Thrombosis And Antithrombotics

Front 1

What 3 components is Vichow's triad composed of?

Back 1

Vessel wall
Circulating elements (factors, activators)
Blood flow

Front 2

Vichow's triad is used for what?

Back 2

keeping homeostasis

Front 3

What are Factors made?

Back 3

liver

Front 4

What risk factors disrupt Virchow's triad?

Back 4

Age
HX of VTE
Venous Stasis
Vascular Injury
Hypercoagulable States
Drug Therapy

Front 5

What is the strongest risk factor of DVT?

Back 5

History OF VTE

Front 6

What kind of surgery is number 1 cause for DVT?

Back 6

knee and hip replacement

Front 7

What kind of drug therapy increases the risk for blood clot?

Back 7

estrogen therapy--> blood clots

Front 8

what are a couple Hypercoaguable states that will disrupt virchows triad?

Back 8

Malignancy, pregnancy, Protein C deficienct

Front 9

What are 5 Anticoagulant classes?

Back 9

Unfractionated heparin
Low-molecular-weight heparins (LMWH)
Factor Xa inhibitors
Direct Thrombin Inhibitors
Vitamin-K antagonists

Front 10

What are 3 drugs (brand/generic) for LMWH

Back 10

enoxaparin (Lovenox®)
dalteparin (Fragmin®)
tinzaparin (Innohep®)

Front 11

What are 3 drugs (brand/generic) for Factor Xa inhibitors?

Back 11

fondaparinux (Arixtra®)
rivaroxaban (Xarelto®)
apixaban

Front 12

What are 5 drugs (brand/generic) for Direct thrombin inhibitors?

Back 12

argatroban
lepirudin (Refludan®)
desirudin (Iprivask®)
bivalirudin (Angiomax®)
dabigatran (Pradaxa®)

Front 13

What is 1 vitamin-K antagonists (brand/generic)

Back 13

Warfarin (Coumadin®)

Front 14

What are 3 antiplatelet classes?

Back 14

Aspirin
ADP Inhibitors (P2Y12 Inhibitors)
Glycoprotein IIb/IIIa inhibitors:

Front 15

What are 4 drugs (brand/generic) for AdP inhibibitors ( P2Y12 Inhibitors)?

Back 15

ticlopidine (Ticlid®)
clopidogrel (Plavix®)
prasugrel (Effient®)
ticagrelor (Brilinta®)

Front 16

What are 3 drugs (brand/generic) for Glycoprotein IIb/IIIa inhibitors:

Back 16

eptifabitide (Integrelin®)
tirofiban (Aggrastat®)
abciximab (ReoPro®)

Front 17

What are 3 drugs (brand/generic) for thrombolytics?

Back 17

alteplase (Activase®)
reteplase (Retevase®)
tenecteplase (TNKase®)

Front 18

Unfractionated Heparin (UFH) is derived from what?

Back 18

Derived from bovine lung or porcine intestine

Front 19

Unfractionated Heparin (UFH) has what MW?

Back 19

MW from 3-30 kDa

Very large molecule

Front 20

Unfractionated Heparin (UFH) has a Unique _____ sequence resulting in affinity to ____
Only ____ have this sequence

Back 20

Unique pentasaccharide sequence resulting in affinity to antithrombin
Only 1/3 have this sequence

Front 21

Unfractionated Heparin (UFH) combines with____and potentiates activity. Most active on ___and ___

Back 21

Combines with ATIII and potentiates activity
Most active on Thrombin (II) and Xa

Front 22

Heparin binds to which antithrombin? what does it inhibit?

Back 22

Heparin binds to anthrombin 3 inhibits 10-10a and thrombin to prothrombin

Front 23

What size molecule is UFH ? Which molecule does it bind to ? UFH has more of a binding affinity for ___ than ___?

Back 23

Because it’s a big molecule, its going to work on prothrombin. Binds to antithrombin 3, because of tail, it will change and bind around thrombin. Binding affinity more for throming instead of 10a.

Front 24

UFH has what kind of dosing availability does it have?

Back 24

No oral avaliablitity, only iv or sc

Front 25

UFH binds to many ___ and ___ in the ___

Back 25

Binds to many proteins and cells in bloodstream

Front 26

UFH has what kind of onset of effect?

