Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

344 final > VTE Part 2 > Flashcards

VTE Part 2 Flashcards

1
Q

Rivaroxaban (Xarelto™)

A

• Oral tablet
Metabolized by CYP 3A4, 2J2
& CYP-independent ways Larger doses (15mg & 20mg) should be taken with food / largest meal of the day (if not only 2/3 absorbed)
MOA: Competitive, direct (antithrombin independent) Factor-Xa Inhibitor (both free and clot-associated Xa)
Side Effects:
– Bleeding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Rivaroxaban-drug interactions?

A

– Strong inhibitors of both CYP
450 3A4 and P-glycoprotein
– Caution with Inducers
– Increase risk of bleeding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Rivaroxaban Dosing

A

Treatment of acute VTE* 15mg BID x 3 weeks, then
20mg daily
(take with food)
As per VTE assessment, 3 months to lifelong

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Apixaban (Eliquis™)

A

Oral tablet
Metabolized by CYP
3A4/5, minor from 1A2,
2C8, 2C9, 2C19, 2J2

MOA: Competitive, direct
(antithrombin
independent) Factor-Xa
Inhibitor (both free and
clot-associated Xa)
• Side Effects:
– Bleeding
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Apixaban-drug interactions

A

– Strong inhibitors of both
CYP 450 3A4 and Pglycoprotein
– Caution with Inducers
– Increase risk of bleeding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Apixaban Dosing

A

Treatment of acute
VTE*
10mg BID x 7 days, then 5mg BID
As per VTE assessment, 3 months to lifelong†

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Edoxaban (Lixiana™)

A 
• Oral tablet • Peaks in 1-2 hours 
MOA: Competitive, direct
(antithrombin independent)
Factor-Xa Inhibitor (both
free and clot-associated Xa)
• Side Effects:
– Bleeding
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Edoxaban Dosing

A 
Treatment of
acute VTE*
After 5-10 days treatment with a
parenteral anticoagulant, edoxaban
dosing as per AF
As per VTE assessment, 3
months to lifelong

AF: 60 mg once daily if CrCL >50
30mg once daily if CrCL 30-50, body wt <60kg

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Edoxaban -drug interactions?

A

see table 49

Drug Interactions:
– Strong inhibitors or inducers
of P-glycoprotein
– Increase risk of bleeding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

DOAC Dosing for the Acute Treatment of VTE

A

Apixaban
10 mg BID (1 week) –> 5 mg BID

Dabigatran
Parenteral Anticoagulant 5-10 Days -> 150 mg BID or 110 mg BID*

Edoxaban
Parenteral Anticoagulant 5-10 Days -> 60 mg daily or
30 mg daily

Rivaroxaban
15 mg BID (3 weeks) -> 20 mg QD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Which of the following is correct?
1. The D-dimer is helpful to rule out VTE if it is
positive
2. Dabigatran and Rivaroxaban require a parenteral
anticoagulant lead in for the acute treatment of
VTE
3. Both dabigatran and edoxaban are subject to
drug interactions with P-glycoprotien inhibition.
4. For apixaban, edoxaban and rivaroxaban,
routine PT/INR monitoring should occur as well
as the creatinine clearance.

A

3

we don’t do routing monitoring for any of them

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

DOAC: Contraindications

A

• Mechanical heart valves
• Active bleeding or risk of bleeding deemed too high
• Pregnancy or breastfeeding (no data)
• Moderate to severe hepatic impairment (limited, if any data)
• Drug Interactions:
– Dabigatran: strong P-gp inhibitors/inducers
– Edoxaban: strong P-gp inducers
– Rivaroxaban & Apixaban: strong inhibitors / inducers of both CYP 3A4 & P-gp
• Severe renal impairment cut offs:
– Dabigatran: CrCl < 30mL/min
– Apixaban: CrCl < 25 mL/min
– Rivaroxaban < 15 mL/min
– Edoxaban < 15 mL/min

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

DOAC impact on Coagulation Tests

see slide 52

A

ok

dont need routine coag monitoring

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Treatment Options for Acute VTE

Must Act Quickly

A 
Indirect Acting Anticoagulants
• Heparins (subcutaneous)
– Low molecular weight heparin
(LMWH) - subcutaneious
– Unfractionated heparin (UFH) –
intravenous or subcutaneous
• Fondaparinux (subcutaneous)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Initial – Long-Term Treatment Phase: Options

A

VTE Parenteral Anticoagulant (LMWH,
fondaparinux) + Warfarin to an INR of 2.0-
3.0, then warfarin (INR 2.0-3.0) alone
Overlap with parenteral agent at least 5 days or until
INRs > 2.0 for at least 2 days (whichever is longer)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Mechanisms of Action:

UFH, LMWH, Fondaparinux

A

• LMWH vs UFH – size of molecule
• Both contain pentasaccharide
sequence binding to antithrombin
→ accelerates interaction with Xa
• LMWH (smaller), primarily Xa
• UFH, larger, requires chain to wrap around factor II = thrombin hence both Xa and IIa
• Fondaparinux – synthetic pentasaccharide sequence
• ALL require antithrombin = not direct acting anticoagulants

small ones only impact Xa
unfractionated hep impacts Xa and IIa depending on size

inactivating thrombin and activated factor X (factor Xa) through an antithrombin (AT)-dependent mechanism.

