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VTE, AFib, and Arrythmia > Pharmacotherapy of Anticoagulants for VTE > Flashcards

Pharmacotherapy of Anticoagulants for VTE Flashcards

1
Q

The MOA of heparin (UFH) is…

A

Catalyzation of antithrombin, which inactivates factor 2a, 9a, 10a, 11a, and 12a

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2
Q

Heparin affects this lab value…

A

aPTT - prolongation

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3
Q

Heparin has unpredictable PK and PD, because…

A

It binds to other cells and other plasma proteins

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4
Q

Onset of effect with heparin is…

A

Immediate with IV
30-60 minutes with Subcut

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5
Q

Duration of effect with heparin is…

Half-life? How often is it given?

A

Half-life of 1-2 hours;
IV is given continuously, SC is given q8h

Cannot have anticoag free period during clot treatment

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6
Q

Some indications that may warrant caution/monitoring with heparin use include…

A

Active bleeding, or conditions that increase risk of bleeding
Injuries + operations to brain, spinal cord, eyes/ears
Severe thrombocytopenia
Prior occurrence of HIT

No absolute CI since PE mortality is high

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7
Q

Dosing of heparin differs based on…

A

Body weight
Use for prophylaxis or treatment, IV or SC

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8
Q

Response to heparin treatment dose may be variable because of…

A

Narrow therapeutic window

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9
Q

Heparin will usually be given for ____ days, simultaneously with _____

A

<7 days, with warfarin (THIS was before DOAC’s existed)

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10
Q

Common adverse effects resulting from heparin include…

A

Minor bleeds
If SC, injection site reactions
Transient, mild liver enzyme increase

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11
Q

Serious adverse effects that may result from heparin include…

A

Major bleeds
Heparin induced thrombocytopenia (HIT)

Hyperkalemia, skin necrosis, BMD decrease with LONG duration of usage

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12
Q

In the case of a major bleed with heparin usage, what could be given as an antidote?

A

IV protamine sulfate

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13
Q

What kind of reaction is HIT? What happens to the platelets?

A

Immune-mediated platelet aggregation reaction - platelets activate and stick together

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14
Q

HIT is a severe risk, because it results in increase to…

A

Both thrombotic AND bleed risk

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15
Q

Onset of HIT usually occurs ____ after heparin initiation

A

5-10 days

May depend on prior heparin exposure

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16
Q

A good way to judge likelihood of HIT is…

A

The 4Ts score for HIT

Criteria that tells probability of HIT

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17
Q

The 4Ts criteria of measuring HIT likelihood are…

A

Degree of thrombocytopenia
Timing of decrease in platelet count
Thrombosis
Other causes of thrombocytopenia

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18
Q

If HIT occurs, the following needs to be done…

A

Discontinuation of ALL sources of heparin
Begin alternate anticoagulation

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19
Q

Alternate anticoagulation when HIT occurs include…

A

DOAC’s in stable patients with medium bleed risk - rivaroxaban preferred
Argatroban, fondaparinux, danaparoid, bivalirudin

Warfarin initially unsuitable, but can transition to once platelets OK

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20
Q

Drug interactions to note with heparin usage include…

A

Anything that may increase anti-coagulation or incrase thrombotic risk

Antiplatelets, NSAID’s, estrogens, herbals

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21
Q

This lab value shows the effectiveness of heparin VTE treatment:

Used for dosage adjustments, so is MANDATORY

A

aPTT for VTE treatment - use of validated nomograms

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22
Q

The following should be monitored during heparin treatment:

A

Platelet count - baseline if possible, and every other day
Hgb and hematocrit
Potassium if high risk of hyperkalemia

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23
Q

The low-molecular weight heparin (LMWH) most commonly used in SHA is…

A

Tinzaparin

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24
Q

Which LMWH is best to use?

A

ALL appear equal, clinically in safety and efficacy - just not interchangeable due to different dosing regimens

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25
Q

Enoxaparin is unique in that it can be used…

A

In acute ACS

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26
Q

The MOA of a LMWH is…

A

Similar to heparin, but higher affinity for 10a

Can affect aPTT, and can be monitored with Anti-10a if needed

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27
Q

A benefit of LMWH compared to heparin in terms of PK is…

A

More predictable PK properties, so it can be administered in fixed doses without need for dose adjustment based on lab monitoring

CONVENIENCE

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28
Q

Cautions with LMWH include…

A

Identical to heparin

Again, not absolute CI, except for previous occurrence of HIT; PE severe

Active bleeding, or conditions that may increase bleed risk
Injuries/operations to brain, spinal cord, eyes/ears
Severe thrombocytopenia

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29
Q

LMWH’s are given…

Route of admin?

