VTE Flashcards
(140 cards)
1
Q
What is a DVT?
A
a blood clot within a deep vein
2
Q
What is a PE?
A
a blockage caused by a blood in clot in the pulmonary arteries
3
Q
What is Virchow’s triad?
A
3 primary factors influencing formation of a pathogenic clot
- damage to the vessel wall
- venous stasis -hypercoagulable state
4
Q
What is the function of antithrombin?
A
inhibits thrombin (IIa), factor IXa, and factor Xa
5
Q
What is the function of protein S?
A
cofactor for activation of protein C
6
Q
What is the function of protein C?
A
inactivates factors Va and VIIa
7
Q
What is the function of tissue factor pathway inhibitor (TFPI)?
A
binds to factor VIIa-tissue factor complex and inhibits activation of factor X
8
Q
What is the function of plasminogen?
A
converted to plasmin via tissue plasminogen activator (t-PA)
9
Q
What is the function of plasmin?
A
lyses fibrin to form fibrin degradation products
10
Q
Where are the most common locations of clot formation?
A
- muscular veins of the calf
- valve cusp pockets of the deep calf veins
11
Q
DVT once formed can:
A
- spontaneously lyse
- extend into more proximal veins
- embolize to the lungs causing PE
12
Q
What are the clinical presentation/symptoms of DVT?
A
- unilateral calf or leg swelling
- calf pain or tenderness
- erythema
- warmth
- palpable cord
- Homan’s sign
13
Q
What are the clinical presentation/symptoms of PE?
A
- dyspnea
- pleuritic chest pain
- anxiety
- tachypnea (>20 breaths/min)
- tachycardia
- cough
- hemoptysis
- diaphoresis
14
Q
What is a D-dimer?
A
cross linked fibrin degradation fragment produced during clot dissolution that has a negative predictive value of
15
Q
What are some non-invasive tests used to diagnose DVT?
A
- Doppler ultrasonography
- B-mode compression ultrasound
16
Q
What are some invasive tests used to diagnose DVT?
A
Contrast venography-radiographic visualization of the involved vessels with injection of radiocontrast material
17
Q
What diagnostic test is the gold standard for diagnosing DVT?
A
contrast venography
18
Q
What is the most commonly used diagnostic test used for diagnosing a PE?
A
Chest CT with contrast
19
Q
What diagnostic test is the gold standard for diagnosing PE?
A
pulmonary angiography
20
Q
What is the most invasive test used to diagnose PE?
A
pulmonary angiography
21
Q
What are ancillary tests used to diagnose PE?
A
- arterial blood gas
- EKG
- CXR
22
Q
What is bridge therapy?
A
When a parenteral agent and warfarin are given together for a minimum of 5 days and until the INR is less than or equal to 2 for at least 24 hours
23
Q
What are the parenteral agents?
A
- UFH
- LMWH
- Fondaparinux
24
Q
Per CHEST guidelines, what parenteral agents are recommended over the other?
A
LMWH and Fondaparinux are recommended over UFH
25
What is the structure of UFH?
heterogenous mixture of glycosaminoglycan polysaccharide chains
26
What is the MOA of UFH?
binds to antithrombin via a unique pentasaccharide sequence and accelerates its interaction and inactivation of thrombin and factor Xa by 1000-fold
27
What other factors does UFH inhibit?
IXa, XIa, XIIa
28
Inhibition of thrombin requires a heparin chain that is at least _________ in length
18 saccharide units
29
What is the route of administration for the treatment of VTE?
continuous infusion
30
What is the route of administration for the prophylaxis of VTE?
subcutaneous injection, NOT intramuscular
31
What is intravascular binding?
creates variability and unpredictability in patient response
32
What do you monitor when a patient is on UFH?
- aPTT (activated partial thromboplastin time)
- platelet counts, Hgb, Hct
- signs/symptoms of bleeding
33
What is the dosing of UFH for VTE treatment?
IV bolus of 80 units/kg followed by 18 units/kg/hr continuous IV infusion with no renal adjustment
34
What is the dosing of UFH for VTE prophylaxis?
5000 units SC q8h with no renal adjustment
35
What are some adverse effects of UFH?
- bleeding
- Heparin-induced thrombocytopenia (HIT)
- Heparin-induced osteoporosis
36
How can bleeding be reversed when on UFH?
reversed with IV bolus of protamine sulfate which binds to heparin to form a table salt
37
What is type 1 HIT?
transient fall in platelets due to a direct effect of heparin
38
What is type 2 HIT?
immune-mediated reaction
39
What is the mechanism of type 2 HIT?
