Anticoagulant Drug Use

Report
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Knowledge of the commonly used anticoagulant drugs is
important in reducing the likelihood of patient harm
associated with their administration.
Common drugs used for therapeutic anticoagulation are
warfarin (Coumadin), unfractionated heparin (commonly
referred to as heparin) and low molecular weight heparin
(LMWH, ex: Lovenox).
Newer oral anticoagulants include dabigatran (Pradaxa),
rivaroxaban (Xarelto), and apixaban (Eliquis).
 Objectives

Learn mechanism of action of warfarin
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Explain warfarin dosing and monitoring parameters
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Identify adverse drug events that can be caused by warfarin
administration
Understand key patient counseling points
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Interferes with liver activation of vitamin K-dependent
coagulation factors (II, VII, IX, X)
Warfarin has no effect on coagulation factors already present
in the circulation and therefore it takes time to see the clinical
effect of warfarin.
Onset of action (or clinical activity) varies from 36-72 hours

The Initial Inpatient Warfarin Dose Order (WC) is to be used.
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Most patients can be initiated with 5 mg given by mouth daily

Dosage adjustments are based on the target International
Normalized Ratio (INR) as determined by patient’s indication

The INR result is to be obtained within the 48 hours prior to
initiation. Then every 24, 48, or 72 hours INRs are to be
drawn until goal is met.

It is NOT acceptable to give warfarin without INR result.
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For most indications, the goal INR is 2-3.

Bleeding is the major adverse effect of warfarin. Hemorrhage
may occur at any site.
Common drugs/classes known
to increase warfarin effect:
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Acetaminophen
Allpurinol
Amiodarone
Aspirin
Cephalosporins
Citalopram
Diltiazem
Fish oil
Fluconazole
Fluoroquinolones
Heparins
Isoniazid
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Macrolides
Metronidazole
NSAIDS
Omeprazole
Propafenone
Quinidine
Sertraline
Thyroxine
Trimethoprim-Sulfa

Provide patient with a printed “Warfarin Medication Guide”
and verbal information about the medication
The following points should be reviewed with patient/family:
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Purpose of warfarin therapy
Identification of generic and brand name products
Warfarin administration and dosing (missed doses, duration of therapy)
and importance of compliance
Purpose and need for INR testing
Drug interactions (Avoid aspirin, ibuprofen, alcohol, herbals)
Consistent intake of foods containing Vitamin K (green leafy vegetables)
Monitor for signs of bleeding (nose, mouth, GI, GU) and call MD if
serious
Communicate warfarin use to other healthcare professionals
Consult with a pharmacist or other health care professional when taking
any new medications (OTC, prescription or herbal)
Document patient education and their comprehension
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Consider the patient’s future anticoagulation needs when
planning the reversal of warfarin. Large doses of vitamin K do
not reverse anticoagulation faster and may cause a period of
warfarin resistance
See the Warfarin Reversal Protocol, which can be viewed on
the BJC.net site, under Pharmacy and then Anticoagulation
Resources. It may also be viewed in the order entry section of
Compass under “warfarin reversal” or “phytonadione for
elevated INR due to warfarin.

o
o
o
o
The clinical effects of warfarin are seen within
8 hours
24 hours
36-72 hours
5 days

The clinical effects of warfarin are seen within
36-72 hours. Warfarin has no effect on
coagulation factors already present in the
circulation and therefore it takes time to see
warfarin’s clinical effect.

o
o
o
o
The major side effect of warfarin is
bleeding
skin necrosis
diarrhea
itching

These are all potential side effects of
warfarin, but the major concern with this
medication is bleeding. Warfarin may cause
severe bleeding that can be life-threatening
and even result in death. A new medication
called Kcentra (4-Factor Prothrombin
Complex Concentrate) may be used to treat
severe life-threatening bleeds in conjunction
with phytonadione (Vitamin K).

