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Pharm 2 > Anticoagulants > Flashcards

Anticoagulants Flashcards

1
Q

What is the source of heparin?

A
  • bovine lung

- porcine intestinal mucosa

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2
Q

What is heparin’s mechanism of action?

A
  • increases the rate of the thrombin-antithrombin III reaction at least 1000-fold by being a catalyst in template that binds antithrombin III and protease bind
  • heparin induces conformational change in antithrombin III that makes the reactive site more accessible to protease
  • after thrombin is bound to antithrombin III heparin molecule is released
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3
Q

What are indications for use of heparin?

A
  • acute MI
  • anticoagulation during arterial/cardiac surgery
  • diagnosis and treatment of DIC
  • non Q-wave MI
  • percutaneous coronary intervention
  • pregnancy complications
  • prophylaxis of postoperative DVT and PE
  • prophylaxis and treatment of VTE
  • prophylaxis and treatment of of peripheral arterial embolism
  • unstable angina
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4
Q

What is heparin’s onset?

A
  • IV: immediate

- SQ: 1-2 hours

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5
Q

What is the half life of heparin?

A
  • 100 units/kg = 1 hour
  • 400 units/kg = 2.5 hours
  • 800 units/kg = 5 hours
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6
Q

How is heparin metabolized?

A
  • cleared by the reticuloendothelial system
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7
Q

True or False

Heparin crosses the placenta.

A
  • false

- heparin does not cross the placenta

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8
Q

What types of factors does heparin work on?

A
  • only acts on unbound factors
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9
Q

What causes heparin resistance?

A
  • accelerated clearance of drug with massive PE
  • acquired antithrombin III deficiency in patients with cirrhosis, nephrotic syndrome or DIC
  • increased concentration of factor VIII
  • ## inherited antithrombin III deficiency
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10
Q

How can you treat heparin resistance caused by an acquired antithrombin III deficiency?

A
  • administer 2 units of FFP to provide antithrombin III

- antithrombin III concentrate

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11
Q

What are signs and symptoms of heparin toxicity?

A
  • abnormal LFTs
  • bleeding
  • osteoporosis
  • spontaneous vertebral fractures
  • thrombocytopenia
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12
Q

What is the occurrence of major bleeds caused by heparin?

A
  • 1-33% of patients
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13
Q

What lab values are associated with heparin induced thrombocytopenia (HITT)?

A
  • platelets < 100,000
  • 7-14 days after initiate of full or low dose heparin therapy (including heparin flush solution).
  • can occur earlier if patient has been previously exposed to platelets
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14
Q

What causes HITT?

A
  • heparin dependent antiplatelet IgG antibiotics or a direct nonimmunogenic effect on platelets
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15
Q

How is HITT treated?

A
  • stop the heparin
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16
Q

What is the reversal agent of heparin?

A
  • protamine sulfate
  • acts as a heparin antagonist by creating complex with strongly acidic and anionic heparin to form a stable salt
  • removed by the reticuloendothelial system
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17
Q

What are indications for use of protamine sulfate?

A
  • neutralize heparin after CPB procedures or other procedures where higher molecular weight heparin was used
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18
Q

What type of heparin is not as susceptible to protamine antagonism?

A
  • low molecular weight heparin’s (anti-factor Xa agents).

- emergency reversal needed = protamine will neutralize about 65% of anti-xa activity of LMWHs

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19
Q

What is the dose of protamine for reversal of heparin?

A
  • 1-1.5mg of protamine for every 100 unites of heparin.
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20
Q

What are the adverse effects of protamine sulfate?

A
  • acute histamine-related hypotension
  • bradycardia
  • dyspnea
  • pulmonary hypertension
  • transient flushing
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21
Q

What should be monitored when administering protamine sulfate by rapid IV injection?

A
  • airway pressures (wheezing)
  • blood pressure
  • PA pressures
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22
Q

What types factors can increase hypersensitivity to protamine sulfate?

A
  • hypersensitive to fish
  • previous protamine reversal of heparin
  • previous vasectomy
  • protamine containing insulin (NPH)
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23
Q

What is the pretreatment for a patient with a potential hypersensitivity to protamine sulfate?

A
  • antihistamine

- corticosteroid

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24
Q

What can occur with an overdose of protamine sulfate?

A
  • bleeding (theoretically) because it has anticoagulant and anti-platelet effects when given alone or in excess of heparin
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25
Q

When does heparin rebound occur after administration of protamine?

A
  • patient re-anticoagulation after protamine is administered

- usually 8-9 hours

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26
Q

What medications are classified as low molecular weight heparin’s?

A
  • dalteparin
  • enoxaparin
  • tinzaparin
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27
Q

What is low molecular weight heparin’s mechanism of action?

A
  • inhibition of factor Xa by antithrombin

- some factor IIa inhibition effect

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28
Q

What monitoring is indicated with LMWH?

A
  • anti-factor Xa levels

- aPTT and PT are relatively insensitive with LMWH therapy

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29
Q

What are indications for use of LMWH?