A

Subcut

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30
Q

Dosing of tinzaparin for VTE prophylaxis is…

A

75 units/kg

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31
Q

Dosing of tinzaparin for VTE treatment is…

A

175 units/kg

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32
Q

In impaired kidney function, tinzaparin is okay to use down to…

CrCl?

A

20mL/min for prophylaxis
~25-30 mL/min for treatment

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33
Q

Can we dose adjust tinzaparin in renal impairment?

A

No - we CAN or CANNOT use.

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34
Q

Does tinzaparin dosing change in obese patients?

A

Yes, dose increases; >30 000 units subcut daily and above

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35
Q

Does tinzaparin dosing change in pregnancy?

A

Yes - metabolism of LMWH is altered throughout the course of pregnancy, especially in the 3rd trimester

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36
Q

Onset of effect of tinzaparin is…

When is peak?

A

~1 hour - peak anti-coagulation response in 3-5 hours

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37
Q

The adverse profile of LMWH’s compared to UFH is…

A

Similar, but much lower incidence of common AE’s, as well as MUCH lower risk of HIT

Drug interactions are also similar, just watch antiplatelets, anticoags

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37
Q

Duration of effect of tinzaparin is…

A

12-24 hours of anti-10a activity; half-life of 3-6 hours

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38
Q

Do we need to monitor for LMWH efficacy? If so, how?

A

Monitoring is not indicated, unless patient is obese, pregnant, or has renal issues. Cannot use aPTT, so we need to use Anti-10a, 4 hours post-dose

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39
Q

For safety monitoring of LMWH, what should be measured?

A

Platelet count; baseline, and every other day (if 4+ days)
Hgb and hematocrit, baseline and q3d
Potassium if high risk of hyperkalemia
Renal function

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40
Q

Fondaparinux and danaparoid share the same MOA by…

A

Inhibiting Factor Xa

Similar to LMWH

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41
Q

Argatroban’s MOA is to…

A

Directly inhibit thrombin (II)

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42
Q

Advantages of fondaparinux compared to LMWH include…

Safety? Adherence?

A

No cases of HIT reported, may be superior in preventing recurrent events
Fixed dosing, studied in obesity
No monitoring

43
Q

Advantages of danaparoid and argatroban compared to LMWH include…

Safety? Adhrerence?

A

Specifically studied to treat HIT
No dose adjustments needed in obesity
CAN be used in severe renal impairment

44
Q

Some disadvantages of using fondaparinux compared to LMWH include…

Safety? PK?

A

Possible increase in major bleeds with high doses
No antidote
Longer half-life
Can only use up to CrCl of 30 mL/min

45
Q

Some disadvantages of using danaparoid or argatroban instead of LMWH include…

Safety?

A

No antidone available
Limited pregnancy experience

46
Q

Warfarin MOA is…

A

Vitamin K antagonist - interferes with production of clotting factors, dependant on vitamin K

47
Q

What clotting factors are dependant on vitamin K?

A

10, 9, 7, 2
Protein C&S

48
Q

Onset of effect of warfarin is important to note, because…

Also how long?

A

It is not immediate since vitamin K clotting factors need to be cleared from circulation

Takes 2-7 days (avg 3-5)

Offset will also take a similar time

49
Q

While on warfarin, any changes in dose, diet, or drug-interactions will have a ____ effect

A

Delayed

Remember that vitamin K clotting factors take 2-7 days to clear

50
Q

CI’s to warfarin usage include…

A

Pregnancy
High risk of bleed where benefit of anticoagulation > risk of bleeding
Previous skin reaction to warfarin

High risk = active bleed, recent surgery, inadequate lab facilities, etc

51
Q

When initiating warfarin dosing, the following needs to be considered:

A

Age/Frailty
Risk of bleeding
Urgency to reach therapeutic INR
Medications/Drug-interactions

52
Q

A good method to adjust warfarin dosing is…

A

To follow validated nomograms

53
Q

Lots of other factors can influence INR, such as…

A

Liver disease
Diet; Vitamin K
Drug interactions
Acute illnesses, physical activity

54
Q

When dealing with sub-therapeutic or supra-therapeutic INR’s what is the thought process?

A

Determine indication and target INR - any symptoms of high/low INR?
Is there a TREND? Time since last INR?
Any risk of having issues develop?
Transient or permanent cause?

55
Q

What are symptoms of high or low INR?

A

High - signs of bleeding
Low - signs of stroke or VTE

56
Q

If a patient has no physical symptoms with a high/low INR, when is the patient at risk of having issues develop

A

Pt. risk factors: Antiplatelet usage, fall risk, frailty, bleed history
Extreme highs and lows in INR

Extremely high warrants vitamin K; extremely low may warrant LMWH

57
Q

If a sub/supra-therapeutic INR is from a transient cause (foods, acute drug usage), what should be done?

