Anticoagulation Flashcards

1
Q

Thrombosis

A

Formation of a blood clot within the vascular system
Occurs normally in response to hemorrhage

May lead to:

  • Stroke
  • Pulmonary embolism
  • Myocardial infarction
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2
Q

What do you do if you suspect a DVT or PE

A

Assess clinical likelihood

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3
Q

For DVT what if low likelihood?

For PE what if not high likelihood?

A

Get D-Dimer

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4
Q

If normal D-Dimer?

A

No DVT or No PE

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5
Q

If High D-dimer or high likelihood of DVT or PE?

A

Imaging test needed

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6
Q

DVT symptoms

A
  • Mild palpation discomfort lower calf

- Massive- marked thigh swelling and tenderness during palpation of the common femoral vein

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7
Q

Pulmonary embolism symptoms

A

Dyspnea
Tachypnea
Massive- dyspnea, syncope, hypotension, cyanosis
Small embolism- pleuritic pain, cough, hemoptysis

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8
Q

What DVT imaging test should you get?

A

Venous Ultrasound

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9
Q

Venous Ultrasound Diagnostic?

A

STOP

For PE, treat for PE

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10
Q

Venous Ultrasound Nondiagnostic?

A

Get for DVT:
MRI
CT
Phelbography

Get for PE:
Transesophageal ECHO
MRI
Invasive pulmonary angiography

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11
Q

What PE imaging test should you get?

A

Chest CT

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12
Q

Chest CT Diagnostic?

A

STOP

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13
Q

Chest CT Nondiagnostic, unavailable or unsafe?

A

Get a Lung Scan

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14
Q

Lung Scan Diagnostic?

A

STOP

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15
Q

Lung Scan Nondiagnostic?

A

Get Venous ultrasound

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16
Q

What is Virchow’s triad

A
  • Hypercoagulability (Blood)
  • Stasis (Flow)
  • Endothelial Injury (Vessel)
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17
Q

Risk factors for Deep Vein Thrombosis

A

Previous thromboembolism
Age greater than 60 years or over 40 undergoing major operation
Major trauma
Prolonged immobilization (greater than 3 days)
Major orthopedic surgery
Major medical illness like CAD, HF, sepsis
Malignant disease
Hypercoagulable condition

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18
Q

Preventing DVT

A

Multiple methods alone or in combination:

Ambulation
Compression stockings
Intermittent pneumatic compression
Anticoagulants

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19
Q

Risk factors for Pulmonary Embolism

A

Same as DVT

Acute PE:
Immobilization
Surgery within the prior 3 months
Stroke
Paresis
Paralysis
Central venous instrumentation in prior 3 months
Malignancy
Chronic heart disease
Autoimmune diseases
History of venous thromboembolism
For women- obesity, heavy cigarette smoking and hypertension
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20
Q

What are the Indirect thrombin inhibitors

A

Heparin Sodium
Enoxaparin (Lovenox)
Fondaparinux (Arixtra)

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21
Q

MOA of Heparin Sodium/Unfractionated Heparin (UFH)

A

Causes a conformational change in antithrombin so that it can better pick up Factor Xa and thrombin

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22
Q

MOA of Enoxaparin (Lovenox) or Low Molecular Weight Heparins

A

Causes a conformational change in antithrombin so that it can better pick up only Factor Xa

  • weighs less than UFH
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23
Q

Fondaparinux (Arixtra)

A

Causes a conformational change in antithrombin so that it can better pick up only Factor Xa

  • Just a little more specific
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24
Q

Heparin Sodium Indications

A
  • Prophylaxis and treatment of thromboembolic disorders

- An anticoagulant for extracorporeal and dialysis procedures

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25
Enoxaparin (Lovenox) Indications
- DVT prophylaxis: Following hip or knee replacement surgery, abdominal surgery, or in medical patients with severely-restricted mobility during acute illness who are at risk for thromboembolic complications - DVT treatment: Inpatient treatment (patients with or without pulmonary embolism) and outpatient treatment (patients without pulmonary embolism)
26
Fondaparinux (Arixtra) Indications
- Prophylaxis of deep vein thrombosis in patients undergoing surgery for hip replacement, knee replacement, hip fracture (including extended prophylaxis following hip fracture surgery), or abdominal surgery - Treatment of acute pulmonary embolism - Treatment of acute DVT without PE
27
Heparin sodium dose for prophylaxis
5000 Units SC every 8 to 12 hours
28
Enoxaparin (Lovenox) dose for prophylaxis
40 mg SC once daily Knees: 30 mg SC twice a day Bariatric: BMI-based up to 60 mg SC twice a day ** need good kidney function CRCL < 30 is bad!
29
Fondaparinux (Arixtra) dose for prophylaxis
Adults 50 kg or greater: 2.5 mg SC once daily ** need good kidney function CRCL < 30 is bad!
30
Heparin sodium dose for treatment
80 units/kg IV push followed by a continuous infusion of 18 units/kg/hour 
31
Enoxaparin (Lovenox) dose for treatment
1 mg/kg SC every 12 hours 1.5 mg/kg SC once daily
32
Fondaparinux (Arixtra) dose for treatment
- Less than 50 kg: 5 mg once daily - 50-100 kg: 7.5 mg once daily - More than 100 kg: 10 mg once daily
33
Kinetics of Indirect thrombin inhibitors
No oral absorption Injection only; subcutaneous and intravenously Biological half-lives: - Heparin at 1 to 5 hours (dose dependent) - Enoxaparin at 4 to 6 hours - Fondaparinux at about 17 hours
34
Monitoring for Indirect thrombin inhibitors
Activated partial thomboplastin time (aPTT) | Anti-factor Xa levels
35
ADR of Indirect thrombin inhibitors
1. Bleeding Rates and specificity of agents Reversal agent (Protamine Sulfate for heparin) 2. Heparin-induced thrombocytopenia Drop in platelets within 5 to 10 days after exposure Thrombosis risk Antibodies against heparin/platelet factor 4 result in platelet activation, aggregation, increased platelet factor 4 and thrombin generation
36
Oral Direct Factor Xa Inhibitors?
Rivaroxaban Apixaban
37
MOA of Oral Direct Factor Xa Inhibitors?
Drug sits directly in Factor Xa
38
Differences between Oral Direct Factor Xa Inhibitors?
Kinetics: Both have a rapid onset of action Both have shorter half-lives than warfarin
39
Rivaroxaban (Xarelto) Indications
- Postoperative thromboprophylaxis in patients who have undergone hip or knee replacement surgery - Prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation - Treatment of deep vein thrombosis and pulmonary embolism - Reduce the risk of recurrent DVT and/or PE
40
Apixaban (Eliquis) Indications
To reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation
41
oral direct factor Xa inhibitors Excretion
Both agents renally excreted requiring dose adjustments in renal impairment
42
oral direct factor Xa inhibitors Drug Interactions
Both agents are substrates for CYP3A4, P-glycoprotein | Apixaban picks up minor status for CYP1A2, CYP2C19, CYP2C8, CYP2C9
43
ADR for oral direct factor Xa inhibitors
Peripheral edema Dizziness Headache Diarrhea Blood in… - Bleeding rates with rivaroxaban 21% (6% major) - Bleeding rates with apixaban 5 to 12% (2% major
44
Prescription for Xarelto™ (rivaroxaban)
20 mg | One tablet daily
45
oral direct Thrombin inhibitors
Dabigatran (Pradaxa)
46
oral direct Thrombin inhibitors MOA
Sits on thrombin (Factor IIa) and stops its effect
47
Dabigatran (Pradaxa) Indication
Prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation
48
ADR Dabigatran (Pradaxa)
- Bleeding 8 to 33% (major bleeds at 6% or less) - Gastrointestinal Dyspepsia Gastritis-like symptoms Gastrointestinal hemorrhage
49
Dabigatran (Pradaxa) dose
150 mg | One capsule twice a day
50
The injectable direct thrombin inhibitors
Bivalirudin (Angiomax™) Argatroban (Argatroban™):: - Used as an anticoagulant if HIT/HITT Infusion titrated to aPTT value (1.5 to 3 times baseline) - Critically ill patients with normal hepatic function Much lower doses may be appropriate (one-tenth) - Percutaneous coronary intervention Larger infusions doses and use of bolus dosing
51
Oral Antiplatelets
Ticlopidine **Clopidogrel Prasugrel Ticagrelor
52
Ticlopidine Indications
- Stroke prevention | - Post-coronary artery stenting
53
Clopidogrel Indications
Acute coronary syndrome (UA, NSTEMI, STEMI) Recent myocardial infarction, recent stroke or established peripheral vascular disease
54
Clopidogrel Metabolism
Prodrug- two step including 2C19***, 3A4, 2B6, 1A2
55
Oral Antiplatelets ADR
``` Adverse drug reactions - Bleeding Wide variances seen in studies All significantly lower than 5% Labeled at 4% major and 5% minor - Rash, pruritus - Gastrointestinal hemorrhage - Thrombotic thrombocytopenic purpura ```
56
Vitamin K Antagonist
Warfarin
57
Warfarin MOA
Blocks Vitamin K -->↓Thrombin formation
58
Indications for Warfarin
- Prophylaxis and treatment of thromboembolic disorders and embolic complications arising from atrial fibrillation or cardiac valve replacement - Adjunct to reduce risk of systemic embolism (e.g., recurrent myocardial infarction, stroke) after myocardial infarction
59
Dose for Warfarin
5 mg | 1 tablet daily
60
Warfarin "The time to effect"
No effect on fully carboxylated molecules 3 to 5 days to see full drug effect The “Protein C” phenomenon
61
Warfarin Plasma protein binding
Binds to albumin 99% binding --> if decrease albumin, can increase free drug and cause bleeding
62
Warfarin Monitoring the effect
International Normalized Ratio (INR) | Target for most disorders- 2 to 3
63
Warfarin Drug-drug and drug-food interactions
- Increase warfarin effect Amiodarone, ginkgo, statins, omeprazole, etc. -Decrease warfarin effect Estrogens, protease inhibitors, St Johns wort, etc.
64
Warfarin ADR
Bleeding - “Purple toe” - Reversal with phytonadione (vitamin K) Use of oral and intravenous forms: If INR 3.1, 3.2 just hold next dose.