A
  • atrial fibrillation
  • non Q-wave MI
  • prevention of post-op DVT/thromboembolism
  • recurrent DVT
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30
Q

What is an adverse side effect of LMWH?

A
  • thrombocytopenia
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31
Q

When should you now use LMWH?

A
  • patients with HIT

- need to decrease the dose in patients with chronic renal insufficiency

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32
Q

What are advantages of Arixtra (Fondaparinux)

A
  • fixed dose
  • once daily SQ administration
  • not associated with HIT (but should stop if platelet count drops below 100,000)
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33
Q

What is Arixtra’s mechanism of action?

A
  • synthetic indirect inhibitor of factor Xa
  • Antithrombin III mediated
  • no effect on factor IIa
  • no effect on platelet function
34
Q

What are indications for use of arixtra?

A
  • prevention of post-op DVT/thromboembolism

- treatment of DVT or PE

35
Q

What are the indications for use of Bevyxxa?

A
  • prophylaxis of VTE for adults in hospital with acute medical illness
  • similar to lovenox
36
Q

Is there more or less risk of a spinal or epidural hematoma with use of fondaparinux?

A
  • same amount of risk as with use of LMWH
37
Q

What type of medication is danaparoid sodium?

A
  • heparinoid (not a LMWH or true heparin_
  • almost exclusively anti-Xa activity
  • relatively loss cross reactivity for patients with a history of HIT (but can still cause HIT).
38
Q

Name 3 oral Xa inhibitors.

A
  • rivaroxaban (xarelto)
  • apixaban (eliquis)
  • edoxaban (savaysa)
39
Q

When can warfarin be resumed after surgery?

A
  • 12-24 hours post-op
40
Q

When can oral anti-Xa agents be resumed after surgery?

A
  • as soon as adequate hemostasis has been established
41
Q

When should apixaban (Eliquis) be stopped before surgery?

A
  • high/moderate risk procedure: 48 hours

- low risk procedure: 24 hours

42
Q

When should xarelto be stopped before surgery?

A
  • 24 hours
43
Q

When should pradaxa be stopped prior to surgery?

A
  • CrCl > 50: 1-2 days

- CrCl < 50: 3-5 days

44
Q

What actions can be taken to reverse an oral factor Xa inhibitor?

A
  • activated charcoal (if medication taken within 2 hours)
  • discontinue medication
  • FEIBA
  • mechanical compression
  • PCC
  • recombinant factor VIIa
  • surgical hemostasis
  • transfusion support
45
Q

Are there any approved reversal agents for anti-Xa inhibitors?

A
  • not currently, two pending approval
  • andexanet
  • ciraparantag
46
Q

How does andexanet alpha work?

A
  • binds competitively to factor Xa inhibitors for complete reversal
47
Q

How does ciraparantag work?

A
  • binds to anticoagulants through a hydrogen bond

- reverses Xa inhibitors, IIa inhibitors, fondaparinux and heparin

48
Q

What medications are classified as direct thrombin inhibitors?

A
  • argatroban
  • bivalirudin (angiomax)
  • hirudin
  • lepirudin (refludin)
  • dabigatran (pradaxa)
49
Q

What polypeptide is responsible for the anticoagulant properties of the salvia in leeches?

A
  • hirudin
50
Q

What is the indication for use of argatroban?

A
  • prevention and treatment of thrombosis in patients with HIT or HITTS
51
Q

How does argatroban affect lab values?

A
  • produces dose dependent increases in aPTT, ACT, PT and TT

- goal: aPTT 1.5-3x baseline (< 100 seconds)

52
Q

Is there a reversal agent for argatroban?

A
  • no
53
Q

Hirudin is indicated for treatment of _____________.

A
  • thrombosis associated with HIT
54
Q

How are hirudin analogs excreted?

A
  • excreted by kidneys and dose should be adjusted in renal impairment to
55
Q

How do hirudin analogs work?

A
  • bind irreversibly to active catalytic and substrate-recognition sites of both circulating and clot-bound thrombin (factor IIa).
56
Q

Is there a reversal agent for hirudin analogs?

A
  • no
57
Q

How should bleeding be managed in a patient who is on dabigatran?

A
  • activated charcoal (if medication taken within 2 hours)
  • discontinue drug
  • HD will remove 62-68% of circulating medication
  • mechanical compression
  • PCC
  • recombinant factor VIIa
  • specific antidotes: idarucizumab, ciraparantag)
  • surgical hemostasis
  • transfusion support
58
Q

How does idarucizumab (Praxbind) work to reverse dabigatran?

A
  • humanized antibody fragment

- non-competitive binding to dabigatran with 350x more affinity than thrombin

59
Q

What were the results of the reverse AD trial?

A
  • elderly multi morbidity patients with life-threatening emergencies required reversal of anticoagulation because of uncontrolled bleeding or need for emergency surgery or invasive procedure
  • median time from reversal to procedure was 1.6 hours for invasive procedures
  • median time to investigator reported hemostasis was 2.5 hours
60
Q

What is warfarin’s mechanism of action?

