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Anticoagulants Flashcards

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1
Q

Primary hemostasis

Describes the formation of platelet plugs

A
  • Adherence
  • Activation
  • Aggregation
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2
Q

What is the MOA of UF Heparin

A

UF Heparin

It inhibits and binds to antithrombin III –> it inhibits functions of factors Xa, IIa (thrombin), IXa, XIa, XIIa

more specific : IIa

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3
Q

type of heparin that is more specific for inhibition of Xa (anti- IIa activity lower)

A

Low Molecular Weight Heparin

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4
Q

are heparins dialyzable?

A

NO

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5
Q

How is UFH eliminated?

A

UFH = Endothelial metabolism

enoxaprain and dalteparin = renal excretion

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6
Q

Advantages and disadvantages of UFH

A

* oftentimes UFH tends to have a lot of variances

UFH infusion: if you need to do an emergent procedure it takes 3 hours ideally 4 hours to come out of the system entirely.

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7
Q

Advantages and disadvantages of LMWH

A

big down side: RENAL ELIMINATION

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8
Q

BIG ADVERSE EVENTS OF HEPARINS

what is the treatment?

A

HEPARIN INDUCED THROMBOCYTOPENIA

o Development of antibodies against heparin and platelet factor 4 complex that leads to progressive thrombocytopenia and arterial and venous thrombi

o Evaluate risk with 4T score before testing for heparin antibodies and serotonin release assay

o Treatment: direct thrombin inhibitors [exam]

BLEEDING

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9
Q

How does aPTT react to LMWH

A

In general, aPTT should not change wtih LMWH

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10
Q

How do you monitor LMWH?

A

Anti factor Xa [heparin assay]

o May be used in situations where aPTT may not be reliable for UFH (e.g., lupus anticoagulant)

o Assessment of LMWH activity
• Useful if renal failure, obesity, pregnancy, or concern for

decreased bioavailability
o Assessment in cases of heparin resistance

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11
Q

The result of aPTT in patients with Lupus anticoagulant

A

aPTTs are not going to be reliable

if you use Heparin

Anti Xa should be mentioned

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12
Q

will FFP reverse heparin?

A

no.

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13
Q

what is an antidote for heparin?

A

Protamine

Mechanism of action

  • Protein derived from fish sperm [anaphylaxis for pts with fish allergy]
  • Binds to UFH or LMWH to form complex that is broken down by reticuloendothelial system

Adverse effects (generally dose and infusion rate dependent)

  • Bleeding
  • Anaphylaxis
  • Patients on maintenance NPH insulin, men with vasectomy, known fish sensitivity
  • Acute pulmonary vasoconstriction [rate dependent]
  • Hypotension
  • Bradycardia

Administration

  • Max infusion rate: 20 mg/min [exam]
  • Slow infusion rate to decrease adverse effects
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14
Q

How much does 1 mg of protamine reverse?

A

1 mg of protamine reverses 80 -120 units UFH IV

Only UFH over the past 2-3 hours should be counted

  • Protamine half-life: 7 min; heparin half-life: 60-90 min

Administration

  • No more than 50 mg in 10 min period
  • Repeat doses may be needed to fully reverse UFH
    • 0.5 mg per 100 units UFH
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15
Q

Role of Protamine and LMWH

A

LMWH –> NO reversal agent

Protamine partially effective

o Can successfully neutralize anti-IIa activity, but partially effective at reversing anti-Xa activity

  • *Dose:**
  • *Enoxaparin**
  • 1 mg per 1 mg of enoxaparin given within previous 8 hours, max dose 50 mg; may repeat with 0.5 mg for every 1 mg enoxaparin if bleeding continues
  • May repeat with 0.5 mg per 1 mg enoxaparin if >8h has elapsed since enoxaparin dose

Dalteparin

  • 1 mg per every 100 anti-Xa units given over past 3-5 half-lives,
  • max dose 50 mg
  • May repeat with 0.5 mg for every 100 anti-Xa units
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16
Q

If someone is bleeding and they have HIT what is the last factor product that you would want to give them for a reversal?

A

4F - PCC

(Kcentra)

it has heparin in it

it is contraindicated in HIT

tx: you should give 3F - PCC

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17
Q

What is the MOA of Warfarin?

What clotting factors does it inhibit?

Why do people bridge when they start warfarin?

A

Mechanism of action: WARFARIN

  • Inhibits activation of vitamin K dependent clotting factors
    • Factors II, VII, IX, X + anticoagulants protein C and protein S
  • Inhibition of anticoagulant_s increases risk for hypercoagulability at initiation of VKA without bridging_
  • Full anticoagulant affect not usually achieved until at least 4 days when factor II levels are significantly decreased
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18
Q

What is the half-life of Warfarin?

A

really long: 20- 60 hours

metabolized by CYP2C9 and affected by drugs that inhibit the metabolism of it (ccb)

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19
Q

does warfarin have renal clearance?

what are the advantages and disadvatages?

A
  • none.
  • it has tons of hepatic clearance
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20
Q

Common drug interactions with Warfarin

A
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21
Q

Drugs that potentiate warfarin effects

A
  • Amiodarane
  • Diltiazem
  • Phenytoin [can also inhibit]
  • Fluconazole
  • Voriconazole
  • argatroban [direct thrombin inhibitor] –> WILL INCREASE INR [false elevation]
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22
Q

Inhibition of warfarin effects

A
  • Seizure meds
  • phenytoin
  • phenobarb
  • rifampin [will increase the metabolism of warfarin by inducing CYP450]
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23
Q

Reversal of Warfarin

What do you do with a supratherapeutic INR without bleeding?

A
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24
Q

What do you always have to give with 4 factor PCC?

why?

A

IV vitamin K

because 4 factor PCC half-life is shorter than Warfarin

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25
How do you **reverse Warfarin** with **minor bleeding?**
**IV Vitamin K** (1-3 mg + may repeat)
26
How do you **reverse Warfarin** with **Major bleeding**?
**4 factor PCC + IV Vit K** ( 5-10 mg + may repeat) **FFP if PCC not available** (remember that this is also volume)
27
How do you reverse Warfarin in elective/nonurgent surgery How about urgent surgery?
28
MOA of Direct Thrombin Inhibitors
* Binds to free thrombin and clot-bound thrombin * decreases conversion of fibrinogen to fibrin, thrombin generation, platelet activation
29
**Drug of choice** for the management of **HIT**
## Footnote **Direct Thrombin Inhibitors**
30
What are samples of **Direct Thrombin Inhibitors**
## Footnote **Bivalirudin** **Argatroban** **Desirudin** **Dabigatran**
31
DTIs that are given IV
## Footnote **Bivalirudin** **Argatroban**
32
Route of Elimination of DTI
Bival --\> kidneys Argatroban --\> liver
33
Which drug should you give to a patient that has *HIT* that has **shock liver?**
## Footnote **Bivalurudin**
34
DIT that is oral, and longer acting (12-17 hours), very much **_dialyzable_**
**Dabigatran** **_dialyze_ like crazy if you want it off**
35
If someone came to you at the **later end of their therapy** 3-5 half-lives after cessation of therapy what should you do?
No need to do anything No role for reversal of presentation
36
A patient presented with an overdose of **Dabigatran** (early within 2 hours ) what should you do?
* Activated charcoal if administered within 2 H * **_Idarucizumab for reversal_** * **_​_**Monoclonal antibody that binds specifically to dabigatran and **acylglucuronide** metabolites at ~350 times greater than that of thrombin --\> neutralizes effects within minutes * 5 g (given as 2 separate 2.5 g doses within 15 min) IV x1 * May repeat if elevated coagulation parameters and clinically relevant bleeding present or if second urgent surgery/procedure required * Dabigatran may be started 24 h after idarcizumab, if needed
37
Why is **supportive care** in Bival, Argatroban, and Desirudin enough rather than reversing it?
due to **short half-lfe** \* if you have to absolutely [DOC] reverse _activated factor 4 PCC_ can be used **NO ROLE FOR PLASMA**
38
What are samples of **Direct Xa Inhibitors**
39
MOA of Directo Xa Inhibitors
Mechanism of action * **Bind to free factor Xa and factor Xa bound to prothrombin** complex * interrupts intrinsic and extrinsic coagulation cascade * prevents ultimate formation of thrombin
40
41
Are **Direct factor Xa inhibitors dialyzable?**
**NO.**
42
is the monitoring of NOACs required?
43
What is the **reversal agent for Factor Xa Inhibitors rivaroxaban and apixaban?**
**_Andexxa_ (first line for _rivaroxaban,_ _apixaban_)** - bolus then infusion
44
What is the **second line** reversal for **Factor Xa inhibitors**?
**Second line** o **_4-factor prothrombin complex (4F-PCC)_** 25 units/kg for life- threatening bleeding [fair enough next choice from andexxa] o **3F-PCC 25 units/kg or FEIBA** 25 units/kg in patients with history of heparin induced thrombocytopenia **_Plasma NOT routinely recommended_** o Amount of plasma needed to overcome action of NOAC would likely cause fluid overload and adverse effects
45
The **only injectable Xa inhibitor**
**Fondaparinux** **\* THE BIGGER THE PERSON THE DOSES ARE HEFTIER**
46
Fondaparinux REVERSAL
* NO DIRECT REVERSAL **DOC: activated PCC (FEIBA)**
47
How many days do you **avoid** scheduled **fibrinolytic** or **thrombolytics after neuraxial anesthesia?**
## Footnote **10 days**
48
What is the ideal time for neuraxial procedure after cessation of fibrinolytics or thrombolytics?
* ideal time for neuraxial procedures after cessation of fibrinolytics or thrombolytics is unknown, but the **suggested time is 48 hours** with documentation of normal coagulation studies
49
How can you facilitate the **assessment of neurologic function** in patients that received emergent fibrinolytics and thrombolytics that have established continuous epidural catheters??
**Minimize** the administration of **local anesthetics**
50
Guidelines for IV unfractionated heparin and neuraxial anesthesia
51
**SubQ heparin** how long do you **wait** before you start **manipulating catheters?**
## Footnote **4- 6 hours**
52
## Footnote **SubQ LMWH how long do you wait before manipulating catheters**
## Footnote **12 hours**
53
Recommendation for Factor Xa inhibitors and neuraxial anesthesia **Fondaparinux**
* **_Avoid indwelling neuraxial catheters_** and use single needle pass taking care not to have traumatic needle placement while on fondaparinux (grade 1C) * **Wait at least 6 hours** after catheter removal **to start fondaparinux** (grade 2C)
54
**Neuraxial anesthesia** recommendation with Warfarin
* **Wait at least 5 days** after the last dose of warfarin and ensure **normalized INR** before neuraxial anesthesia (grade 1B) * **Minimize** the administration of **local anesthetics** through established continuous epidural catheters in patients on concurrent warfarin to facilitate assessment of neurologic function (grade 1C) * **INR must be checked daily if warfarin is continued with an indwelling epidural catheter (grade 2C)** * Remove neuraxial catheter when INR is \< 1.5 * Indwelling neuraxial catheters may be kept with _extreme caution in patients with INRs 1.5-3 (grade 2C)_ * If INR is \> 3, stop warfarin or reduce dose while the catheter is in place (grade 1A). No recommendations can be provided regarding when to remove the catheter in this scenario (grade 2C)
55
Neuraxial anesthesia recommendation with **Direct Thrombin inhibitors** and neuraxial anesthesia
Bivalrudin and Argatroban -- \>\> NO!
56
Recommendations to hold before surgery
57
NOAC and impending surgical procedures recommendations to hold before surgery
58
What are **antiplatelet agents**
59
Antiplatelets that are **prodrugs**
* Clopidogrel * Prasugrel
60
Antiplatelet that is **reversible**
## Footnote **TICAGRELOR**
61
What is the **% platelet inhibition** of **ASPIRIN**
## Footnote **20 %**
62
What is the % platelet inhibition of **CLOPIDOGREL**
## Footnote **40 %**
63
What is the **% platelet inhibition** of ## Footnote **PRASUGREL**
## Footnote **70 %**
64
What is the **% platelet inhibition** of **TICAGRELOR**
## Footnote **95%**
65
What is a drug that is not recommended for people with a ***history of stroke/ TIA***
## Footnote **black box warning: Prasugrel** **WARNING: AGE \> 75** **WEIGHT \< 60 kg**
66
antiplatelet that may cause **bradycardia SE**
**Ticagrelor** ---\> should not be given with aspirin \>100 mg daily
67
**IV antiplatelet drug** how long before it restores platelet function after discontinuation?
**CANGRELOR** --\> practice: depending on whatever oral antiplatelet you decide there is a variety of loading mechanisms
68
MOA of GP IIb/ III a inhibitors
**GP IIb/IIIa inhibitors** ## Footnote * Inhibits **cross linkage** of **fibrinogen (final step in common** hemostatic pathway for platelet aggregation) * **_Tirofiban, eptifibatide_** * Commonly used to manage acute coronary syndrome * **Monitoring – ACT** * Reversed by clearance of drug **(short half life - ~20-40 min)**
69
Reversal of antiplatelet agents
tons of bleeding: **platelet transfusion** * If given, ideal to administer after 3-5 terminal half-lives of the antiplatelet to avoid pharmacologic inhibition of the transfused platelets
70
Reversal of antiplatelet agents **Desmopressin**
## Footnote **Increases endothelial release of factor VIII and von Willebrand factor** and may increase platelet membrane glycoprotein expressionàpromotes platelet adhesion to endothelium
71
When do you stop antiplatelets impending surgical procedures
72
Tx for High-risk patients and impending surgical procedure

Anesthesia Pharm (25 decks)

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