o
o
o
o
o
o
Which of the following points should be
included when counseling a patient on
warfarin?
Drug interactions
Importance of INR monitoring
Compliance
Dietary precautions
Monitoring for signs of bleeding
All of the above
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It is important to counsel patients about drug
interactions, follow-up lab monitoring,
compliance, dietary precautions, and how to
monitor for signs of bleeding. All these
points need to be addressed because they
can impact therapeutic outcomes.
Patient education is essential for effective oral
anticoagulation.

o
Irma N Reynolds is an 86 y/o female who presents to the ED
with complaints of frequent nose bleeds that are hard to stop
since she was started on warfarin for atrial fibrillation. Which
of the following is the most appropriate?
Tell Irma this is a known side effect of warfarin and to come
back if it gets worse
o
Give patient fresh frozen plasma and 10mg Vitamin K IVPB
o
Check her INR
o
Tell her to hold her next 2 doses of warfarin and then
continue taking as prescribed
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
In this situation, it would be appropriate to check
the patient’s INR prior to making any changes in
therapy. The INR value will give you an indication
as to her risk of bleeding, and then adjustments
in therapy.
The 2012 CHEST Guidelines recommend to hold
the warfarin dose & “monitor” patient if INR is
less than or equal to 10, and there is no evidence
of bleeding, and there is no planned
surgery/procedure within 24 hours. Vitamin K
offers no advantage.

Objectives
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Learn mechanism of action of heparin
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Explain heparin dosing and monitoring parameters
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Identify adverse drug events that can be caused by heparin
administration
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Heparin enhances the action of antithrombin III, thereby
blocking thrombosis through inactivation of Factor Xa and
inhibition of prothrombin’s conversion to thrombin. This also
prevents fibrin formation from fibrinogen during active
thrombosis.
Its onset of action is immediate when administered
intravenously and approximately 20-30 minutes when given
subcutaneously
This drug is not for IM use
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An activated partial thromboplastin time (aPTT) should be
ordered before initiation, 6 hours after initial heparin
bolus/infusion, and 6 hours after any change in rate of the
infusion
When 2 consecutive aPTTs are therapeutic (1.5-2.5 times the
control aPTT, the aPTT should be monitored at least daily
BJWCH therapeutic aPTT range: 60-100 seconds
CBC with platelets (or hemogram) should be monitored before
initiation and every 72 hours throughout therapy. PT/INR
should be monitored before initiation.
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Hypersensitivity to heparin or any component of the
formulation
Severe thrombocytopenia including heparin-induced
thrombocytopenia
Uncontrolled active bleeding except when due to
disseminated intravascular coagulation
Suspected intracranial hemorrhage
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It should be given as a weight-based bolus dose followed by
weight-based infusion rate which is adjusted according to the
patient’s aPTT.
The indication for the use and patient’s risk of bleeding
determines the initial starting heparin infusion rate.
For the treatment of deep vein thrombosis (DVT)/pulmonary
embolism, heparin should be administered (with the initiation
of warfarin) for at least 5 days and/or until there are 2
consecutive therapeutic INRs.
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Fever, headache, chills, erythrema/injection site ulcer after
subcutaneous injection
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Hyperkalemia, hematoma
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Heparin-induced thrombocytopenia
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Increase hepatic aminotransferase levels
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Osteoporosis with long-term, high dose administration
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Discontinuation of all forms of heparin including flushes for
line maintenance
Alternatives to heparin in these patients include Argatroban ,
lepirudin (Refludan), and bivalirudin (Angiomax) if needed.
Warfarin therapy if needed is contraindicated until platelet
count has recovered to at least > 100,000/mm3

Which lab test should be ordered 6 hours after initial heparin
bolus and start of heparin infusion and its result is used to
make dosage adjustments?
o
PT
o
INR
o
Anti-Xa
o
aPTT
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The aPTT is used to monitor heparin anticoagulation therapy.
The PT and INR test is used to evaluate the effectiveness of
warfarin therapy, while the anti-Xa test monitors patients on
low molecular weight heparin (ex: Lovenox)

