Anticoagulants - LeBlanc Flashcards
1
Q
Desmopressin Acetate is a (anti/pro) coagulant
A
procoagulant
2
Q
Aspirin, Plavix, and ReoPro are (anticoag/antiPLT)
A
antiPLT
3
Q
Factor IIa and Xa inhibitors, coumadin, LMWH and unfrac’d heparin are (blank)
A
anticoags
4
Q
What is streptokinase?
A
A thrombolytic agent like tPA
5
Q
Protamine sulfate and aminocaproic acid can be given in the event of an overdose of what drug?
A
tPA
6
Q
For what three reasons does little to know intravascular coagulation occur?
A
- dilution of factors
- presence of plasma inhibitors
- activated clotting factors are removed quickly by the liver
7
Q
TXA2 and Serotonin released from the PLTs have what effect of vascular tone?
A
causes powerful vasoconstriction of vascular smooth muscle
8
Q
The (blank) pathway occurs from trauma to the blood itself from large glycoprotein complexes released from PLTs
A
intrinsic pathway
9
Q
The (blank) pathway occurs from extravascular trauma forming a macromolecular complex with tT
A
extrinsic pathway
10
Q
What drug prevents the conversion of plasminogen to plasmin?
A
Aminocaproic acid
11
Q
What two drugs are able to convert plasminogen to plasmin without going through an activation step?
A
tPA and urokinase
12
Q
Streptokinase bound to its proactivator forms (blank), which can convert plasminogen to plasmn
A
anistreplase
13
Q
Plasmin favors the degradation of what two molecules?
A
Fibrinogen and fibrin
14
Q
What are the three direct acting anticoagulants?
A
CHF:
Calcium chelators
Heparin
Factor IIa and Xa inhibitors
15
Q
What are calcium chelators used for?
A
in vitro testing ( aka sodium citrate and EDTA)
16
Q
What is the commonly used indirect anticoagulant?
A
Warfarin
17
Q
What is the most commonly used antiPLT drug?
A
aspirin
18
Q
(blank) is used to activated the intrinsic pathway
A
kaolin
19
Q
T/F: heparin is only active in vivo
A
false; active in vivo and vitro
20
Q
what is the source of commercial heparin?
A
bovine lung or porcine intestinal mucosa
21
Q
Describe the MOA of heparin?
A
- forms complex with a2-globulin AT-III and each of the activated proteases of the cascade (kallikrein, XIIa, XIa, Xa, and thrombin)
22
Q
T/F: heparin binds irreversibly to its targets
A
false; is released and rebinds to free AT-III
23
Q
HMWH blocks the conversion of (blank to blank)
A
prothrombin to thrombin
24
Q
Because HMWH blocks the synth of thrombin, fibrinogen cannot be converted to (blank)
A
fibrin
25
What two factors is heparin very good at inhibiting?
Xa and IIa (thrombin)
26
T/F: HMWH can also suppress the activity of factors IXa and VIIIa
false; IXa and XIa
27
At low doses, HMWH primarily neutralizes factor (balnk)
Xa
28
At high doses, HMWH prevents (blank)-induced activation of PLTs, and actvation of factors V and VIII
thrombin-induced PLT activation
29
HIT causes bleeding or clotting?
clotting, heparin should make you bleed but this shit fucks you up so badly it gets reversed
30
T/F: heparin may be given orally
false
31
What is the main route of admin for heparin?
IV
32
How long does it take a subQ injection heparin to reach therapeutic levels?
2-4 hours
33
T/F: IM is a viable route to give heparin, it just takes longer
false; forms hematomas--makes sense
34
T/F: heparin may cross the placenta and is present in breast milk
false
35
What are the half lives in hours of 100, 400, and 800 units of heparin?
1, 2.5, and 5 hours
36
What are the contraindications for heparin use?
```
When bleeding must be avoided:
1. uclerative lesions (GI, cancers)
2. intracranial hemorrhage
3. brain /spinal cord injury
4. pts with thrombocytopenia or history of HIT
5. severe HTN
6 old pts, especially women
7. severe allergies
```
37
What drug can you give if you OD your pt on heparin (OOPS!)
protamine sulfate at 1mg of PS per 100 units heparin, not to exceed 50mg in 10 minutes
38
What is the range that you want the aPTT to be in on heparin thearpy?
1.5 to 2.5x normal
39
When should you begin checking factor Xa activity after beginning heparin?
6 hour intervals after initiation of heparin infusion
40
What two values should you pay attention to on the CBC when giving heparin?
PLT count and Hct
41
HMWH will accelerate the interaction of AT-III with both thrombin and factor Xa while LMHW will only accelerate the interaction with (blank)
factor Xa
42
What is the ratio of anti-Xa: anti-IIa in HMHW treatment?