Back 26

Onset of effect: 1-2 hours (peak 3 hours)

Front 27

UFH has what half life?

Back 27

30-90 min

Front 28

UFH is primary eliminated how? What patients can't it be used in?

Back 28

Enzymatic degradation is primary elimination route

Patients with kidney problems

Front 29

How is UFH dosed?

Back 29

Dosing- Iv or SC, mostly IV
dosed in units/kg much more dialed down dose

Front 30

What is the gold standard for managin heparin?

Back 30

Activated partial thromboplastin time (aPTT)
Institution and laboratory specific

Front 31

What must be monitored when giving UFH?

Back 31

Activated partial thromboplastin time (aPTT)
Institution and laboratory specific
Activated clotting time (ACT)
OR and cath lab
Antifactor Xa levels
Newer method that standardizes across institutions

Front 32

Does UFH have any drug interactions?

Back 32

Nonsignificant

Front 33

What is the number 1 AE of UFH?

Back 33

Bleeding is #1 adverse event of UFH

Front 34

What are risk factors for bleeding with UFH?

Back 34

Age, recent surgery, heavy alcohol consumption, renal failure, Petic Ulcer Disease , malignancy

Front 35

What is very common wit UFH?

Back 35

Thrombocytopenia

Front 36

What 2 thrombocytopenia diseases can be seen with UFH?

Back 36

Heparin-associated thrombocytopenia (HAT)
Heparin-induced thrombocytopenia (HIT)

Front 37

Describe (HAT) and what should be monitored for it when dosing UFH?

Back 37

Heparin-associated thrombocytopenia (HAT) - benign, transient, rarely <100k Platelet count

Front 38

Describe (HIT) and what should be monitored for it when dosing UFH?

Back 38

Heparin-induced thrombocytopenia (HIT) - rare but can be fatal, severe platelet fall (>50%) in 7-10 days. WOOOOORRRY about this one! Platelets bind together and can form clots. MOSTLY FATAL

Front 39

What is monitored while patient is on UFH?

Back 39

aPTT
CBC - HgB, Hct, Platelets

Front 40

Is UFH reversible or Irreversible?

Back 40

Reversible in emergency

Front 41

What population is UFH the DOC for?

Back 41

Drug of choice in pregnancy & lactation

Agent of choice for kids

Front 42

Why can UFH be used in pregnacny?

Back 42

Large MW -->really big and is good because wont cross the placenta
Can use in 2nd and 1st trimester
Caution in last trimester (bleeding)

Front 43

What kind of patients should UFH not be used in?

Back 43

Potential for accumulation in renal impairment (and elderly). Small effect, related to enematic degradation maybe

Front 44

LMWH has what kDa?

Back 44

4.2-6 kDa

Front 45

LMWH has what kind of sequence? Does it have a tail for ternary complex?

Back 45

Contain the unique pentasaccharide sequence
May or may not have tail for ternary complex (~50%)

Front 46

LMWH binds to what factors?

Back 46

Still bind to antithrombin 3 and 10a

Activity tends to be more with 10a

Front 47

LMWH combines with ___ and ___ activity?

Back 47

Combines with ATIII and potentiates activity

Front 48

How long is the LMWH tail? What does it have most activity on?

Back 48

Tail is not long so it cant form the long complex

Most activty against 10a

Front 49

What kind of bioavailabulity does LMWH have?

Back 49

Bioavailability = >90d% when given SC (good) don’t have to use IV
Less protein binding

Front 50

When is the Peak effect and Half-life of LMWH?

Back 50

Peak effect = 3-5 hours

Half-life = 1.5-3 hours

Front 51

How is LMWH eliminated?

Back 51

Renal elimination (all renally eliminated)

Front 52

What kind of patients should it be avoided in?

Back 52

Important in patients with renal disease

Front 53

How is LMWH dosed?

Back 53

Fixed, weight based dosing (ABW)

Front 54

How is Enoxaparin dosed?

Back 54

Enoxaparin – mg : 1mg/kg a day

Front 55

How is TInazaprin and Dalteparin dosed?

Back 55

units

Front 56

How often is LMWH SQ injection dosed? What patient instructions should be given for it?