A
  • indirect anticoagulant
  • alters synthesis of vitamin K dependent coagulation factors (II, VII, IX and X) by interfering with actions of vitamin K
61
Q

Vitamin K should never be administered via what route?

A
  • subcutaneous
62
Q

Is warfarin safe in pregnancy?

A
  • no

- category X

63
Q

What drugs can interact with warfarin?

A
  • acetaminophen
  • antibiotics
  • antiepileptics
  • blood thinners
  • NSAIDs
  • supplements (garlic, ginkgo, ginger)
64
Q

What do the CHADS2-Vasc guidelines calculate?

A
  • calculates stroke risk if patient is not on an anticoagulant
65
Q

What does the HAS-BLED scale calculate?

A
  • calculates bleeding risk
66
Q

True or False

Most new oral anticoagulants do not require bridge therapy as they are only held for 24-48 hours prior to surgery.

A
  • true
67
Q

What types of procedures are considered low/minor risk for bleeding?

A
  • cardiac catheterization
  • cardiac device implantation
  • cataract removal
  • catheter ablation for afib
  • dental extraction
  • dermatology
  • GI endoscopy
68
Q

What types of procedures are consider major/high risk for bleeding?

A
  • intraabdominal surgery
  • intrathoracic surgery
  • major orthopedic surgery
  • peripheral arterial revascularization
  • urologic surgery
69
Q

What patients are considered high risk for bridge therapy?

A
  • mechanical heart valves (aortic and mitral valve replacements, stroke or TIA within 6 months)
  • atrial fibrillation (stroke or TIA within 3 months, rheumatic valvular heart disease)
  • VTE (VTE within 3 months, severe thrombophilia)
70
Q

What patients are considered moderate risk for bridge therapy?

A
  • mechanical heart valve (bileaflet aortic valve prosthesis with either afib, prior stroke/TIA, HTN, diabetes, CHF or > 75)
  • atrial fibrillation
  • VTE (within 2-12 months)
71
Q

What patients are considered low risk for bridge therapy?

A
  • atrial fibrillation (with no previous stroke/TIA)
  • VTE (single VTE over 12 months ago with no other risk factors)
  • mechanical heart valve (bileaflet aortic valve replacement without afib and no other risk factors for stroke)
72
Q

When should bridge therapy be resumed after surgery?

A
  • LMWH: within 24-72 hours

- unfractionated heparin: within 24 hours

73
Q

When should bridge therapy be held preoperatively?

A
  • LMWH: 24 hours pre-procedure (recommend using 50% of regular dose for last pre-procedure dose)
  • unfractionated heparin: 4 hours pre-procedure
74
Q

What does the 2017 update demonstrate regarding bridge therapy?

A
  • questionable benefit to bridge therapy
  • no reduction in thromboembolic events and increase risk of bleeding
  • 40-60% of anticoagulant interruptions may be unnecessary
  • continue medications if bleeding risk is very low
75
Q

What types of procedures have a high risk of perioperative bleeding?

A
  • major cardiac, neurological, orthopedic, urologic or vascular surgeries
  • major cancer treatments
  • kidney biopsy
  • endoscopically guided fine needle aspiration
  • major surgery with duration greater than 45 minutes
76
Q

What types of procedures have a low risk of perioperative bleeding?

A
  • abdominal hernia repair
  • abdominal hysterectomy
  • cholecystectomy
  • GI endoscopy
  • minor gynecological procedures
  • minor dental procedures
  • minor orthopedic procedures
  • minor plastic surgery
  • pacer/defibrillation insertion
77
Q

What types of medications are not associated with an increased risk of epidural hematoma?

A
  • aspirin

- NSAIDs

78
Q

When can you place or remove an epidural atheter when a patient is on low dose Coumadin?

A
  • place or remove catheter with INR < 1.5
79
Q

True or False

There is no contraindication to the use of neuraxial technique in patients who have received subcutaneous heparin.

A
  • true
  • no contraindication
  • delay injection until after the block
  • patients on heparin more than 4 days should have a platelet count checked to rule out HIT
80
Q

What it’s he risk of epidural hematoma after neuraxial blockade in patients treating with LMWH or fondaparinux?

A
  • significant risk

- antiplatelet medications co-administered with LMWH may increase risk of spinal hematoma

81
Q

What are recommendations for neuraxial anesthesia in patients being treated with direct oral anticoagulants?

A
  • all medications currently have black box warning for use with neuraxial anesthesia
  • medications should be discontinued prior to procedure
  • can be restarted 24 hours post procedure for low bleed risk and 48-72 hours for high bleed risk
82
Q

When can needle placement for neuraxial anesthesia occur in patients receiving LMWH?

A
  • should occur at least 10-12 hours after last LMWH
  • high doses of LMWH require a delay of at least 24 hours
  • epidural should be placed 6-8 hours prior to any dose of postoperative LMWH (once a day dosing)
  • twice daily dosing of LMWH should be delayed until 24 hours post-operative
  • removal should be done 2-4 hours before a dose of LMWH
  • removal should occur 10-12 hours after any dose

Pharm 2 (19 decks)

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