IgG antibodies directed at heparin-platelet factor 4 complexes
40
What is the treatment of type 2 HIT?
direct thrombin inhibitors Argatroban and Bivalirudin
41
What is the mechanism of heparin-induced osteoporosis?
binding of heparin to osteoblasts
42
What is the structure of LMWH?
heterogenous mixture of of glycosaminoglycans derived from chemical or enzymatic degradation of UFH (~1/3 of molecular weight of UFH)
43
What is the MOA of LMWH?
binds to antithrombin via a unique pentasaccharide sequence. Accelerates inactivation of factor Xa
44
What is the route of administration of LMWH?
subcutaneous injection
45
What is a product of LMWH?
Enoxaparin (Lovenox)
46
Is routine anticoagulation testing necessary in patients taking LMWH?
It is not recommended
47
What test could you perform to monitor patients on LMWH?
anti-factor Xa levels
48
When are anti-factor Xa levels drawn?
4 hours after steady state is reached (after 3rd dose)
49
When should anti-factor Xa levels be drawn?
- patients with a total body weight of \>150 kg or BMI \>50 kg/m2
- if LMWH are used in patients with renal dysfunction
50
What is the dosing of enoxaparin for the treatment of VTE?
1 mg/kg SC q12h or 1.5 mg/kg SC q24h
Renal adjustment: 1 mg/kg SC q24h (CrCl \<30 mL/min)
51
What is the dosing of enoxaparin for the prophylaxis of VTE?
40 mg SC q24h
Renal adjustment: 30 mg SC q24h (CrCl \<30 mL/min)
52
What is the preferred parenteral anticoagulant if a patient is obese and CrCl \<30 mL/min?
UFH
53
What are some adverse effects of LMWH?
- bleeding
- heparin-induced thrombocytopenia (HIT)
- perispinal hematoma
54
What is the antidote used to reverse the effects of LMWH and what is its dose?
- Protamine sulfate
- LMWH administered within 8 hours: 1 mg protamine per 100 anti-factor Xa units (this is 1 mg of enoxaparin)
- a second dose of 0.5 mg protamine per 100 anti-factor Xa units if bleeding continues
55
What is a perispinal hematoma?
increased risk when antithrombotic medications are administered concomitantly with neuraxial blockade
56
What is the MOA/structure of Fondaparinux?
a synthetic analog of the pentasaccharide sequence that binds to antithrombin
57
What is the half-life of UFH?
30-60 min
58
What should you monitor when a patient is on LMWH?
- anti-factor Xa levels
- assess baseline renal function
- signs and symptoms of bleeding
- platelet counts, Hgb, Hct
59
What is the half-life of fondaparinux?
17 hours
60
What is the route of administration of fondaparinux?
subcutaneous injection
61
Where does excretion occur with fondaparinux?
excreted in the urine
62
What should you monitor in patients taking fondaparinux?
- routine anticoagulation testing not required
- assess baseline kidney function
- signs and symptoms of bleeding
- platelet counts/ Hgb/ Hct
63
Do not use fondaparinux in patients with \_\_\_\_\_\_\_\_\_\_\_
CrCl \<30 mL/min
64
What is the dosing of fondaparinux for the treatment of VTE?
- for PTs \<50 kg: 5 mg SC q24h
- for PTs 50-100 kg: 7.5 mg SC q24h
- for PTs \>100 kg: 10 mg SC q24h
65
What is the dosing of fondaparinux for prophylaxis of VTE?
2.5 mg SC q24h
66
What are some adverse effects with fondaparinux?
bleeding (increased risk in patients with smaller weights)
- contraindicated for prophylaxis in patients who weight \<50 kg
- no antidote for reversal
67
What is the relationship between fondaparinux and HIT?
can use fondaparinux in patients with a history of HIT
68
What is the MOA of warfarin?
inhibits the activation of coagulation factors by inhibiting vitamin K dependent carboxylation of the factors
-warfain inhibits vitamin K oxide reducatse enzyme complex (VKORC) therefore inhibiting vitamin K activation which then stops carboxylation
69
What coagulation factors are affected with the use of warfarin?
Factors VII, IX, X, and II
70
What anticoagulation factors are affected with the use of warfarin?
Protein C and S
71
What is the structure of warfarin?
racemic mixture of S- and R- enantiomers
72
Which enantiomer of warfarin is more potent?
S- enantiomer
73
True or False: warfarin has a high bioavailibility and is highly bound to plasma proteins (primarily albumin)?
true
74
What is the onset of anticoagulation action of warfarin?
takes 5-7 days to obtain peak anticoagulant effects
75
What is the half-life of warfarin?
36-42 hours (takes 3-5 days to reach steady state)
76
Where is warfarin metabolized?
in the liver
77
What 2 nucleotide polymorphisms account for up to 50% of the interindividual variability of warfarin response?