A

Consider dose correction. and increase frequency of INR monitoring

58
Q

If a sub/supra-therapeutic INR is from a permanent cause (addition of chronic drug, or medical condition), what should be done?

A

Weekly dose change, and increase INR monitoring

59
Q

When would we have to bridge TO warfarin therapy?

If we are using warfarin and not other DOAC

A

During initial treatment of VTE
Prevention of VTE after high-risk procedure
Patient at hish risk of VTE undergoing surgery

Essentially higher risk for clots

60
Q

A downside of bridging to warfarin therapy is…

Consider need for rapid anticoagulation

A

Delayed onset, and may be prothrombotic when started

61
Q

When briding to warfarin is needed, the following should be done:

A

Initiate warfarin and UFH/LMWH simultaneously

Overlap for at least 5 days AND until INR is 2+ for 2 days

62
Q

When bridging OFF warfarin therapy, we must assess…

Risks of?

A

Risk of thrombosis for stopping anticoagulation, vs. bleed risk for continuing (during surgery)

63
Q

When bridging off warfarin therapy, the following steps are recommended:

Steps involved? INR levels involved? Time management?

A

Stop warfarin 3-5 days prior to surgery, and wait until INR drops <1.5

Begin UFH or LMWH once INR <2, stop UFH 4-5 hours pre surgery and LMWH 24 hours pre surgery

Resume UFH or LMWH 24+ hours after surgery with warfarin

64
Q

Common adverse effects of warfarin include…

A

Minor bleeds
Abdominal cramps
Diarrhea + Nausea
Skin reactions/hives are rare but not serious

Minor bleeds = bruises, cuts, gums, nosebleeds, etc.

65
Q

Serious adverse effects of warfarin include…

A

Major bleeds
Purple toe syndrome
Skin necrosis

Major bleeds = blood where blood should not be

66
Q

Drug interactions with warfarin work via two mechanisms:

A

Change in INR due to enzyme induction/inhibition
Synergistic increase in bleeding risk without affecting INR

67
Q

8 major classes of interacting drugs with warfarin are…

All but one start with A

A

Antibiotics
Antifungals
Antidepressants
Antiplatelets
Anti-inflammatories
Acetaminophen
Alternative remedies (herbals)
Corticosteroids

Any 2C9 inhibitor/inducer will have a strong effect

68
Q

Addition of acute drugs onto warfarin therapy is most risky, because…

A

Can be difficult to manage lots of fluctuations compared to chronic dosing

69
Q

When managing warfarin DI’s, the best thing to do is…

A

Check INR again in 4-6 days and adjust dose in response for those that can be monitored

Balance risk of bleed/clot with benefit of therapy for those that cannot be monitored (ex: NSAID, antiplatelet, hormones)

Empiric dose adjustment to warfarin is more risk and unpredictable - don’t do unless its well documented

70
Q

How often should INR be monitored?

A

Day 3&5
then twice weekly F1W
then weekly until stable for 2 weeks. Then every 2 weeks until stable for a month
then monthly.

If really stable, can extend up to Q3months

Check in 4-6 days after dose changes, or other issues

71
Q

It is important to inform patients to monitor for signs of major bleeds, such as…

A

Bright red blood in stool
Darkened, foul-smelling stools
“Coffee ground” vomit
Cuts that do not clot within 5 minutes

72
Q

The best piece of advice to give to patients about warfarin therapy is…

A

Do not start any new meds/OTC’s/Herbals, or make drastic changes in diet without talking to pharmacist +/- physician

73
Q

In case of a bleed, or extremely elevated INR (>10), what can be given as an antidote?

A

Vitamin K

2.5 - 5mg orally will reduce INR in 24-48 hours

74
Q

If a serious bleed occurs with warfarin regardless of INR, what should be done?

A

HOLD warfarin
GIVE vitamin K 5-10mg IV q12h
Give factor IV prothrombin complex or FFP

75
Q

The four DOAC’s are…

A

Rivaroxaban
Apixaban
Edoxaban
Dabigatran

76
Q

MOA of DOAC’s is…

A

Rivaroxaban, apixaban, and edoxaban inhibit Factor 10a
Dabigatran directly inhibits thrombin

10a is Xa which is in the name

77
Q

Onset of effect for DOAC’s is…

A

Reaching peak anti-coagulation in about 2 hours

Makes bridging from different anti-coags easy, but makes adherence key

78
Q

Duration of effect for DOAC’s relies on their half-life, which is…

A

Rivaroxaban: 9h
Apixaban: 8-14h
Edoxaban: 14h
Dabigatran: 13h, up to 18h with renal impairment

Duration is important for when to d/c prior to surgery

79
Q

When do DOAC’s need to be avoided in renal impairment?

A

Dabigatran <30 mL/min
Apixaban, edoxaban, and rivaroxaban <15 mL/min

80
Q

Can DOAC’s be used in hepatic disease?

A

No, except for dabigatran which is cautioned

81
Q

CI of ALL DOAC’s include:

A

Active or high risk of bleeding
Pregnancy + lactation

82
Q

Which enzymes are involved in metabolism of DOAC’s?

A

D-GP and 3A4
Both inducers and inhibitors

Therefore DOAC’s have a lot of DI’s

Weak/moderate inhibitors may not be significant enough

83
Q

Which DOAC’s may have less drug interactions?

A

Dabigatran and edoxaban

Not affected by 3A4 inhibitor + inducers

84
Q

Dabigatran has unique DI in that it is affected by anything that _____

A

Raises pH

PPI’s

85
Q

These DOAC’s are usually dosed BID:

A

Apixaban, Dabigatran,

86
Q

These DOAC’s are usually dosed once daily

A

Edoxaban, rivaroxaban

87
Q

Dose of rivaroxaban for VTE prevention, after TKR/THR, is…

TKR = total knee replacement; THR = total hip replacement

A

10mg once daily; 35 days for hip, 14 days for knee

88
Q

Dose of rivaroxaban for VTE treatment is…

A

15mg BID cc for 3 weeks, then 20 mg once daily for 3-6 months

WITH FOOD

89
Q

Dose of rivaroxaban for prevention of recurrent VTE is…

A

10-20mg daily cc, 6 months after treatment dose

WITH FOOD

90
Q

These two DOAC’s need bridging for VTE treatment:

A

Dabigatran and edoxaban

91
Q

Dose of apixaban for VTE prevention after TKR/THR is…

A

2.5 mg BID; 35 days for hip and 14 days for knee

92
Q

Dose of apixaban for VTE treatment is…

A

10mg BID for 7 days, then 5mg BID for 3-6 months

93
Q

Dose of apixaban for recurrent VTE prevention is…

A

2.5mg BID, 6 months after treatment dose

94
Q

Dose of dabigatran for VTE prevention after TKR/THR is…

Differs on age!

A

110mg stat, then 220mg daily; 35 days for hip and 14 days for knee

Reduced to 150mg once daily if 75+

95
Q

Dose of dabigatran for treatment of VTE is…

This is special

A

5-10 days of SC anti-coag, then prevention dose of 150mg BID (or 110mg BID if bleeding risk is high)

96
Q

Dose of dabigatran for preventing recurrent VTE is…

A

150mg BID; 110mg BID if bleeding risk is high

97
Q

Edoxaban dosing for treatment of VTE/prevention of recurrent VTE is…

A

After bridging for 5-10 days with SC anti-coag, 60mg once daily

30mg if under 60kg

98
Q

DOAC’s relationship with obesity is…

Which DOAC’s should be avoided?

A

Can use, but potential unknown risks… Avoid dabigatran and edoxaban, or just use warfarin

99
Q

Common side effects of DOAC’s include…

A

Minor bleeding (similar to warfarin)
GI upset, dyspepsia, diarrhea, constipation
Itch

100
Q

Serious side effects of DOAC’s include…

A

Major bleeds

But mostly better, or same risk as warfarin

101
Q

What should we monitor with DOAC usage?

ABCDE

A

A: Adherence
B: Bleeding
C: CrCl (baseline, and more frequent depending on fx)
D: Drug interactions
E: Exam for LFT’s, plasma, etc.

No really direct monitoring like warfarin and INR

102
Q

How long should anticoagulant therapy be if used for VTE provoked by a transient risk factor

Meaning that we know what caused it

A

3 months, 6 months if symptoms persist or very large DVT/PE

Or just low risk of bleed

103
Q

How long should anticoagulant therapy be, if used for unprovoked VTE?

Differs based on bleed risk

A

Minimum of 3 months, then reassess:
Low/moderate bleed risk: indefinite with periodic reviews
High bleed risk: 3 months

Having a second unprovoked VTE strongly suggests indefinite therapy

104
Q

How long should anticoagulant therapy be, if used for VTE associated with ongoing risk factors?

A

Indefinitely with periodic reviews, or as long as the risk factor persists

105
Q

How long should anticoagulant therapy be, if used for cancer associated VTE?

A

Minimum of 3 months, then reassess and continue if active therapy/continuing to receive anticancer therapy

VTE, AFib, and Arrythmia (2 decks)

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