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module 2b > VTE - weber > Flashcards

VTE - weber Flashcards

1
Q

venous thrombi are composed of ___

A

RBCs, fibrin, few platelets

“red thrombi”

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2
Q

symptoms result when:

A

flow is obstructed, vascular tissue wall becomes inflamed, thrombus occurs and affects venous blood flow, or emboli occur and enter pulmonary circulation

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3
Q

virchow’s triad

A

hypercoaguable state - abnormalities of clotting components
endothelial injury - abnormality of surfaces in contact with blood flow
circulatory stasis - abnormalities in blood flow

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4
Q

activators of clotting system

A

von willebrand factor, tissue factor, VIIa, Xa, XIIa, thrombin (II), XIIIa, tissue plasminogen activator

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5
Q

inhibitors of clotting system

A

heparin, thrombomodulin, antithrombin, protein C, protein S, tissue factor pathway inhibitor, plasminogen activator inhibitor-1

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6
Q

postthrombotic syndrome

A
  • long term complications of DVT caused by damage to venous valves: chronic venous obstruction, caused by venous HTN, chronic pain and swelling, stasis ulcers, development of infection
  • rule out recurrent thrombosis before diagnosis
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7
Q

DVT risk factors

A

age over 40, FH, HF, immobilization over 10 days, malignancy, MI, obesity, orthopedic injury, OC/estrogen, paralysis, postoperative state, pregnancy, prior DVT, varicose veins

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8
Q

idiopathic DVT

A

we don’t know what caused it; unprovoked

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9
Q

NonPCOL treatment

A
  • baseline monitoring
  • DVT: bed rest, elevation of feet, pain management, compression stockings
  • PE: oxygen, mechanical ventilation, compression stockings
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10
Q

UFH overview

A
  • rapid anticoag
  • parenteral
  • non-specific binding
  • Non-linear kinetics: variable dose response (i.e. need for aPTT monitoring)
  • Decreased bioavailability: plasma protein binding
  • Pregnancy Category B
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11
Q

UFH uses

A
  • prophylaxis and treatment of thromboembolic disorders

- anticoagulant for extracorporeal and dialysis procedures

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12
Q

UFH MOA

A

-Interacts with ATIII which catalyzes the formation of thrombin:antithrombin
complexes
-Binds to heparin co-factor and catalyzes inactivation of factor IIa -Binds to platelets

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13
Q

UFH lab monitoring

A
  • Close monitoring required
  • activated Partial Thromboplastin Test (aPTT) is utilized
  • Commercial test vary therefore follow institution specific range
  • 1.5 – 2.5 times normal control = therapeutic range
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14
Q

UFH dosing

A
  • Dosing protocols
  • IV or SubQ (NOT IM)
  • Old standard: 5000 unit IV bolus; 1000 – 1200 units per hour
  • Subcutaneous: 5000 units subQ every 8-12 hours (proph)(8 hours if crcl above 50; 12 if below); 17500 units every 12 hours (treatment)
  • Weight based (actual body weight)(recommended): 80 units/kg IV bolus; 18 units/kg/hr infusion
  • Given for at least 5 days with warfarin
  • concern for incompatibility
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15
Q

UFH dosing adjustments

A
  • check aPTT at baseline
  • Check 6 hours after dose or with each dosage change (for first 24 hours)
  • Check daily after first day – unless out of range
  • Adjust dose based on results
  • aPTT less than 1.2x normal: 80 U/kg bolus, then increase rate by 4 U/kg/h
  • aPTT 1.2-1.5x normal: 40 U/kg bolus, then increase rate by 2 U/kg/h
  • aPTT 2.3-3x normal: Decrease infusion rate by 2 U/kg/h
  • aPTT over 3x normal: Hold infusion 1 h, then decrease infusion rate by 3 U/kg/h
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16
Q

UFH PK

A
  • Subcutaneous dosing: Bioavailability 30-70%, Onset 1-2 hours; peak 3 hours
  • IV dosing: Half life: 30-90 minutes (dose dependent), Continuous infusion preferred
    3. Elimination
    a. Inactivation via heparinases and desulfatases (rapid, saturable)
    b. Renal (slower, non-saturable)
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17
Q

UFH AE

A
  • Bleeding: Major bleeding 0-2% (without other concomitant risks), Thrombocytopenia
  • Osteoporosis: Doses > 20,000 units/day, Duration > 6 months (i.e. during pregnancy)
  • Hypersensitivity
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18
Q

thrombocytopenia

A
  1. HAT: heparin associated thrombocytopenia
  2. HIT: heparin induced thrombocytopenia
  3. Check platelet counts every other day until day 14
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19
Q

why get CBC if pt is bleeding?