17
Q

which one needs antithrombin?

A 
Direct Xa Inhibitors (PO):
Rivaroxaban, Apixaban
– Do not require
antithrombin
– Act directly on Factor Xa

• Direct IIa Inhibitor
(PO): Dabigatran
– Acts directly on
Factor IIa

18
Q

UFH dosing

A

Weight based, then guided
based on aPTT or anti-Xa

need to routinely monitor coag activity
not needed for LMWH and Fonda

19
Q

UFH for Initial VTE Treatment

• Place in Therapy:

A

– Situations wherein reversal of anticoagulant effect may be anticipated
(extensive clot, circulatory compromise=massive PE) → IV drip is typically used
– Renal dysfunction (CrCl < 20mL/min)

20
Q

Thrombolytic Therapy for PE

A

Lysis accelerates resolution of PE BUT increases risk of
major bleeding (harm outweighs benefit for majority)
- lots of intracranial hemorrhage
Reserved for those at greatest risk of dying from PE –
with “massive” PE or PE with cardiopulmonary
compromise

21
Q

LMWH: Coagulation Assessment?

A

only do it for uncertain dosing or• Anit-Xa Levels (akin to LMWH Levels –
pharmacodynamic effect)
– Recommend against routine monitoring of Anti-Xa
levels
– Anti-Xa levels have never been correlated with clinical outcomes tx failure
Consider assessing if potentially unsure of dosing:
• Extremes of weight
• Renal dysfunction
• Failure of therapy (clot or bleed)

22
Q

• Renal dysfunction
• Obesity
LMWH

Pre-filled syringes: operationally looking for syringe strength that best matches
weight; can round to higher strength (if high clot risk) or lower strength (if higher
bleed risk); ideal to stay within 10% of body weight dose

A 
• Renal dysfunction
– LMWH are primarily renally eliminated
• Enoxaparin >> dalteparin > tinzaparin
– <20 mL/min – use UFH
– 20-30 mL/min – tinzaparin
– > 30 mL/min –dalteparin, enoxaparin or tinzaparin

• Obesity
– Dosing based on total body weight (TBW) is recommended when using LMWH
– Don’t dose cap (contradicts Canadian product monographs)
– Will administer it Q12H (often so only one syringe is injected)
• Pretty much exclusively use pre-filled syringes

23
Q

Heparin Adverse Effects

A 
• Bleeding
– Less with LMWH vs UFH
– Protamine can be used to neutralize UFH, partially
neutralizes LMWH
• Osteoporosis
– Risk increases with duration of use
– Lower risk with LMWH vs UFH
• Hematoma at injection site
• Hypersensitivity
• Alopecia
• Heparin Induced Thrombocytopenia (HIT) ***
– UFH >>> LMWH
24
Q

Heparin-Induced Thrombocytopenia
which 2 types

More common in unfractionated hep than LMWH

A 
Type I
– Non-immune mediated
– Transient, mild thrombocytopenia
– Early onset (< 4 days)
– Reversible, asymptomatic
– Commonly seen, especially in the
post-operative patient
Type II
– Immunologic drug reaction
– Severe thrombocytopenia
– Late onset (day 5 –14) but can develop within 24hrs if heparin exposure in last 100 days
– Clotting disorder
– Life threatening

neoantigen tht is recognized by the FC receptor of the platelets and then we have intense platelet activation and then the platelets form clots.
They recruit their colleagues and release pro coagulate micro particles which further amplifies this and the end result is thrombosis, we see a dramatic drop in the platelets.

25
Q

HIT Type II:

Consequences, Monitoring & Diagnosis

A

Potential Consequences:
• Thrombotic complications occur in 20 –50% of patients
• Thrombosis may be arterial or venous
• Results in limb amputation in 10% of patients
• Fatal in 8 –20% of patients

Monitoring for:
• Platelet count typically falls below 150 X 109
/L, however decrease from baseline
platelets of 40-50% is hallmark
• With heparin administration, clinical signs/symptoms of:
• clot (venous or arterial)
• skin necrosis/lesions at injection site
• systemic reactions (fever/chills) after IV heparin bolus

Diagnosis:
• Based upon clinical sequlea (above) plus presence of HIT antibodies
• Result of antibody testing is delayed

26
Q

True or False?
• UFH, LMWH and fondaparinux are indirect
anticoagulants because they bind to
antithrombin to then go onto reduce the
activity of clotting factors in the circulation;
they act quickly because they affect clotting
factors in the circulation.