Back 56

Alternate sides q12 or q24, can really get subtermal hematoma, and ig bruising in the abs. can hurt a little bit too
Q12h - Q24h

Front 57

Caution using LMWH with which population? what should you monitor?

Back 57

Caution in obese, renal impairment still monitor more specifically with 10a levels

Front 58

When giving LMWH, all patientsshould monitor what?

Back 58

CBC for bleeding and SCr for renal impairment

Front 59

What is #1 adverse event of LMWH?

Back 59

bleeding

Front 60

What are adverse effects of LMWH?

Back 60

Bleeding is #1 adverse event

Bruising at injection site

Thrombocytopenia
HIT is rare but possible

Front 61

Is LMWH reversible or irreversible?

Back 61

Reversal = protamine (sort of, binds 50 % of the time)
Shorter chains on LMWH
60-70% neutralization

Front 62

What does LMWH have drug interactions with?

Back 62

anticoagulants/anitplatelets

Front 63

When should you not give LMWH?

Back 63

Cr clearance less than 30 ml/min

Front 64

What population can it be used in?

Back 64

Safe for use in pregnancy (do not cross placenta)

Kids:
Safe for use but monitor anti-Xa levels

Front 65

Factor Xa Inhibitors has what kind of sequence?

Back 65

Synthetic pentasaccharide sequence of UFH (fondaparinux)

Front 66

Factor Xa Inhibitors ____ binds to ____and potentiates action on factor ___?

Back 66

Reversibly binds to ATIII and potentiates action on fXa

Front 67

Factor Xa Inhibitors are Synthetic small molecular inhibitors of fXa. Which drugs are these specifically?

Back 67

(rivaroxaban, apixaban)  new oral agents

Front 68

How are Factor Xa Inhibitors available?

Back 68

Available as IV (fondaparinux) and PO forms (rivaroxaban, apixaban)

Front 69

Where does Factor Xa Inhibitors bind to? what doesn't it work on?

Back 69

Binds to antithrombin 3 and action on Xa. Does not work on thrombin

Front 70

(fondaparinux) only works on which factors? What doesn't it have an effect on?

Back 70

only works on 10-10a not to anthithrombin 3 and doesn't have any effect on thrombin

Front 71

Xa Inhibitors directly inhibits what?

Back 71

inhibit antithrombin binding to 10a

Front 72

Fondaparinux has what kind form, F(%), t 1/2 (hrs), elimination, dosing?

Back 72

SC
100
17-21
Renal
Daily

Front 73

rivaroxaban has what kind form, F(%), t 1/2 (hrs), elimination, dosing?

Back 73

PO
80-100
7-11
67% renal
Daily or BID

Front 74

apixaban has what kind form, F(%), t 1/2 (hrs), elimination, dosing?

Back 74

PO
66
8-25
25% renal
Bid

Front 75

How is XA inhibitors dosed? Which drug has an exception for this?

Back 75

Fixed daily dosing for all patients (fonaparaninox unless <50kg)

Front 76

What is monitored for XA inhibitor?

Back 76

CBC, SCr, anti-Xa levels (though it shouldn’t need it)
LFTs (liver function tests with rivaroxaban and apixaban)

Front 77

IS XA inhibitor reversible or irreversible?

Back 77

no reversal agent

Front 78

What are SE for XA inhibitors?

Back 78

Bleeding (no reversal agent) No paratimine
No risk for HIT--> very good thing

Front 79

What are special poplations for XA inhibitors

Back 79

Renal elimination-->
All Category B, but limited data

Front 80

What are 5 possible drug interactions with Rivaroxaban?

Back 80

Macrolides (↑ levels)
Diltiazem/Verapamil (↑ levels) increase can lead to bleeding
Azole antifungals (↑ levels)
Protease inhibitors (↑ levels)
p-glycoprotein inducers (↓ levels

Front 81

Explain the interaction with P-glycoprotein inducers and rivaroxaban?

Back 81

influx transports, transports molecules outside the blood brain barrier and GI tract. Riboroxaban depends on p-glycoprotein. Decrease levels of rivaroxaban

Front 82

What kind of metabolism does apixaban and rivaroxaban have?

Back 82

cyp3A4 metabolism

Front 83

What 2 drug interaction does Apixaban have?