A

we want to know Hgb and Hct

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20
Q

minor bleeding

A
  • Superficial bruising
  • Nosebleeds that resolve
  • Gum bleeding that resolves
  • Blood on tissue when blowing nose
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21
Q

major bleeding

A
  • IF PATIENT IS UNCOMFORTABLE W AMOUNT OF BLOOD
  • Unresolved epistaxis
  • Hematuria
  • BRBPR
  • Spontaneous hematomas
  • Hemoptysis
  • Hematemesis
  • Hematuria
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22
Q

treatment related bleeding risk factors

A

dose, duration, route

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23
Q

patient related bleeding risk factors

A
  • Age > 65
  • h/o GI bleed or PUD
  • Comorbid diseases
  • Concurrent medications
  • EtOH use
  • Renal failure
  • Malignancy
  • Cerebrovascular disease
  • Surgery/major trauma
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24
Q

bleeding management

A

1-Monitor: HGB, HCT, & blood pressure

2. If occurs: Discontinue heparin, may require blood transfusion, Protamine sulfate administration

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25
Q

protamine sulfate

A
  • MOA: cationic protein binds to anionic heparin
  • Neutralizes heparin in 5 min; persists for 2 hours
  • Half-life: 7 min
  • Repeat aPTT 30 minutes after administration of protamine
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26
Q

protamine sulfate dosing

A

immediate: 1-1.5 (mg per 100 units UFH)
30-120 minutes: 0.5-0.75
over 2 hours: 0.25-0.375

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27
Q

protamine sulfate adverse reactions

A

-Hypotension, bradycardia: Slow IV infusion (over 1-3 minutes), Max 50 mg over 10 minutes
-Anaphylaxis: Received protamine-containing insulin, h/o vasectomy, fish
sensitivity

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28
Q

HAT

A
  • Also known as HIT-Type I
  • Non-immune mediated
  • Mild decrease in platelets (>100,000/mm3)
  • Occurs around 48-72 hours after administration of heparin
  • Transient
  • Do not need to d/c heparin
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29
Q

HIT

A
  • Immune mediated
  • Thrombotic complications
  • Occurs between: 7-14 days
  • Can occur up to 9 days after stopping therapy
  • Platelets drop >50% from baseline or
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30
Q

HIT clinical presentation

A
  • Thrombocytopenia: Platelets decrease by >50% OR Decrease to less than 100,000/mm3
  • Venous thromboembolic complications
  • Heparin-induced skin lesions

D/C all heparin products

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31
Q

when d/c heparin in suspected HIT, start ___

A

argatroban, danaparoid, or fondaparniux

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32
Q

duration of therapy

A

if had previous thrombi - continue as directed by guidelines

if develop thromosis during HIT continue for at least 3 months

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33
Q

LMWH

A
  • Fragments of UFH
  • Heterogeneous mixture of sulfated glycosaminoglycans
  • Approximately 1/3rd the molecular weight of UFH
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34
Q

LMWH labeled uses

A

-ACS (UA, NSTEMI, STEMI)
-DVT treatment
-Prophylaxis following TKA, THA, abdominal surgery, acute medical
patients

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35
Q

advantages of LMWH

A

good bioavailability, predictable dose response, resistance not encountered, fixed or weight-based dosing, no monitoring required, QD or BID, improved SQ abs, reduced incidence of HIT and bleeding

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36
Q

LMWH MOA

A
  • Activates ATIII
  • Reduced ability to bind thrombin
  • Retains ability of inactivate factor Xa
  • 3-4X more affinity for X over II
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37
Q

LMWH PK

A
  • Subcutaneous dosing: 90% bioavailability, Peak effect 3-5 hours
  • Eliminated renally: Plasma half-life 2-4 x longer than UFH
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38
Q

LMWH examples

A

enoxaparin, dalteparin, tinzaparin

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39
Q

enoxaparin dosing

A

Prophylaxis: 30 mg SQ BID, 40 mg SQ QD
treatment: 1mg/kg SQ BID, 1.5 mg/kg SQ QD
renal dysfunction: 30 mg SQ QD (prophylaxis), 1 mg/kg SQ QD (treatment)

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40
Q

dalteparin dosing

A

prophylaxis: 2500-5000 IU SQ QD
treatment: 200 IU/kg SQ QD (max 18000 IU)
renal dysfunction: monitor Xa levels; goal: 0.5-1.5 4-6 hours post)

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41
Q

tinzaparin dosing

A

treatment: 175 anti-Xa IU/kg SQ QD

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42
Q

LWMH special population

A
  • Obesity: Enoxaparin up to 144 kg, Dalteparin up to 190 kg, Tinzaparin up to 165 kg
  • Pregnancy category B
  • Consider anti-factor Xa levels
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43
Q

LMWH monitoring

A

Adverse Effects/Toxicity: CBC with platelet, Serum creatinine, Fecal occult blood

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44
Q

anti Xa monitoring

A
  • Consider for children, severe kidney failure, obesity, long courses, pregnancy
  • Treatment: Twice daily dosing: 0.6-1.0 units/mL obtained 4 hours post dose, Once daily dosing: 0.1-0.3 units/mL obtained as trough (can consider peak of 1-2 units/mL obtained 4 hours post dose)
  • Routine monitoring not recommended
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45
Q

LMWH black box warning

A

-All LMWH products have the same warning
-Use with neural anesthesia or spinal puncture can lead to increased risk of spinal
hematoma leading to paralysis

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46
Q

LMWH AE

A
  • Bleeding: Major/minor
  • Thrombocytopenia: Less than UFH, Monitor platelets
  • Delayed hypersensitivity skin reactions
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47
Q

LMWH bleeding management

A
  • D/C LMWH
  • Best neutralization method not as clear
  • Protamine sulfate administration: Within 8 hours of last LMWH dose( 1 mg per 100 anti-factor Xa units; 1 mg per 1 mg enoxaparin), over 8 hours (0.5 mg per 100 anti-factor Xa units; 0.5 mg per 1 mg enoxaparin)
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48
Q

factor Xa inhibitors

A
  • Indirect agents: binds to antithrombin (like heparin): Fondaparinux (Arixtra®)
  • Drect agents: binds to factor Xa: Rivaroxaban (Xarelto), Apixaban (Eliquis®), Edoxaban, Betrixaban (not approved for use in US)
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49
Q

fondaparinux labeled uses

A
  • usually acute, can be maintenance in specific patients
  • Prophylaxis following THA, TKA, hip replacement, or abdominal surgery
  • Treatment of DVT or PE
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50
Q

fondaparinux dosing

A
  • prophylaxis: 2.5 mg subQ once daily (hip, knee, or abdominal surgery)
  • Treatment:
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51
Q

fondaparinux PK

A
  • Peak plasma activity: 2-3 hours
  • Eliminated in urine: Half-life 17-21 hours, Anticoagulation effects lasts 2-4 days post discontinuation
  • No binding to other proteins, including platelets or PF4: No risk of HIT
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52
Q

fondaparinux special considerations

A

-Do not use if have renal dysfunction (CrCl

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53
Q

fondaparinux BBW

A

Use with neural anesthesia or spinal puncture can lead to increased risk of spinal
hematoma leading to paralysis

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54
Q

fondaparinux monitoring

A
  • No routine monitoring for therapeutic efficacy: Can monitor anti-Xa levels (similar to LMWH)
  • Serum creatinine
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55
Q

fondaparinux AE

A

bleeding

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56
Q

rivaroxaban uses

A 
NOAC
acute and maintenance
-DVT prophylaxis
-DVT treatment
-NV Afib
-PE treatment
-reduction in the risk (secondary prevention) of recurrent DVT and/or PE
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57
Q

rivaroxaban dosing

A
  • DVT prophylaxis: 10 mg daily - 6-10 hours post surgery (confirmed hemostasis); THA: continue for 35 days; TKA: continue for 12 days
  • DVT/PE treatment: 15 mg BID x 3 weeks, then 20 mg daily with food
  • Non-valvular atrial fibrillation: 20 mg daily (CrCl > 50 mL/min)
  • CrCl 15-50 mL/min: 15 mg once daily
  • Secondary prevention: 20 mg daily - Duration: 6-12 months, following initial treatment of 6-12 months
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58
Q

rivaroxaban antidote

A

No antidote for reversal (not dialyzable)

  • PCC has been shown to be beneficial in trials
  • Andexanet alfa: directed factor Xa antidote (Phase III trials)
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59
Q

rivaroxaban PK

A

-Metabolized by CYA 3A4/5: Caution: strong CYP3A4 inhibitors, PGP inhibitors, other products
affecting hemostasis
-Time to peak: 2-4 hours
-Half life: adults 5-9 hours; elderly 11-13 hours

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60
Q

rivaroxaban DI

A

-P-gp and CYP3A4 inducers: Carbamazepine, phenytoin, rifampin, St. John’s wort

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61
Q

rivaroxaban AE

A
  • bleeding

- Avoid: CrCl

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62
Q

warfarin to rivaroxaban

A

stop warfarin and start rivaroxaban when INR less than 3

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63
Q

rivaroxaban to warfarin

A

Start warfarin and stop rivaroxaban 3 days
later
OR IF continuous, uninterruped
anticoagulation is necessary:
stop rivaroxaban, begin both parenteral anticoagulation (LMWH or UFH) and warfarin at the time the next dose of rivaroxaban would have
been given and stop the parenteral anticoagulant when
INR reaches an acceptable range

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64
Q

LMWH/ fondaparinux to rivaroxaban

A

Stop parenteral anticoagulant and administer rivaroxaban 0-2 hours before the next dose of parenteral drug would have been given

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65
Q

IV heparin to rivaroxaban

A

Administer first dose of rivaroxaban at the same time as discontinuation of IV heparin infusion

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66
Q

rivaroxaban to parenteral anticoagulant

A

Stop rivaroxaban and administer first dose of parenteral anticoagulant at the time the next dose of rivaroxaban would have been given

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67
Q

rivaroxaban to oral anticoagulant other than warfarin

A

Stop rivaroxaban and begin the other anticoagulant at the time that the next scheduled dose of rivaroxaban would have been given

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68
Q

rivaroxaban black box warning

A
  • spinal/epidural hematomas

- premature d/c increases risk of thrombotic event

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69
Q

apixaban uses

A 
NOAC 
acute and maintenance 
-DVT prophylaxis
-DVT treatment
-NV Afib
-PE treatment
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70
Q

apixaban dosing

A

-DVT prophylaxis: 2.5 mg PO BID: Start 12-24 hours postoperatively (hemostasis confirmed); THA: continue for 35 days; TKA: continue for 12 days
-DVT/PE treatment: 10 mg PO BID x 7 days, then 5 mg BID: Can continue 2.5 mg PO BID ≥ 6 months (following initial 6-12 months) for reduction in risk recurrence
-Non-valvular atrial fibrillation: 5 mg PO BID: 2.5 mg PO BID (2 of the following): age ≥ 80 years, weight under 60
kg, SCr ≥ 1.5 mg/dL; Dialysis: 5 mg PO BID; 2.5 mg PO BID if age over 80 years OR
weight under 60 kg

71
Q

apixaban antidote

A

No antidote for reversal currently approved (not dialyzable)

  • PCC or rFVIIa can be considered
  • Andexanet alfa: directed factor Xa antidote (Phase III trials)
72
Q

apixaban PK

A
  • Metabolized by CYA 3A4/5: Caution: strong CYP3A4 inhibitors, PGP inhibitors, other products affecting hemostasis
  • Time to peak: 3-4 hours
  • Half life: 5 mg dose = 15 hours; 2.5 mg dose = 8 hours
73
Q

apixaban cautions

A

-avoid use with Strong 3A4 inhibitors and inducers, dabigatran etexilate,
rivaroxaban, and St. Johns Wort
-Adverse reactions: bleeding
-Caution: Patients with CrCl

74
Q

warfarin to apixaban

A

stop warfarin and start apixaban when INR less than 2

75
Q

apixaban to warfarin

A

start warfarin and stop apixaban 3 days later OR IF continuous, uninterrupted anticoagulation is
necessary: Stop apixaban, Begin both a parenteral anticoagulant (LMWH/fondaparinux or UFH) and warfarin at the same time that the next dose of apixaban would have been given, Stop the parenteral anticoagulant when INR is over 2.

76
Q

LMWH/fondaparinux to apixaban

A

stop LMWH/fondaparinux and start apixaban at the same time that the next dose of LMWH/fondaparinux would have been given

77
Q

IV heparin to apixaban

A

Stop IV heparin and start apixaban simultaneously

78
Q

apixaban to parenteral anticoagulant

A

stop apixaban and administer first dose of parenteral anticoagulant at the time that the next dose of apixaban would have been given

79
Q

apixaban to oral anticoagulant other than warfarin

A

stop apixaban and begin the other anticoagulant at the time that the next scheduled dose of apixaban would have been given

80
Q

apixaban BBW

A

spinal/epidural hematomas

premature discontinuation increases the risk of thrombotic event

81
Q

edoxaban uses

A

NOAC
acute or maintenance
-DVT/PE treatment
-NVAF

82
Q

edoxaban dosing

A
  • Non-valvular atrial fibrillation: CrCl 50 - 95 mL/min: 60 mg once daily; CrCl 15 - 50 mL/min: 30 mg once daily
  • DVT/PE Treatment: Following 5-10 days of initial parenteral anticoagulant therapy; CrCl greater than 50 mL/min: 60 mg once daily; 30 mg once daily: with 1 or more of the following: CrCl 15 to 50 mL/min, Body weight less than 60 kg, OR Use of P-gp inhibitors
83
Q

edoxaban antidote

A

No antidote for reversal (not dialyzable): PCC or rFVIIa can be considered, Andexanet alfa: directed factor Xa antidote (Phase III trials)

84
Q

edoxaban PK

A

-Metabolism: Minimal via hydrolysis, conjugation, and oxidation by CYP3A4;
PGP substrate, Predominant metabolite (M-4) is active (

85
Q

edoxaban caustions

A
  • Caution: other products affecting hemostasis
  • Adverse reactions: bleeding
  • Avoid: Child-Pugh Class B or C
  • Pregnancy category C
86
Q

warfarin to edoxaban

A

Stop warfarin and start edoxaban with INR less than 2

87
Q

Edoxaban to warfarin

A

Start warfarin and stop edoxaban 3 days later Manufacturer recommends: for patients taking 60mg, reduce edoxaban to 30mg and start warfarin concomitantly. Stop edoxaban when INR > 2, for patients taking 30mg, reduce edoxaban to 15mg and start warfarin concomitantly. Stop edoxaban when INR > 2
OR if continuous , uninterrupted anticoagulation is necessary: stop edoxaban, begin both a parenteral anticoagulant
(LMWH/fondaparinux or UFH) and warfarin at the same time
that the next dose of edoxaban would have been givenc) stop the parenteral anticoagulant when the INR is > 2

88
Q

LMWH/Fondaparinux to

edoxaban

A

Stop LMWH/Fondaparinux and start edoxaban at the same time that the next dose of LMWH/fondaparinux would have been given

89
Q

IV heparin to edoxaban

A

Stop IV heparin and start edoxaban simultaneously
(manufacturer recommends starting edoxaban 4 hrs after
stopping IV heparin)

90
Q

Edoxaban to parenteral

anticoagulant

A

Stop edoxaban and start the parenteral anticoagulant at the same time that the next dose of edoxaban would have been given

91
Q

Edoxaban to oral anticoagulant other than warfarin

A

Stop edoxaban and start the other anticoagulant at the same time that the next scheduled dose of edoxaban would have been given

92
Q

edoxaban BBW

A
  • Reduced efficacy in nonvalvular atrial fibrillation patients with CrCl >95 mL/minute
  • Spinal/epiduarl hematomas
  • Prematue discontinuation increases the risk of thrombotic event
93
Q

direct thrombin inhibitors

A

direct agents: prevent thrombin generation by binding to circulating and clot-bound fibrin
IV: lepirudin, bivalirudin, argatroban
NOAC: dabigatran
-Mechanism of action: Interact directly with thrombin molecule, Do not require antithrombin
-No antidote for reversal: lepirudin, bivalirudin, argatroban
-Useful in HIT treatment

94
Q

lepirudin

A

dose: 0.15 mg/kg/h (± 0.4
mg/kg bolus)
Use: HIT -Goal aPTT 1.5-2.5 normal
notes: Reduce dose CrCl

95
Q

bivalirudin

A

Dose: 0.7 mg/kg, then 1.75
mg/kg/h
Use: HIT, UFH alternative
during PCI

96
Q

argatroban

A 
dose: 
Normal: 2 mcg/kg/min
Hepatic: 0.5 mcg/kg/min
Use: HIT 
Notes: Elevates INR, overlap with warfarin until INR ≥ 4; Caution hepatic dysfunction
97
Q

dabigratran uses

A

NOAC

  • DV/PE treatment
  • NVAF
98
Q

dabigratran dosing

A

-DVT/PE Treatment: 150 mg PO BID (after 5-10 days of parenteral anticoagulation); Patients with CrCl

99
Q

dabigratran cautions

A
  • Recommend alternate agent: age over 75 years
  • Must be kept in manufacturer bottle (expires 4 months after opening)
  • Adverse reactions: dyspepsia, bleeding
100
Q

dabigratran PK

A
  • Time to peak: 1 hour (2 hours with food)
  • Half-life: 12-17 hours; 15-28 hours mild – severe renal impairment
  • metabolism: Dabigatran etexilate: plasma & hepatic esterases to active form; Dabigatran: hepatic glucuronidation
101
Q

Warfarin to dabigatran

A

Stop warfarin and start dabigatran when INR less than 2

102
Q

Dabigatran to warfarin

A

-Clcr over 50 mL/min: start warfarin and stop dabigatran 3 days later
-Clcr 31-50 mL/min: start warfarin and stop dabigatran 2 days later
-Clcr 15-30 mL/min: start warfarin and stop dabigatran 1 day later
(dabigatran may alter INR results; therefore, using INR to guide when to stop dabigatran is not reliable)

103
Q

LMWH/ fondaparinux to dabigatran

A

Stop parenteral anticoagulant and administer dabigatran 0-2 hours before next parenteral dose would have been given

104
Q

IV heparin to dabigatran

A

Administer first dose of dabigatran at time of discontinuation of IV heparin infusion

105
Q

Dabigatran to parenteral

anticoagulant

A

Clcr over 30 mL/min: Start parenteral anticoagulant 12 hours after the last dose of dabigatran
Clcr under 30 mL/min: Start parenteral anticoagulant 24 hours after the last dose of dabigatran

106
Q

dabigatran to oral anticoagulant other than warfarin

A

stop dabigatran and begin the other anticoagulant at the time that the next dose of dabigatran would have been given

107
Q

dabigratran CI

A

mechanical heart valve

active bleeding

108
Q

dabigratran BBW

A

thrombotic events

spinal/epidural hematomas

109
Q

idarucizumab (praxbind) use

A

-Reversal of dabigatran anticoagulant effects

110
Q

idarucizumab dose

A

5 g intravenous (administered as 2 separate 2.5 g doses no more than 15 minutes apart)

111
Q

idarucizumab ADR

A

delirium (7%), HA (5%), hypokalemia (7%), constipation (7%), pneumonia (6%), fever (6%)

112
Q

idarucizumab monitoring

A

Baseline aPTT (at presentation), repeat at 2 hours postexposure (if exposure time is known) or post-presentation (if exposure time is unknown) and every 12 hours thereafter until aPTT returns to normal

113
Q

idarucizumab onset

A

Effects observed within minutes and hemostasis is restored at a median of 11.4 hours
duration: 24 hours
half-life elimination: 47 minutes (initial); 10.3 hours (terminal)
-excreted in the urine

114
Q

3 goals of anticoags:

A
  • stabilize clot
  • prevent propagation of clot
  • minimize risk of embolism

NOT to get rid of clot - body has mechanisms to do so

115
Q

thrombolytics

A
  • “clot busting drug”
  • NOT recommended for routine use for VTE
  • If used, suspend anticoagulant use during thrombolytic: Following use: restart anticoagulant when aPTT is less than 80 seconds
116
Q

thrombolytics absolute CI

A
  • Any prior ICH
  • Structural cerebral vascular lesion
  • Malignant IC neoplasm
  • Ischemic stroke within 3 months
  • Suspected aortic dissection
  • Active bleeding or bleeding diathesis (excluding menses)
  • Significant closed-head or facial trauma within 3 months
117
Q

thrombolytics cautions/relative CIs

A
  • Severe HTN (SBP>180 mmHg)
  • Ischemic stroke > 3 months
  • Major surgery
118
Q

thrombolytic examples

A
  • tpa, alteplase (activase) - only one we use to dissolve clot
  • reteplase
  • tenecteplase
  • urokinase
119
Q

alteplase dosing and considerations

A 
Bolus: 10 mg
Infusion: 90 mg over 2
hours
-Total dose = 100 mg over 2 hours
-Not weight based
-Most commonly used for PE
120
Q

reteplase considerations

A

only used for ACS

121
Q

tenecteplase considerations

A

only used for ACS

122
Q

urokinase dosing and considerations

A

Bolus: 4400 units/kg x 10 min
Infusion: 4400 units/kg/hour over 12 hours

123
Q

warfarin

A
  • Most widely prescribed anticoagulant
  • Warfarin is available as brand and generic products
  • Available in 1, 2, 2.5, 3, 4, 5, 6, 7.5, and 10mg tablets
124
Q

warfarin labeled uses

A
  • Prophylaxis and treatment of thromboembolic disorders (eg, venous, pulmonary) and embolic complications arising from atrial fibrillation or cardiac valve replacement
  • Adjunct to reduce risk of systemic embolism (eg, recurrent MI, stroke) after myocardial infarction
125
Q

challenges of warfarin

A
  • Narrow therapeutic window
  • Considerable inter-subject variability
  • Drug and diet interactions
  • Labs difficult to standardize
  • Good PK/PD understanding by both patient/provider
126
Q

warfarin MOA

A
  • Does not effect circulating factors or previously formed thrombi
  • Inhibits enzymes responsible for cyclic conversion of vitamin K
  • Inhibit synthesis of vitamin K dependent clotting factors: Factors II, VII, IX, and X; Protein C and S
127
Q

half life of proteins

A
  • Prothrombin (factor II): 60-100 hours
  • Factor VII: 4-6 hours
  • Factor IX: 20-30 hours
  • Factor X: 24-40 hours

important when bridging to warfarin - need to get rid of existing clotting factors since warfarin won’t directly inhibit them

128
Q

warfarin PK

A
  • Anticoagulant effect within 24 hours: Peak effect 72-96 hours, Duration of action from single dose: 2-5 days
  • Mixture of S and R isomers: S isomer 5 times more potent
  • Rapid absorption from GI tract: Maximal concentrations in ≈ 90 minutes
  • Hepatically metabolized: CYP P450 (S: 2C9, 2C19, 2C18; R: 1A2, and 3A4); DRUG INTERACTIONS!!!!; Genetic Variances
  • Pregnancy Category X
129
Q

warfarin dosing algorithms

A 
CYP2C9*1/*1:
GG: 5-7, GA: 5-7, AA: 3-4
CYP2C9*1/*2:
GG: 5-7, GA: 3-4, AA: 3-4
CYP2C9*1/*3:
GG: 3-4, GA: 3-4, AA: 0.5-2
CYP2C9*2/*2:
GG: 3-4, GA: 3-4, AA: 0.5-2
CYP2C9*2/*3:
GG: 3-4, GA: 0.5-2, AA: 0.5-2
CYP2C9*3/*3:
GG: 0.5-2, GA: 0.5-2, AA: 0.5-2
130
Q

who should be tested?

A

patient is warfarin naive, genetic tests are available before the 6th dose, patient is at a high risk of bleeding if INR is elevated

131
Q

warfarin monitoring

A
  • PT: reduction of factors II, VII, and X: Monitoring NOT standardized
  • INR= (patient PT/mean normal PT)ISI - ISI: international sensitivity index
  • Narrow therapeutic window
132
Q

INR: higher the number the ___ it takes to clot

133
Q

normal INR

134
Q

goal INR

A

usually 2-3

135
Q

indications for goal INR 2-3

A 
prophylaxis of VTE
treatment of VTE or PE
prevention of systemic embolism: tissue heart valves, AMI (2.5-3.5), valvular heart disease, afib
antiphospholipid antibody syndrome
mechanical heart valve (aortic)

mechanical heart valve (MITRAL): 2.5-3.5

136
Q

warfarin dosing

A
  • Variable over time
  • Variable between patients
  • Initial dose: 5 mg by mouth once daily; Healthy outpatients: 10 mg daily x 2 days
  • Overlap with UFH/LMWH/Xa for at least 5 days AANNNDDDD until INR is therapeutic
  • Adjust weekly dose to achieve therapeutic INR
137
Q

warfarin dosing exceptions

138
Q

dose alterations for INR 2-3

A

INR less than 2: increase 5-15%
INR 3.1-3.5: decrease 5-15%
INR 3.5-4: hold 0-1 dose and decrease by 10-15%
INR over 4: hold 0-2 doses and decrease by 10-15%

for goal 2.5-3.5: all the same but +0.5

139
Q

initiation of warfarin therapy - frequency of INR monitoring

A
  • Flexible initiation method: Daily through day 4, then within 3-5 days
  • Average daily dosing method: Within 3-5 days, then within 1 week
  • After hospital discharge : If stable, within 3-5 days; If unstable, within 1-3 days
  • First month of therapy: Weekly
140
Q

maintenance therapy of warfarin - frequency of INR monitoring

A
  • Dose held today:Within 1-2 days
  • Dose change today:Within 1-2 weeks
  • Dosage change less than 2 wks ago:Within 2-4 weeks
  • Routine follow-up stable pt: Every 4-6 weeks
  • Routine follow-up unstable pt: Every 1-2 weeks
  • Consistently stable (i.e. no change in 6 months): Every 12 weeks
141
Q

point of care warfarin monitoring

A

1-Self-testing: send result to healthcare provider

  • Self-managed: self-adjust warfarin
  • Appropriately selected and trained patients; Anticoagulated over 3 months, Good cognitive skills, dexterity, and communication
  • Mechanical heart valves, atrial fibrillation, VTE
142
Q

warfarin patient interview

A

The 5 D’s

  • Drugs (any changes in medications)
  • Diseases (any changes in overall medical condition and/or treatment)
  • Doses (any missed doses)
  • Diet (any changes in diet, specifically green leafy vegetables)
  • Drink (any EtOH consumption)

Bruising/bleeding

143
Q

warfarin dose adjustments

A
  • Signs/symptoms of bleeding
  • Thromboembolic complications
  • Prescription medication changes
  • Diet
  • Activity
  • EtOH use
  • Adverse effects
  • OTC drug use
  • Drug interaction screening
144
Q

duration of therapy (minimums)

A
  • Reversible risk factor: 3 months
  • Idiopathic DVT: at least 3 months, then re-evaluate; Consider extended therapy up to 1 year
  • DVT + cancer: LMWH for 3-6 months, then warfarin or LMWH indefinitely or cancer resolves
  • Multiple events: lifelong therapy; consider at least 3 months if at high bleeding risk
145
Q

warfarin drug interaction risks

A
  • Hepatic metabolism
  • Plasma protein binding
  • Increased risk of bleeding
146
Q

increase INR drug interactions with warfarin

A
  • Erythromycin
  • Metronidazole*
  • Amiodarone*
  • Alcohol (acute ingestion)
  • Cimetidine
  • Anabolic steroids
  • Fluconazole*
  • Isoniazid
  • Liver disease
  • Ciprofloxacin*
  • Bactrim*
  • Propafenone

*=adjust dose

147
Q

aspirin and warfarin

A

increase risk of bleeding without increasing INR

148
Q

decrease INR drug interactions with warfarin

A
  • Rifampin*
  • Cholestyramine
  • Carbamazepine
  • Alcohol (chronic ingestion)
  • Vit K foods

*=adjust dose

149
Q

food-drug warfarin interaction

A
  • Role of vitamin K; Reverses warfarin activity, Contained in several foods, Need patient education
  • Consistency is key
  • Monitoring
150
Q

alcohol and warfarin

A
  • Acute EtOH: Increase anticoagulant effect of warfarin by inhibiting its metabolism
  • Chronic EtOH w/o liver damage: Enhances warfarin metabolism by inducing hepatic enzymes decreases the effect of warfarin
  • Chronic EtOH w/ liver damage: Due to lack of hepatic enzymes, increased anticoagulant effect (dose reduction often needed)
151
Q

warfarin AE

A

bleeding

pregnancy category X

152
Q

bleeding management with warfarin

A
  • Dependent on INR and presence/absence of bleeding: Vitamin K (Oral: 5 mg tablets, Parenteral: do NOT exceed 1 mg/min (anaphylaxis)); Fresh Frozen Plasma (FFP) (10-15 mL/kg); Prothrombin Complex Concentrate (PCC) (30 IU/kg (check INR before, 30-60 minutes after))
  • INR 4.5-10.0 NO evidence of bleeding: avoid vitamin K
  • INR > 10.0 NO evidence of bleeding: PO vitamin K
  • Major bleeding while on warfarin: PCC preferred over FFP: May add vitamin K 5-10 mg as well
153
Q

warfarin reversal

A
  • rapid (10-15 min): Prothrombin complex concentrate (immediate replacement of vitamin K-dependent coagulation factors) plus intravenous vitamin K (to switch on endogenous synthesis of vitamin K-dependent coagulation factors within a few hours)
  • fast (partial): Fresh frozen plasma (immediate replacement of vitamin K dependent coagulation factors – but the correction of coagulopathy is partial)
  • prompt (4-6 hours): IV Vit K
  • slow (24 hours): PO Vit K
  • very slow (3-5 days): omit warfarin
154
Q

VTE prophylaxis

A
  • Without prophylaxis: VTE incidence 5-15% in medical patients (EVERY PATIENT MUST BE EVALUATED FOR ANTICOAG NEED)
  • Without prophylaxis: VTA incidence 40-80% in surgical patients
  • Up to 40% qualified medical patients don’t receive appropriate prophylaxis
155
Q