A

True

ndirect again because they require that co factor
don’t act directly on the clotting factors they require that antithrombin to bind to to undergo that conformation change and then exert effects on clotting factors and they do act quickly because they act on the clotting factors that are fleet free floating in the circulation okay.

27
Q

Initial Treatment of VTE:

Warfarin

A

Warfarin has a delayed effect – must “cross cover” using a rapid acting anticoagulant, namely a parenteral one (LMWH, fondaparinux or UFH)
– Overlap at least 5 days and until the INR is at least 2.0 for 24 hours (=2 consecutive days)
– Initiate warfarin on day 1 or 2 that parenteral is used

Those at high risk of clot (or embolism) for the 1st month of therapy, if INR falls sub-therapeutic (<2.0), “cross coverage” should be implemented with a rapid acting anticoagulant (e.g., LMWH)
– Consideration for cross coverage for sub-therapeutic INRs should be done within the 1st 3 months of therapy

minimum 5 days

28
Q

Warfarin Mechanism of Action

A

interferes with interal recylcing of vit K
prevent Vit K being reduced
carboxyl groups necessary for activation
impacts half life of clotting factors
factor II is the last step, needed to make a clot
don’t use loading doses with warfarin

29
Q

Monitoring of Warfarin Therapy

A 
Prothrombin time (PT) measures an individual patient’s
response to warfarin therapy
• International Normalized Ratio (INR) standardizes the PT to allow universal interpretation
INR = pt PT/mean normal PT
INR measures (crudely speaking) the time it takes for a blood clot to form
– INR without warfarin =1.0 (0.8-1.2)
– INR while taking warfarin either 2.0-3.0 (or 2 – 3 times as long) or 2.5 -3.5 (2.5-3.5 times as long) to form a clot
30
Q

Warfarin Side Effects and antidote

– Clinical Practice Challenges for antidotes:
• Time to treatment
• Using right antidote, right dose,
etc…
• Lack data of improved outcomes
with use of antidote
A 
• Bleeding (details later)
– Major & minor bleeding
• Teratogenic
– Hypoplastic nose, stippled epiphyses,
skeletal and ocular abnormalities
– 6-12 weeks gestation
• Much less common (rare)
– Skin necrosis
– Purple Toe Syndrome
• Antidote for Warfarin
– Vitamin K
• Intravenous or oral (urgencydependent)
– Prothrombin Complex
Concentrate (PCC)
• Factors II, VII, IX & X = blood product
• Intravenous
31
Q

Warfarin Dosing: 2 Phases

A 
1. Initiation Phase
– Establishing INR target
– Hospitalized vs Ambulatory
– Stability of Warfarin Dosing Achieved
2. Maintenance Phase
– Ongoing achievement of target INR

• 2 questions to ask yourself:
– Clot vs Bleed risk, with next INR would you prefer it above or below the target range?
– Knowing what you know now, can you justify your actions to your peers?

32
Q

Warfarin Initiation

– Important practice elements

A

• Initiation Phase typically lasts 2-4 weeks
– Dose changes in response to INRs
– Clotting factors are not at “steady state”
– “map out the patient” and appreciate the delayed impact of warfarin

  • Warfarin Initiation – Important practice elements
  • INRs should be assessed regularly (2-3 times/week)
  • Must consider the delay of warfarin’s impact and that large variation in dosing is difficult to interpret
  • Take average doses in context
33
Q

LMWH/fonda

doses for VTE Tx

A

once dai;y dosing suggested over twice dialy tx for DVT/PE

often use twice daily dosing for extensive VTEs

34
Q

warfarin considerations

A
  1. Changes to Health - assess first
    – Acute changes (fever, flu, diarrhea, etc.)
    – Chronic Medical Condition Changes:
    • Exacerbation of heart failure
    • Alterations in thyroid function
  2. Changes to Medications*
    – Prescription, non-prescription, herbals

Drug Interactions:
1. Induction / Inhibition of
Cytochrome P450
• Major 2C9 –> know that inhibitors of 2C9 should not be used
• Minor 3A4, 1A2
2. Displacement of binding plasma proteins
3. Alterations in Vitamin K Status
4. Contributing to bleeding / clotting risk

  1. Changes to Lifestyle
    – Vitamin K intake - impact INR, normal diet and if there is issue, then monitor diet
    – Alcohol Consumption - drunk, INR get high, drink in moderation (1-2 drinks a day)
    – Level of Activity - the more active, the more warfarin needed, significant changes

344 final (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions