Pharm 2 > Anticoagulants > Flashcards

Anticoagulants Flashcards

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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
When does heparin rebound occur after administration of protamine?
- patient re-anticoagulation after protamine is administered | - usually 8-9 hours
26
What medications are classified as low molecular weight heparin's?
- dalteparin - enoxaparin - tinzaparin
27
What is low molecular weight heparin's mechanism of action?
- inhibition of factor Xa by antithrombin | - some factor IIa inhibition effect
28
What monitoring is indicated with LMWH?
- anti-factor Xa levels | - aPTT and PT are relatively insensitive with LMWH therapy
29
What are indications for use of LMWH?
- atrial fibrillation - non Q-wave MI - prevention of post-op DVT/thromboembolism - recurrent DVT
30
What is an adverse side effect of LMWH?
- thrombocytopenia
31
When should you now use LMWH?
- patients with HIT | - need to decrease the dose in patients with chronic renal insufficiency
32
What are advantages of Arixtra (Fondaparinux)
- fixed dose - once daily SQ administration - not associated with HIT (but should stop if platelet count drops below 100,000)
33
What is Arixtra's mechanism of action?
- synthetic indirect inhibitor of factor Xa - Antithrombin III mediated - no effect on factor IIa - no effect on platelet function
34
What are indications for use of arixtra?
- prevention of post-op DVT/thromboembolism | - treatment of DVT or PE
35
What are the indications for use of Bevyxxa?
- prophylaxis of VTE for adults in hospital with acute medical illness - similar to lovenox
36
Is there more or less risk of a spinal or epidural hematoma with use of fondaparinux?
- same amount of risk as with use of LMWH
37
What type of medication is danaparoid sodium?
- 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
Name 3 oral Xa inhibitors.
- rivaroxaban (xarelto) - apixaban (eliquis) - edoxaban (savaysa)
39
When can warfarin be resumed after surgery?
- 12-24 hours post-op
40
When can oral anti-Xa agents be resumed after surgery?
- as soon as adequate hemostasis has been established
41
When should apixaban (Eliquis) be stopped before surgery?
- high/moderate risk procedure: 48 hours | - low risk procedure: 24 hours
42
When should xarelto be stopped before surgery?
- 24 hours
43
When should pradaxa be stopped prior to surgery?
- CrCl > 50: 1-2 days | - CrCl < 50: 3-5 days
44
What actions can be taken to reverse an oral factor Xa inhibitor?
- activated charcoal (if medication taken within 2 hours) - discontinue medication - FEIBA - mechanical compression - PCC - recombinant factor VIIa - surgical hemostasis - transfusion support
45
Are there any approved reversal agents for anti-Xa inhibitors?
- not currently, two pending approval - andexanet - ciraparantag
46
How does andexanet alpha work?
- binds competitively to factor Xa inhibitors for complete reversal
47
How does ciraparantag work?
- binds to anticoagulants through a hydrogen bond | - reverses Xa inhibitors, IIa inhibitors, fondaparinux and heparin
48
What medications are classified as direct thrombin inhibitors?
- argatroban - bivalirudin (angiomax) - hirudin - lepirudin (refludin) - dabigatran (pradaxa)
49
What polypeptide is responsible for the anticoagulant properties of the salvia in leeches?
- hirudin
50
What is the indication for use of argatroban?
- prevention and treatment of thrombosis in patients with HIT or HITTS
51
How does argatroban affect lab values?
- produces dose dependent increases in aPTT, ACT, PT and TT | - goal: aPTT 1.5-3x baseline (< 100 seconds)
52
Is there a reversal agent for argatroban?
- no
53
Hirudin is indicated for treatment of _____________.
- thrombosis associated with HIT
54
How are hirudin analogs excreted?
- excreted by kidneys and dose should be adjusted in renal impairment to
55
How do hirudin analogs work?
- bind irreversibly to active catalytic and substrate-recognition sites of both circulating and clot-bound thrombin (factor IIa).
56
Is there a reversal agent for hirudin analogs?
- no
57
How should bleeding be managed in a patient who is on dabigatran?
- 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
How does idarucizumab (Praxbind) work to reverse dabigatran?
- humanized antibody fragment | - non-competitive binding to dabigatran with 350x more affinity than thrombin
59
What were the results of the reverse AD trial?
- 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
What is warfarin's mechanism of action?
- indirect anticoagulant - alters synthesis of vitamin K dependent coagulation factors (II, VII, IX and X) by interfering with actions of vitamin K
61
Vitamin K should never be administered via what route?
- subcutaneous
62
Is warfarin safe in pregnancy?
- no | - category X
63
What drugs can interact with warfarin?
- acetaminophen - antibiotics - antiepileptics - blood thinners - NSAIDs - supplements (garlic, ginkgo, ginger)
64
What do the CHADS2-Vasc guidelines calculate?
- calculates stroke risk if patient is not on an anticoagulant
65
What does the HAS-BLED scale calculate?
- calculates bleeding risk
66
True or False Most new oral anticoagulants do not require bridge therapy as they are only held for 24-48 hours prior to surgery.
- true
67
What types of procedures are considered low/minor risk for bleeding?
- cardiac catheterization - cardiac device implantation - cataract removal - catheter ablation for afib - dental extraction - dermatology - GI endoscopy
68
What types of procedures are consider major/high risk for bleeding?
- intraabdominal surgery - intrathoracic surgery - major orthopedic surgery - peripheral arterial revascularization - urologic surgery
69
What patients are considered high risk for bridge therapy?
- 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
What patients are considered moderate risk for bridge therapy?
- 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
What patients are considered low risk for bridge therapy?
- 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
When should bridge therapy be resumed after surgery?
- LMWH: within 24-72 hours | - unfractionated heparin: within 24 hours
73
When should bridge therapy be held preoperatively?
- LMWH: 24 hours pre-procedure (recommend using 50% of regular dose for last pre-procedure dose) - unfractionated heparin: 4 hours pre-procedure
74
What does the 2017 update demonstrate regarding bridge therapy?
- 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
What types of procedures have a high risk of perioperative bleeding?
- 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
What types of procedures have a low risk of perioperative bleeding?
- abdominal hernia repair - abdominal hysterectomy - cholecystectomy - GI endoscopy - minor gynecological procedures - minor dental procedures - minor orthopedic procedures - minor plastic surgery - pacer/defibrillation insertion
77
What types of medications are not associated with an increased risk of epidural hematoma?
- aspirin | - NSAIDs
78
When can you place or remove an epidural atheter when a patient is on low dose Coumadin?
- place or remove catheter with INR < 1.5
79
True or False There is no contraindication to the use of neuraxial technique in patients who have received subcutaneous heparin.
- 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
What it's he risk of epidural hematoma after neuraxial blockade in patients treating with LMWH or fondaparinux?
- significant risk | - antiplatelet medications co-administered with LMWH may increase risk of spinal hematoma
81
What are recommendations for neuraxial anesthesia in patients being treated with direct oral anticoagulants?
- 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
When can needle placement for neuraxial anesthesia occur in patients receiving LMWH?
- 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
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