding for VKOR (Vitamin K Epoxide Reductase)
168
Which metabolizer subtypes have been associated with increased risk of bleeding on Warfarin?
Poor metabolizers
169
Warfarin resistance can be due to:
Mutations in the receptor gene
170
Which drugs are Direct Oral Anticoagulants?
1) Rivaro**x**aban
2) Api**x**aban
3) Edo**x**aban
4) Dabigatran
171
What do Rivaroxaban, Apixaban, and Edoxaban do?
Selectively inhibit both free and clot-bound factor Xa.
172
True or False: Rivaroxaban, Apixaban, and Edoxaban require antithrombin to exert their anticoagulant effect.
FALSE; THEY DO NOT REQUIRE IT.
173
What is Dabigatran?
A selective, reversible, prodrug that directly inhibits factor IIa (Thrombin)
174
Direct Oral Anticoagulants should be avoided in:
Renal failure (CrCl < 30 mL/min)
175
Which last longer: Factor 10 inhibitors or Dabigatran?
Dabigatran
176
Rivaroxaban and apixaban are substrates of:
1) Cytochrome CYP3A4
2) P-glycoprotein
177
Indications for using Rivaroxaban and Apixaban?
1) Prevent VTE following hip or knee replacement surgery
2) Extended VTE treatment after the first 6 months of anticoagulant therapy
178
Which drugs are substrates of Cytochrome CYP3A4 and P-glycoprotein?
1) Rivaroxaban
2) Apixaban
179
Indications for using Dabigatran?
Extended VTE treatment after the first 6 months of anticoagulant therapy
180
Adverse Effects of Direct Oral Anticoagulants?
1) GI complaints
2) Bleeding
181
Antidote for Dabigatran?
1) Idarucizumab
2) Hemodialysis
182
Antidote for Direct Oral Anticoagulants?
Activated charcoal within 2 hours of presentation
183
How does Idarucizumab work to stop the effects of Dabigatran?
It binds to dabigatran and its acylglucuronide with higher affinity than that of dabigatran to thrombin.
184
When is Idarucizumab used?
Dabigatran severe side effects:
1) Life-threatening bleeding
2) When there is need for urgent surgical intervention
185
ALL Direct Oral Anticoagulants should not be given with:
1) P-glycoprotein inducers
2) P-glycoprotein inhibitors
186
Rivaroxaban and Apixaban should not be given with:
1) CYP3A4 inducers
2) CYP3A4 inhibitors
187
What should we assess when giving Direct Oral Anticoagulants?
Renal function
188
___ dosing should be reduced in patients with CrCL 15 - 50 mL/min
Edoxaban