Back 83

Macrolides (↑ levels)
Diltiazem/Verapamil (↑ levels)

Front 84

What interactions does fondaparinux have?

Back 84

none

Front 85

When Direct thrombin inhibitors are compared to UFH or LMWH, is it more or less predictable anticoag?

Back 85

more

Front 86

Where does direct thrombin inhibitors bind to?

Back 86

Bind directly to catalytic site (± fibrin binding site) of Thrombin

Front 87

What are 5 direct thrombin inhibitors

Back 87

Argatroban-2nd oldest trug
Bivalirudin
Lepirudin
Desirudin newer one
Dabigatran oral form and newest one

Front 88

Which direct thrombin inhibitors bind to both sites?

Back 88

Lepirudin and bialirudin

Front 89

Which direct thrombin inhibitors bind to one site?

Back 89

Argatroban
Dabigatran

Front 90

What is the route, monitoring parameters, clearance and half life for argatroben?

Back 90

IV
aPTT, ACT
Liver
30-60 min

Front 91

What is the route, monitoring parameters, clearance and half life for Bivalirudin?

Back 91

IV
aPPT, ACT
Proteolytic enzymes, Renal
25 min

Front 92

What is the route, monitoring parameters, clearance and half life for Lepirudin?

Back 92

IV,SC
aPPT
Renal
~60 min

Front 93

What is the route, monitoring parameters, clearance and half life for Desirudin?

Back 93

IV,SC
aPPT
Renal
~2 hrs

Front 94

What is the route, monitoring parameters, clearance and half life for Dabigatran?

Back 94

PO
NONE
Renal
12-17 hrs

Front 95

What kind of monitoring is needed with all Direct thrombin inhibitors? What is specific for Argatroban?

Back 95

all agents require CBC and SCR/ CrCL

Argatroban requires LFTS

Front 96

What is the most common AE for DTI?

Back 96

Bleeding?

Front 97

IS there a reversing agent for DTI

Back 97

NO

Front 98

What is most common SE with Dabigatran?

Back 98

GI upset and GI bleeding (happens from upset) are most common (>10%)

Front 99

What drug interactions are common with Dabigatran?

Back 99

p-glycoprotein inducers (rifampin, St. John’s Wort) and inhibitors (amiodarone, cyclosporine, verapamil, ketoconazole, quinidine)

Front 100

What does Warfarin inhibit?

Back 100

Inhibits vitamin-K reductase in liver. Inhibits very speficific enzymes that depend on vit k

Front 101

What are the VIT K dependent factors?

Back 101

prothrombin (factor 2)
7
9
10
Protein C and Protein S

Front 102

What are the half lives for prothrombin (factor 2)
7
9
10
Protein C and Protein S

Back 102

60-100 hrs
6-8 hrs
20-30 hrs
24-40 hrs
8-10 hrs
40-60 hrs

Front 103

How long does it take for warfarin to reach maximal effect?

Back 103

Maximal effect is 5 days (3-500 hrs)

Front 104

What do you monitor in patients with Warfarin?

Back 104

Check INR every day

Front 105

What kind of mixture is warfarin? Which is more potent?

Back 105

Racemic mixture of S and R isomers
S is 2-5x more potent

Front 106

Where is warfarin absorbed? What is its peak concentration?

Back 106

Rapidly absorbed from GI tract - peak concentration in 90 minutes

Front 107

What enzymes is warfarin metaboloized by?

Back 107

Metabolism by liver enzymes 1A2, 2C9, 3A4 predominantly. Rapidly absorbed

Front 108

IS warfarin the same dose for everyone?

Back 108

No
VKOR and c29 genetic variability

Front 109

What do you use to monitor warfarin?

Back 109

International Normalized Ratio (INR)

Front 110

What are all the components that we used to monitor warfarin?

Back 110

CBC bleeding
LFTs liver function because its metabolized there
Diet (table 21-17) Monitor vitamin k levels. If they take a lot, warfarin is not going to work and INR is going to go down

Front 111

What are AEs of Warfarin?

Back 111

Bleeding
Purple Toe syndrome
Warfarin Induced skin necrosis

Front 112

What is purple toe syndrome?