VTE propylaxis options

A
  • Unfractionated heparin (UFH)
  • Low-molecular weight heparin (LMWH)
  • Factor Xa Inhibitors
  • Vitamin K antagonists
156
Q

low risk VTE

157
Q

moderate risk VTE

A

VTE risk 10-40%

  • Most non-orthopedic surgery patients
  • Acutely ill medical patients (limited mobility)
  • General surgery patients: UFH, LMWH, and Factor Xa inhibitor (fondaparinux) all recommended, VTE risk continues post hospital discharge (40% of events > 21 days after surgery), Continue prophylaxis up to 28 days after hospital discharge
  • Acutely ill medical patients: UFH, LMWH, and fondaparinux all appropriate, Increased VTE risk due to early discharge/immobility at home, No specific recommendations for post-discharge VTE prophylaxis duration
158
Q

high risk VTE

A

VTE risk 40-80%

  • Most orthopedic surgery
  • Major trauma
  • Spinal cord injury
  • Orthopedic surgery (TKA or THA): LMWH, fondaparinux, rivaroxaban, apixaban, UFH, or vitamin K antagonist – FDA approved, Dabigatran possibility – non-FDA approved, Continue ≥ 10-14 days postop (consider up to 35 days)
159
Q

high bleeding risk ___ prophylaxis preferred

A

Mechanical prophylaxis preferred

  • Intermittent pneumatic compression devices
  • Venous foot pumps
  • Graduated compression stockings
160
Q

VTE treatment (initial DVT or PE treatment)

A
  • SubQ LMWH, IV or subQ UFH, fondaparinux: Initiate warfarin Day 1-2 of treatment, Overlap warfarin + injectable anticoagulant (At least 5 days AND INR > 2.0 for 24 hours, Warfarin 5-10 mg usual starting dose)
  • Rivaroxaban or apixaban: DOES NOT need warfarin overlap, continue medication for treatment duration
  • Edoxaban: DOES NOT need warfain overlap, continue parenteral anticoagulant for 5-10 days
  • Dabigatran: DOES NOT need warfain overlap, continue parenteral anticoagulant for 5-10 days
161
Q

VTE treatment (thrombolytic use)

A
  • Preferred VTE treatments on previous slides
  • Majority of VTE patients don’t require thrombolytics

IF NEEDED:

  • DVT: extensive proximal DVT (i.e. risk of losing the limb), low bleeding risk: Catheter directed or systemic
  • PE: associated with hypotension (SBP
162
Q

Afib

A
  • has not had a clot, but use whats considered “treatment level” anticoag
  • Mechanical heart valve: warfarin recommended (INR 2.0-3.0 or 2.5-3.5)
  • Non-valvular afib: CHA2DS2-VASc recommended to assess risk
  • Non-valvular afib with prior stroke, TIA, or CHA2DS2-VASc at least: oral anticoagulants: Warfarin, rivaroxaban, apixaban, edoxaban, dabigatran
  • CHA2DS2-VASc = 1: no antithrombotic therapy OR oral anticoagulant OR ASA considered
  • CHA2DS2-VASc = 0: omit antithrombotic therapy
163
Q

CHADS2VASc is only used ___

A

to determine the need the need for anticoag in AFib patients

164
Q

CHA2DS2VASc acronym and score

A 
CHF - 1
HTN - 1
Age over 75 -2
DM - 1
Stroke/TIA/TE - 2
Vascular disease - 1
Age 65-74 - 1
sex (female) - 1
165
Q

AFib rivoroxaban dosing

A
  • 20 mg daily with the evening meal

- CrCl 15-50 mL/min: 15 mg daily

166
Q

AFib apixaban dosing

A
  • . 5 mg BID

- at least 80 yrs, wt under 60 kg, sCr at least 1.5 mg/dL (any 2): 2.5 mg BID

167
Q

AFib edoxaban dosing

A
  • CrCl 50-95 mL/min: 60 mg daily

- CrCl 15-50 mL/min: 30 mg daily

168
Q

AFib dabigratran dosing

A
  • 150 mg BID
  • CrCl 30-50 w/ dronedarone or ketoconazole: 75 mg BID
  • CrCl 15-30: 75 mg BID
169
Q

AFib warfarin dosing

A

5 mg daily (bridging with parenteral anticoagulant not recommended)

170
Q

invasive prodecures

A
  • “Bridging therapy” may be needed if on warfarin
  • Typically not needed for dental, dermatologic, or cataract procedures
  • If bridging is needed: Stop warfarin 5 days before surgery, Give LMWH or UFH until the procedure (Stop LMWH 24 hours before procedure; Stop IV UFH 4-6 hours before procedure), Resume warfarin 12-24 hours after surgery (assuming adequate hemostasis)
171
Q

D/C dabigatran before procedure

A 
CrCl 30-49
-low risk: over 48 hours
-high risk: over 96 hours
CrCl 50-79
-low risk: over 36 hours
-high risk: over 72 hours
CrCl above 80
-low risk: over 24 hours
-high risk: over 48 hours
172
Q

D/C Xa inhibitors before procedure

A 
CrCl 15-29
-low risk: over 36 hours
-high risk: over 48 hours
CrCl above 30
-low risk: 24 hours
-high risk: over 48 hours
173
Q

VKORC

A

1639A: inc sens
1639G: inc resistance

module 2b (9 decks)

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