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IPFC 3 Midterm 2 > VTE therapeutics acute treatment > Flashcards

VTE therapeutics acute treatment Flashcards

1
Q

When would you consider removal the thrombus? (2) Risk factors (5)

A
  1. PE with risk factors for poor prognosis
    - Bradycardia (<40bpm)
    - Shock (low BP with organ failure)
    - Hypotension (systolic <90)
    - Right ventricular dysfunction
    - Myocardial injury
  2. Massive DVT plus limb gangrene (amputation needed)
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2
Q

What are the 2 methods of removal of a clot

A
  1. Pharmacological (thrombolysis)
  2. Surgery (pulmonary embolectomy) for PE
    - reserved for CI to fibrinolysis (eg. active GI bleeding) or those who failed thrombolysis
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3
Q

When is an IVC filter indicated (3) (FYI)

A
  • Absolute CI to anticoagulation (active bleed, intracranial bleeding)
  • Patient survived massive PE but would not live through a 2nd one
  • Recurrent VTE despite anticoagulation
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4
Q

When do you treat a patient with acute VTE as inpatient vs outpatient?

A

Treat as outpatient only if hemodynamically stable

Hemodynamically unstable = hospital admission
- hypotension
- hypoxemia
- tachycardia

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5
Q

Do anticoagulants remove clots?

A

NO
- they only stabilize it and stop it from growing so our own body can work to dissolve it

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6
Q

Why can’t we just start with warfarin alone?

A

Warfarin only suppresses production of NEW clotting factors, does not take into account the old clotting factors that are already there

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7
Q

Risk of symptomatic worsening in an RCT of UFH + warfarin vs warfarin alone in patients with acute VTE?

A

Risk of symptomatic worsening 6.7% in combination vs 20% in warfarin alone

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8
Q

What are the factors for picking an alternative rationally in order (4)

A
  1. Efficacy
  2. Safety
  3. Cost and convenience
  4. Patient-specific factors that may modify ranking
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9
Q

Which RAPID-acting antithrombotic drug/route of admin have monitoring of effect (2)

A

UFH
- IV
- SC

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10
Q

UFH
efficacy
safety (3)

A

Efficacy
- compared to placebo in 1960, reduces risk of recurrent PE and mortality

Safety
- MAJOR BLEEDING
- thrombocytopenia
- osteoporosis

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11
Q

Explain safety trials of UFH with major bleed

A

2-5% of patients receiving IV UFH experience MAJOR BLEEDING
- a range bc of what is defined as a “major bleed”

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12
Q

When is risk of bleeding increased in UFH (4)

A
  • Recent surgery/trauma
  • conditions like peptic ulcer, malignancy, liver disease
  • NSAIDs/antiplatelets use
  • Female and over 65
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13
Q

Explain safety trials of UFH with thrombocytopenia. What are 2 possible causes of this?

A

Up to 30% of patients receiving heparin

2 causes
1. Direct effect of heparin (binding directly to platelets)
- common, not as dangerous
2. Immune reaction - HIT (heparin induced thrombocytopenia)

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14
Q

Explain safety of UFH with osteoporosis MOA. How long do you have to be on a UFH

A
  • Heparin binds to osteoblasts, which activates osteoclasts
  • associated with heparin use of 6 months
  • not entirely reversible
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15
Q

Explain pathophys of HIT (heparin induced thrombocytopenia) and treatment

A

Pathophys (immune reaction)
Occurs by 2 mechanisms:
1. removal of platelets with bound IgG by splenic macrophages
2. Platelet consumption caused by thrombus formation

Treatment
1. Stop heparin
2. Hold or reverse warfarin
3. Start a full-dose therapeutic anticoagulation with a non-heparin
- Fondaparinux (parenteral, urgent, subc)
- Argatroban

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16
Q

What are advantages of heparin over other rapid-acting anticoagulants? (2)

A
  • IV infusion can be stopped (vs SC)
  • Antidote exists - protamine sulfate
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17
Q

What is the IV weight-based dosing of UFH? How do we monitor UFH (2)?

A

Initial bolus of 80units/kg and initial infusion of 18 units/kg/ per hour

  1. adjust/monitor dosing using aPTT
    - drawn every 4-6h
  2. CBC, make sure platelets at baseline
    - q2days
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18
Q

Is SC UFH used in Canada?

A

No

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19
Q

What is the cost/convenience of UFH

A

Cost
- drug not expensive
- drug admin (monitoring, hospital stay, home care) = expensive

Convenience
- not convenient (IV, hospital stay, home care)

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20
Q

LMWH
Efficacy compared to UFH and between class
Safety (5)

A

Efficacy
- compared to UFH is similar (trials were flawed and had bias, that’s why it showed higher efficacy)

Safety (5)
- Major bleeding
- Thrombocytopenia
- Osteoporosis
- Obesity
- Renal impairment

21
Q

Dosing for dalteparin

A

200 units/kg once daily
OR
100 units/kg BID (in patients over 100kg)

22
Q

Dosing for tinzaparin

A

175 units/kg subcutaneously once daily

23
Q

Dosing for Enoxaparin

A

1mg/kg subc BID
OR
1.5mg/kg subc once daily (not encouraged for treatment of VTE because it is possibly inferior to standard dosing

24
Q

LWMH safety Major bleeding trials
Antidote?