Back 112

necrotic toes, starting warfarin therapy)
Caused from warfarin inhibiting Protein C an S (natural anticoag) . By inhibiting this , it causes blood clot to toes

Front 113

what is Warfarin-induced skin necrosis

Back 113

mini thrombi in microvascular, looks like really dark bruises in legs and arms

Front 114

How do you manage bleeding with warfarin?

Back 114

Mildly-elevated INR (3.5-5.0)--> reduce dose or hold 1-2 doses

Can give vit K right away

Front 115

Does warfarin have a reversal agent?

IS it immediate?

Back 115

YES is INR is greater than 5-6-7
IV or PO vit K
Its not an immediate reversible

Front 116

What if a patient comes in with very serious bleeding with an INR of 10 on warfarin, what do you do?

Back 116

Give them vitamin K and fresh frozen plasma (all clotting factors are in this)

Front 117

What is the MOA of Aspirin?

Back 117

Irreversibly inhibits COX enzymes of arachidonic acid pathway and conversion to thromboxane A2 (TXA2)

Front 118

What does Aspirin inhibit?

Back 118

thromboxane A2

Front 119

How do you dose aspirin?

Back 119

1 qd for prophylaxis
Mg dose depends on indication
81-162 mg for prevention of MI/stroke (most of the time)
325mg for prevention of MI/stroke after event (for a period of time)
325-650mg q4h for pain/fever

Front 120

What do AE fo you monitor aspirin for?

Back 120

Monitoring:
Bleeding (obviously)

Front 121

Aspirin takes how long for platelet inhibition?
Metabolized where?
Half-life?

Back 121

Platelet inhibition = 1-7.5 minutes
Metabolized by liver
Half-life = 6 hours

Front 122

What are SE of Aspirin?

Back 122

GI upset and ulcer
Bleeding
Bronchospasm

Front 123

What is a true aspiring allergy?

Back 123

bronchospasm or asthma, nasal polyps, anaphylaxis

Front 124

What do you do if a patient has an aspirin allergy?

Back 124

Check to see if it a true allergy or is it a stomach ache?

Front 125

What populations is should aspirin not be used in?

Back 125

Do not use in pregnancy (category D)
Children - ≥12 years ok to use (try something else first); Kawasaki’s disease
Liver impairment (or alcohol use)

Front 126

Why dont you use aspirin in pregnancy?

Back 126

In the AA pathway thromboxane a 2 is produced, prostaglandins are produced. Prostaglandins in pregnancy can speed up labor—DON’T USE

Front 127

What are 3 Thienopyridines (brand/generic) drug

Back 127

ticlopidine (Ticlid®)
clopidogrel (Plavix®)
prasugrel (Effient®)

Front 128

What is MOA of Thienopyridines

Back 128

Irreversibly inhibit platelets at ADP Y2 receptor (P2Y12 receptor)

Front 129

What needs to happen the thinepyridines before they are used?

Back 129

Since they are all prodrugs they need to be activated by liver enzyme before they work

Front 130

Clopidgrel has what liver enzymes associated with it?

Back 130

2C19 (major), 3A4, 2B6, 1A2

Front 131

Prasugrel has what liver enzyme associated with it?

Back 131

3A4

Front 132

Where are Thineopyridines metabolized?

Back 132

liver

Front 133

What are the half lifes for ticlopidine, clodipgrel and prasugrel

Back 133

ticlopidine = 4-5 days
clopidogrel = 6 hours
prasugrel = 8 hours
Remember the irreversible inhibition of platelets!!

Front 134

What is the Dosing for clopidogrel?

Back 134

300-600mg load, then 75mg daily for clopidogrel

Front 135

What is the dosing for prasugrel?

Back 135

60mg load, then 10mg daily for prasugrel

Front 136

What are the common SE of Theinopyridines and aspirin?

Back 136

Bleeding (very common)
GI upset and bleeding (especially with aspirin)

Front 137

Prasugrel has what specific SE?

Back 137

Hypertension and hyperlipidemia (prasugrel)

Front 138

Theinopyridines interact with what?

Back 138

SSRIs/SNRIs

Front 139

What is a major interaction with clopiogrel?

Back 139

PPIs (esp. omeprazole) with clopidogrel

Front 140

What is the MOA if Ticagrelor (Brilinta)?

Back 140

Reversibly binds and inhibits P2Y12 receptor and ADP-induced platelet activation

Front 141

What patients is Ticagrelor used in?

Back 141

For acute coronary syndrome with or without PCI

Front 142

Ticagrelor has increased bioavaliability with ___

Back 142

food

Front 143

Ticagrelor is metabolized by what?
What kind of onset?
half-life?

Back 143

Metabolized by 3A4
Onset = 2 hours very quick
Half-life = 7 hours (active metabolite = 9 hours)

Front 144

What kind of dosing the ticagrelor have?

Back 144

Requires loading dose = 180mg
90mg BID ( a little different)

Front 145

What are SE with ticagrelor?

Back 145

Bleeding (esp. with other anticoags/platelets)
Common: headache, increase SCr, dyspnea/cough
Serious: bradycardia/pauses, AF

Front 146

What are 3 Glycoprotein IIb/IIIa Inhibitors (brand/generic) drugs?

Back 146

eptifibatide (Integrilin®)
abciximab (ReoPro®)
tirofiban (Aggrastat®)

Front 147

what is MOA of Glycoprotein IIb/IIIa Inhibitors

Back 147

Bind to GPIIb/IIIa receptor to prevent fibrin crosslinking and platelet aggregation
Final step

Front 148

Eptifibatide (Integrilin®) is what kind of molecule?
Bolus and Infusion dosing?
How eliminatated?
What kind of platelet binding?
What % of bleeding risk?

Back 148

peptide

Bolus:
180mcg/kg x 2
Infusion:
2mcg/kg/min x 18-24 hrs

Renal
CrCl <50mL/min:
1mcg/kg/min

reversible
9-11%

Front 149

Abciximab(ReoPro®) is what kind of molecule?
Bolus and Infusion dosing?
How eliminatated?
What kind of platelet binding?
What % of bleeding risk?

Back 149

Monoclonal Antibody
Bolus:
0.25mg/kg

Infusion:
0.125mg/kg/hr x 12 hrs

Plasma

irreversible
14%

Front 150

Tirofiban (Aggrastat®)
is what kind of molecule?
Bolus and Infusion dosing?
How eliminatated?
What kind of platelet binding?
What % of bleeding risk?

Back 150

non-peptide
Bolus:
0.4mcg/kg/min x 30min
Infusion:
0.1mcg/kg/min up to 4 days

Renal
Bolus:
CrCl < 30mL/min:
0.2mcg/kg/min
Infusion:
0.05mcg/kg/min

Reversible
10-12%

Front 151

What are 5 thrombolytic drugs?

Back 151

Streptokinase (Streptase®)
Urokinase (Abbokinase®)  human urine it was used in
alteplase (Activase®; rtPA)
reteplase (Retevase®)
tenecteplase (TNKase®)

Front 152

What is the thrombolytic mechanism?

Back 152

Plaque form- plaq rupture txa, tf and tpa is released, thrombus forms, plaminiagen bound to thrombus, tpa binds to plasminagen to it and activates it and converts it to plasmin, then plasmin degrades the fibrin strands and degrades the thrombus.

Front 153

What is the bolus and infusion Dose and bleeding % of Alteplase (Activase®)?

Back 153

Bolus: 15mg
Infusion:
0.75mg/kg over 30 minutes, then
0.5mg/kg over 60 minutes

15%

Front 154

What is the bolus Dose and bleeding % of Reteplase
(Retavase®)

Back 154

Bolus: 10mg over 2 minutes (x2)
*Given 30 min apart

15.5%

Front 155

What is the bolus Dose and bleeding % of Tenecteplase
(TNKase)

Back 155

Bolus (over 5 sec):
<60kg = 30mg
60-69.9kg = 35mg
70-79.9kg = 40mg
80-89.9kg = 45mg
≥90kg = 50mg

22%

Front 156

What are thrombolytics used in?

Back 156

Used in STEMI, PE, ischemic stroke

Front 157

*********
What are contraindications of thrombolytics?

Back 157

Any history of intracranial hemorrhage
Head/facial trauma w/in 3 months
Uncontrolled HTN
Ischemic stroke w/in 3 months

Front 158

What are SE of thrombolytics?

Back 158

Bleeding (everywhere)
GI hemorrhage
Anaphylaxis