VKORC1 and CYp450 2C9
78
Mutation of CYP 2C9 leads to \_\_\_\_\_\_\_\_\_
poor metabolism of warfarin (will require lower doses)
79
Which genetic variations of CYP 2C9 have shown the highest risk of bleeding?
CYP 2C9\*2 and CYP 2C9\*3 (\*2 and \*3 refers to the alleles)
80
VKORC1 genotype determines ________ and what dose AA, GG, and AG mean?
sensitivity to warfarin
- AA: sensitive= need lower dose of warfarin
- GG: resistant= need higher doses of warfarin
- AG= usual dose
81
What should be monitored if a patient is taking warfarin?
- Prothrombin time (PT)
- INR
- signs/symptoms of bleeding
82
What is the goal INR range for patients?
2-3
83
What is the goal INR range for patients with mechanical heart vavles?
2.5-3.5
84
What is the frequency monitoring for INR goals? (hospitalized patients, outpatients, and stable patients)
- Hospitalized patients: daily
- Outpatients: within 3 days of hospital discharge and then weekly
Once a stable response achieved: every 4 weeks and some patients every 12 weeks
85
What is the normal starting dose of warfarin?
5 mg
86
How can warfarin be reveresed?
- Vitamin K
- Kcentra
87
What Kcentra, what is it indicated for, and how is dosing based?
- Prothrombin complex concentrate
- indicated for acute major bledding or when patient needs urgent surgery/invasive procedure
- dosing based on patient's current INR and body weight
88
True or False: Kcentra does not need to give with vitamin K?
false
89
What is Kcentra contraindicated with?
contraindicated in patients with a history of HIT because it contains heparin
90
What is the dosing of Kcentra?
Pre-treatment INR
2 - \<4
4-6
\>6
Dose of Kcentra/kg body weight
25
35
50
Maximum dose
2500
3500
5000
91
What is the MOA of rivaroxaban?
selectively blocks the active site of factor Xa without requiring a cofactor
- inhibits factor Xa in both the intrinsic and extrinsic pathways
- inhibition of clot bound factor Xa
92
What is the half-life of rivaroxaban?
5-9 hours
93
True or false: rivaroxaban is 90% bound to plasma proteins?
true
94
Where is rivaroxaban metabolized and excreted?
hepatic metabolism and excreted in urine and feces
95
What drug-drug interactions does rivaroxaban have?
strong 3a4 and P-glycoprotein inhibitors
96
What is the dosing of rivaroxaban for the treatment of VTE?
15 mg bid with food for the first 21 days, then 20 mg once daily with food
(avoid use in patients with CrCl \<30 mL/min (for VTE treatment, VTE prevention, and hip/knee surgery))
97
What is the conversion from warfarin to rivaroxaban?
discontinue warfarin and start INR is \<3.0
98
What is the conversion from other anticoagulants (besides warfarin) to rivaroxaban?
discontinue agen and start rivaroxaban 0-2 hours prior to the next scheduled dose of previous agent
99
State the clinical trials for rivaroxaban
- Einstein DVT
- Einsten PE
100
What is the MOA/structure of Dabigatran?
a direct thrombin inhibitor- inhibits free and clot-bound thrombin and thrombin-induced platelet aggregation
101
How is dabigatran absorbed and how is eliminated?
- rapid absorption: peak concentration reached within 2 hours
- renal elimation (~80% of total clearance)
102
What is the half-life of dabigatran?
12-17 hours
103
What drug-drug interactions does dabigatran have?
P-glycoprotein inhibitors (may increase concentration of dabigatran)
104
When should treatment of dabigatran begin?
VTE treatment after the aptient has received a parenteral anticoagulant for 5-10 days
105
What is the dosing of dabigatran?
150 mg bid for CrCl \>30 mL/min
(CrCl \<30 mL/min, no dosing recommendations)
106
When should a patient avoid use of dabigatran?
in patients with CrCl \<50 mL/min and use of P-gp inhibitors
107
What is the conversion from warfarin to dabigatran?
discontinue warfarin and start dabigatran when INR \<2.0
108
What is the conversion from a parenteral anticoagulant to dabigatran?
start dabigatran 0-2 hours before the time that the next dose of the parenteral drug would be administered or at the time of the discontinuation of IV heparin
109
What are some adverse effects of dabigatran?
- bleeding (dose dependent increase in the incidence of major GI bleeding, no available antidote)
- GI effects: dyspepsia
110
State the clinical trials for dabigatran
RECOVER, RECOVER II, RE-MEDY, AND RE-SONATE
111
What is the MOA/structure of apixaban?
direct factor Xa inhibitor, inhibits both free and clot-associated factor Xa activity
112
What is the route of administration for apixaban and how is metabolized and excreted?
- oral administration (not affected by food)
- metabolized by CYP enzymes (mainly 3A4)- avoid strong 3A4 inhibitors
- eliminated in the urine (25%) and feces
113
What is the half-life of apixaban?
prolonged abosorption therefore half-life is ~12 hours with repeat dosing (onset 3-4 hours)
114
What are some drug-drug interactions with apixaban?
- 5 mg dose should be reduced to 2.5 mg bid when co-administered with strong CYP3A4 and P-gp inhibitors
- if patient already on 2.5 mg bid dose and started on a strong CYP3A4 and P-gp inhibitor, avoid use
115
What should be monitored when on apixaban?
- Hgb, Hct, platelets
- signs and symptoms of bleeding
- drug-drug interactions
- renal function, body weight
116
What is the dosing for apixaban?
10 mg bid for 7 days, then 5 mg bid
117
What is the conversion from warfarin to apixaban?
start apixaban when INR \<2.0
118
What is the conversion between apixaban and other anticoagulants (other than warfarin)?
discontinue one and start the other at the time of the next scheduled dose
119
Stat the clinical trials for apixaban
AMPLIFY, AMPLIFY-EXT
120
What is the MOA/structure of edoxaban?
factor Xa inhibitor
121
What is the route of administration, metabolism, and excreted for edoxaban?
- oral administration (food dose not affect it, peak plasma concentration 1-2 hours)
- Metabolism: mostly in the unchanged form in plasma; minimal metabolism by hydrolysis, conjugation, oxidation by CYP3A4
- Elimination: unchanged in urine (50%) also biliary/intestinal excretion
122
What is the half-life of edoxaban?
10-14 hours
123
What should be monitored when on edoxaban?
- Hbg, Hct, platelets
- signs/symptoms of bleeding
- renal function and body weight
124
What is the dosing of edoxaban?
- 60 mg qd after 5-10 days of treatment with a parenteral anticoagulant
- reduce dose to 30 mg qd for patients with CrCl 15-50 mL/min, weight less than 60 kg, or take concomitatn P-gp inhbitors
125
What is the conversion from warfarin to edoxaban?
discontinue warfarin and start edoxaban when INR \<2.5
126
What is the conversion from UFH to edoxaban?
discontinue UFH and start edoxaban 4 hours later
127
What is the conversion from other anticoagulants (not warfarin) to edoxaban (and vice-versa)?
discontinue one and start the new drug at the time of the next dose of the previous agent
128
State the clinical trial for edoxaban
Hokusai VTE study
129
What is the duration of therapy for the 1st episode of DVT or PE secondary to a reversible risk factor?
treatment for 3 months
130
What is the duration of therapy for the 1st episode of idiopathic (unprovoked) DVT or PE?
treatment for at least 3 months (then evaluate risk-benefit ratio or extended therapy)
131
What is the duration of therapy for two or more episodes of DVT or PE?
indefinite treatment
132
What are some additional therapy options for treatment of VTE?
- thrombolysis
- inferior vena cava filter
133
When should a patient be considered for thrombolysis therapy?
- risk of limb gangrene secondary to venous occlusion
- massive PE in hemodynamically unstable patients
- administered systemically or locally via catheter
134
When should a patient be considered for inferior vena cava treatment?
- patients with contraindications to anticoagulation
- patients with recurrent thromboembolism despite adequate anticoagulation
135
What are some mechanical methods for the prevention/prophylaxis of VTE?
- ambulation and physical therapy
- graduated compression stockings (GCS) or elastic stockings (ES)
- intermittent pneumatic compression (IPC) devices
- venous foot pump (VFP)
136
When should mechanical methods for the prevention/prophylaxis of VTE be used?
- in patients who are at high risk of bleeding
- as an adjunct to anticoagulant-based prophylaxis
137
What are some pharmacological methods to prevention/prophylaxis of VTE?
- general surgery for acutely ill medical patients
- orthopedic surgery
138
What are the medications and doses for total hip replacement?
DOC: enoxaparin 40 mg SC q 24 hr or enoxaparin 30 mg SC q 12 hr (crcl \<30 use enoxaparin 30 SC q 24 hr)
Other agents: fondaparinux 2.5 mg SC q 24 hr, rivaroxaban 10 mg po q 24 hr, or warfarin (INR goal 2-3), apixaban 2.5 mg po twice daily, dabigatran (recommended in CHEST but not FDA approved), aspirin
139
What are the medications and doses for total knee replacement?
DOC: enoxaparin 30 mg SC q 12 hr (crcl \<30 enoxaparin 30 mg SC q 24 hr)
Other agents: fondaparinux 2.5 mg SC q 24 hr, rivaroxaban 10 mg po q 24 hr, warfarin (INR goal 2-3), apixaban 2.5 mg po twice daily, dabigatran (recommended in CHEST but not FDA approved), aspirin
140