1:1
43
What is the ratio of anti-Xa:anti-IIa in LMHW treatment?
4:1
44
T/F: HMHW and LMWH are equally effective
TRUE
45
The half life of LMWH is how many times longer than HMHW?
2x
46
What is the bioavailability of LMWH for subQ injection? Of UFH?
LMWH: 90%
| while UFH is only 20%
47
T/F: lmwh has less frequent bleeding compared to HMHW
true
48
T/F: a fib is an indication for heparin
true
49
T/F: blood transfusions is an indication for heparin
true
50
What are the indications for UFH or LMWH use?
```
Blood transfusions
Atrial fibrillation
Disseminated intravascular coagulation (DIC)
Open heart surgery
Pulmonary embolism
Venous thromboembolism
Venous catheter occlusion
```
51
Are thrombin inhibitors direct or indirect anticoagulants?
direct
52
Which thrombin inhibitor is similar in structure to l-arginine?
Argatroban
53
What thrombin inhibitor was isolated from leech saliva?
Hirudin
54
What is the route of admin for thrombin inhibitors?
IV infusion
55
When do you use thrombin inhibitors instead of heparin?
if the pt is high risk for HIT or if they had a coronary angioplasty or coronary bypass surgery
56
What is the only orally active thrombin inhibitor?
Dabigatran
57
What are the indications for using dabigatran?
thromboembolic disorders
| prophylactic anticoag to minimize stroke risk in pts with NON-VALVULAR a-fib
58
What is the route of admin of factor Xa anticoags?
oral
59
What type of drug do you give for DVTs, PE, cerebrovascular accident, or prophylactic or hip or knee replacement?
factor Xa inhibitor Xarelto
60
What do you give for cerebral accidents or non-valvular a-fib (new drug)?
Eliquis
61
What is the most common oral anticoag?
warfarin
62
How long does it take warfarin to become active in vivo?
12-24 hours
63
what is the MOA of warfarin?
blocks vit. K activation of coag factors; specifically blocks the gamma carboxylation of glutamic acid residues
64
What is the effect of warfarin on protein C?
downregulates it
65
When protein C is bound to (blank) on the endothelial cells, it alters the specificity thrombin
thrombomodulin
66
Binding of protein C to the endothelial surface favors the degradation of what two factors>?
Va and VIIIa
67
T/F: warfarin has procoagulant activity early in therapy
true
68
Why does warfarin show procoagulant effects early in treatment
because it downregulates anticoag protein C!
69
What factor has the shortest half life?
VII; 6 hours
70
What factor has the longest half lives?
prothrombin: 60 hours
71
Which factor has a half life of 24 hours?
IX
72
WHich factor has a half life of 40 hours?
X; 40 is a multiple of 10
73
Warfarin is bound to what plasma protein?
albumin
74
How is warfarin metabolized?
CYP450 in the liver
75
How is warfarin excereted?
by the kidney via urine after liver processing
76
The INR and (PT/PTT) is used to test the coag properties of warfarin
PT
77
How do you correct for a warfarin overdose?
give Vit. K after 24 hours
| transfuse whole blood or plasma for major bleeding
78
What are the contraindications for warfarin?
Vit. K deficiency
Hepatic or renal disease
SALICYLATE THERAPY
pregnancy
79
T/F: coumadin can pass the placental barrier
TRUE
80
What is the complication of giving coumadin to pregnant moms?
abortion or birth defects
81
Why are infants more sensitive to anticoagulants?
lower levels of vit. K production due to a lack of gut bacteria to make it
82
What drugs reduce the efficacy of warfarin?
cholestyramine
thoset that induce:
hepatic microsomal enzymes (how its cleared)
stimulation of synth of clotting factors (counteracts it)
83
What drugs increase the response to warfarin?
```
those that:
displace the anticoag from the plasma proteins
inhibit hepatic microsomal enzymes
reduce availability of Vit. K
inhibit synth of clotting factors
decrease PLT aggregation, aka ASPIRIN!!!
```
84
desmopressin acetate is an analog of what natural hormone?
ADH
85
Desmopressin stimulates activity of what factor?
vIII
86
WHat do you use desmopressin to treat?
hemophilia A with VIII levels greater than 5%, or with VIII Abs
87
What is used to treat von Willebrands' type 1?
desmopressin
88
What is the MOA of Aspirin?
inhibits release of ADP by platelets
| inhibits PLT aggregation by acetylating COX which prevents tXA2 production
89
Low dose aspiriin (160-320mg) is more effective at inhibiting (TXA2/PGI2)
TXA2
90
PGI2 is synthesized by the endothelium and has effects opposite to (blank)
TXA2
91
The effect of aspirin is (reversible/irreversible)
irreversible
92
T/F: benefit of aspirin to prevent MI is uncertain
true
93
T/F: benefit of MI in pts with previous vascular accident is uncertain
false; it does help
94
What drug do you use in patients that are at risk of stroke but are intolerant to aspirin?
Ticlopidine
95
What is the MOA of ticlopidine?
inhibits response to ADP; prevents aggregation via imapairing the GpIIb/IIIa receptor
96
What is the mechanism of Plavix?
inhibits response to ADP and aggregation via the GpIIb/IIa pathway like ticlopidine
97
ReoPro is a mAB (blank) fragment of PLT glycoprotein IIb/IIIa
Fab
98
What is the MOA of ReoPro?
prevents binding of fibrinogen and vWF, which prevents PLT aggregation
99
What are in the indications for ReoPro?
acute coronary syndromes and percutaneous coronary intervention
100
Plasminogen is converted to plasmin by the cleavage of how many peptide bonds?
one
101
Plasmin is a (specific/nonspecific) protease
non-specific
102
What is the major scary SE of thrombolytic agents?
hemorrhage at the site of injury
103
why can thrombolytics cause hemorrhage?
they dissolve both the pathological clots and the clot at the actual site of injury
104
(blank) is indicated in pts with extensive pulmonary emboli, sever iliofemoral thrmobophlebitis and acute coronary occlusion
thrombolytic therapy
105
Stasis from vascular occlusion signals for the release of (blank)
tPA
106
tPa binds to (blank) and converts plasminogen
fibrin
107
Free plasmin is rapidly inhibited by (blank)
a2-antiplasmin
108
T/F: fibrin-bound plasmin is resistant to degradation by a2-antiplasmin
true
109
T/F: tPA works to convert plasminogen in the abscence of fibrin
false; works very poorly
110
Does tPA prefer fibrin bound plasminogen or serum plasminogen?
fibrin bound
111
(blank) is produced by b-hemolytic streptococci and forms a stable 1:1 complex with plasminogen
streptokinase
112
what is the enzymatic activity of streptokinase?
none! it doesn't have intrinsic activity, it has to be bound to plasminogen
113
How does binding of streptokinase to plasminogen allow conversion to plasmin?
binding changes the confomration that allows for a peptide bond to be cleaved
114
A pt. with a liver biopsy one week prior who had a puncture of the vena cava (non compressible) after a car accident and needed to be shocked (may/may not) receive thrombolytic therapy for DIC
may not
115
A pt. with a gastric ulcer of two months becomes septic after systemic infection with H. pylori and develops DIC that leads to a ishcemic stroke. Is tPA indicated?
nope; gastric bleeding
116
A patient with chronic hypertension of 130/90 begins coumadin therapy. However, he nonetheless develops a DVT. can tPA be used?
no, HTN above 110
117
A patient with a previous stroke (is/isnot) able to get tPA to clear the stroke
is not
118
What drug can you give to reverse the states associated with fibrinolysis?
aminocaproic acid
119
What are the signs and symptoms of DVT
1. unilateral leg swelling with local tenderness and pain
2. denies SOB; indicates that the DVT has not progressed to PE
3. cyanoiss from venous obstruction or reddish color from perivascular inflammation
120
WHat are risk factors associated with forming a DVT?
1. immobilization
2. coronary artery disease
3. obesity
121
How do you Dx a DVT?
1. Doppler (aka duplex) ultrasound
2. fibrinogen scanning (non invasive, detects areas of accumulation)
3. d-Dimer; tests for fibrin degradation products
4. Impedence plethysmography (pneumatic cuffs to detect blood volume changes)
122
What anticoagulant should be used in the IMMEDIATE treatment of a DVT?
NOT WARFARIN, TOO SLOW
Use heparin IV or subQ LMHW
Elevate the leg and apply heat to help restore blood flow
123
What is the standard dosing regimen of heparin?
5000 U IV for loading dose followed by 1,000 U/hr IV for maintanence dose
124
Why do we give such a large loading dose of heparin?
1. helps reach therapeutic concentration faster
| 2. there is an initial resistance to anti coag drugs because the clotting cascade is in full swing
125
What is the loading dose range of heparin based on body weight?
70-100 U/kg
126
What is the maintenance dose range of heparin based on body weight?
15-25 U/kg/hr
127
What is the soonest after giving a loading heparin dose that you should measure the aPTT?
no sooner than 6 hours
128
If heparin dosing is stable, what three labs should you check once daily?
1. aPTT
2. Hct
3. PLT level
129
How long should heparin be maintained for acute onset DVT?
7-10 days
130
On what day of hepaarin therapy should warfarin be started?
day 5
131
How long should a patient be kept on warfarin after having a DVT?
3-6 months