A

Similar/lower rates compared with UFH <3%

Protamine sulfate
- only reverses about 60% of antithrombotic
- difficult to dose

25
Q

LWMH thrombocytopenia and osteoporosis trials

A

Lower rates compared to UFH

Cross reacts with HIT antibodies, but much less likely to cause HIT

26
Q

Why are LWMHs associated with a lower risk of thrombocytopenia and osteoporosis compared to UFH?

A

UFH
- chain length long enough to inhibit thrombin, can even bind to osteoblast
- enhances efficacy of anti-thrombin

LWMH, Pentasaccharide
- Chain length not enough to inhibit thrombin

27
Q

LWMH in renal impairment

A

Cleared by kidneys, can accumulate
- Avoid LWMH is CrCl < 30ml/min
- May use enoxaparin 1mg/kg DAILY instead of BID if under
- Switch to UFH instead

28
Q

Which LWMH is used for the highest total body weight

A

Dalteparin

29
Q

What is the biggest advantage of LWMH over UFH

A

Convenience
- All subcutaneously 1D or BID
- Available in pre-loaded syringes
- do not routinely require monitoring

30
Q

What do the guidelines say about therapeutic monitoring for LWMH?

A

For renal impairment, obesity, pregnancy can monitor anti factor Xa concentraitons
- better to switch to UFH though
- LWMH dosed upon body weight so not very good at targeting anti-factor Xa

31
Q

What values do we monitor for LWMH? how often?

A

CBC (including platelets)
- PT/INR
- aPTT
- SCr at baseline

CBC every 5-10 days during first 2 weeks

32
Q

Fondaparinux
Efficacy
Safety

A

Efficacy
- similar to LWMH for acute treatment

Safety
- Major bleeding (NO antidote)
- Thrombocytopenia (not a concern can be used to treat HIT)
- Renal impairment (CI in < 30)

33
Q

Fondaparinux
Dosing (3)

A

7.5 mg SC once daily
10 mg if over 100kg
2.5 mg if under 50kg

34
Q

What did the EINSTEIN-DVT + PE studies say for EFFICACY in terms of symptomatic recurrent VTE with Rivaroxaban vs Enoxaparin/warfarin

A

Rivaroxaban is not inferior to warfarin/enoxaparin for symptomatic recurrent VTE

35
Q

Could the extra monitoring in the EINSTEIN studies overestimated the benefit of rivaroxaban

A

Yes
Adherence of elderly patients to preventative therapies (eg. statins) reported to be <50% after 6 months of starting therapy
- they were routinely followed up so adherence was better
- in practice, DOAC patients are not seen as frequently

35
Q

What did the EINSTEIN-DVT + PE studies say for SAFETY in terms of major bleeding with Rivaroxaban vs Enoxaparin/warfarin

A

Rivaroxaban isn’t safer then warfarin/enoxaparin for major bleeding risk (but likely not more dangerous)
- has a little better bleeding rate in terms of %

35
Q

Rivaroxaban
Monitoring and antidose

A

None approved

35
Q

What is monitoring for warfarin for INR checks

A
  1. Daily for 1 week
  2. Twice weekly for 2 weeks
  3. Then gradually less frequently (every 4-6 weeks when stable)
36
Q

Dosing of rivaroxaban

A

15mg BID for 21 days
20 mg once daily

37
Q

Why is rivaroxaban used more commonly than apixaban

A

Apixaban is BID dosing

38
Q

Why are edoxaban and dabigatran not used for acute VTE

A

both drugs were studied with overlap with LWMH
- more expensive

39
Q

ACCP VTE guideline for VTE and no cancer of DOACs vs Warfarin

A

Rivaroxaban, apixaban, dabigatran and edoxaban have WEAK + MODERATE-quality evidence for use over Warfarin (for long term anti-coagulant therapy in VTE (no cancer)

40
Q

Duration of therapy for rapid-acting antithrombotic?
and when on warfarin?

A

5-7 days has similar to 10-14 days
- as long as it followed by an effective long-term anticoagulation

On warfarin?
- stopped after least 5 days of therapy and 2 consecutive INRs 24 hours apart that over 2.0

41
Q

Warfarin target INR and range

A

2.5
range 2-3

42
Q

When is the highest risk period for adverse effects from warfarin?

A

Within the first 30 days

43
Q

When do we use 10mg vs 5mg initiation nomogram

A

10mg
- younger patients

5mg
- older patients
- pt with high risk of bleeding (on asa)

44
Q

Elastic compression stockings ECS pressure measurement

A

Measured 30-40 mmHg ankle pressure

45
Q

Elastic compression stockings ECS in PTS prevention? treatment?

A

Prevention
- reduces risk of getting it

Treatment
- may alleviate edema and some symptoms PTS

IPFC 3 Midterm 2 (7 decks)

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