Heparin can be given as a weight-based bolus dose followed
by a weight-based infusion rate, which is adjusted according
to the patient’s aPTT.
o
True
o
False
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True
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Heparin is associated with which of the following side effects?
o
Purple toes syndrome
o
Hyponatremia
o
Thrombocytopenia
o
Dizziness

Heparin-induced thrombocytopenia is a serious side effect of
heparin therapy. This is characterized by a decrease in
platelets by more than 50% from baseline or an absolute
platelet count of < 100,000/mm3 following exposure to
heparin or low molecular weight heparin.
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Patients who develop heparin-induced thrombocytopenia
(HIT) can be treated with all of the following except:
o
Argatroban
o
Enoxaparin
o
Bivalirudin
o
Lepirudin
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Patients with heparin-induced thrombocytopenia should not
be treated with enoxaparin. All forms of heparin products
should be discontinued. Alternatives to heparin therapy
include argatroban, bivalirudin, and lepirudin.
Only argatroban is available at BJWCH.
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Objectives
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Learn mechanism of action of LMWH
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Explain LMWH dosing and monitoring parameters
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Identify adverse drug events that can be caused by LMWH
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Understand key counseling points
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LMWH has a small effect on the activated partial
thromboplastin time (aPTT) and is a strong inhibitor of factor
Xa
Enoxaparin (Lovenox) has an onset of action of around 3-5
hours and is renally excreted
These drugs are not for IM use
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Anti-factor Xa level monitoring can be considered in patients
with poor renal function and the morbidly obese
CBC with platelets (of hemogram) and serum creatinine
should be monitored before initiation and throughout therapy
every 3 days.
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Hypersensitivity to the drug, heparin, or pork products
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Active major bleeding
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Thrombocytopenia
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The black box warning with these agents is as follows:
 Patients with recent or anticipated neuraxial anesthesia (epidural or spinal
anesthesia) are at risk of spinal or epidural hematoma and subsequent
paralysis
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For the treatment of DVT/PE, LMWH should be administered
(with the initiation of warfarin) for at least 5 days and/or until
there are 2 consecutive therapeutic INRs
The dose of enoxaparin for treatment of DVT/PE, unstable
angina and non-ST segment elevation myocardial infarction
(UA/NSTEMI) is 1mg/kg subcutaneously every 12 hours (in
patients with a CrCl < 30 ml/min the enoxaparin dose is
1mg/kg subcutaneously every 24 hours). Treatment of
DVT/PE may also be given as 1.5mg/kg every 24 hours.
In patients with morbid obesity (BMI > 40) and normal renal
function, a starting dose of 0.75mg/kg subcutaneously every
12 hours is recommended along with Anti-Xa monitoring.
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Hemorrhage (includes cases of intracranial, retroperitoneal,
or intraocular hemorrhage)
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Thrombocytopenia including HIT
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Hypochromic anemia
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Elevated transaminase levels
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Injection site hematoma and local reaction (irritation, pain,
ecchymosis, erythema)
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Lovenox kits/booklets are available from pharmacy to provide
to patients.
Review and follow all of the steps to ensure proper
administration and safe disposal of Lovenox pre-filled
syringes. Administration should be alternated between the
left and right anterolateral and left and right posterolateral
abdominal wall. To minimize bruising, do not rub the
injection site after completion of the injection.
Monitor for signs of bleeding
Periodic serum creatinine, CBC including platelet counts, and
stool occult blood tests are recommended to monitor drug
therapy
Which of the following statements are TRUE about enoxaparin?
o
Is a strong inhibitor of Factor VIIa
o
Is also known as unfractionated heparin
o
Can be administered intramuscularly (IM)
o
Should be renally dose adjusted
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Enoxaparin dose should be adjusted in patients with
decreased renal function since it is eliminated in the urine.
This low molecular weight heparin is a strong inhibitor of
factor Xa and cannot be administered IM.
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Low molecular weight heparins (LMWH) are not associated
with thrombocytopenia.
o
True
o
False
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Heparin-induced thrombocytopenia is a serious adverse event
that can occur in any patient exposed to heparin. This drug
reaction is associated with unfractionated and low molecular
weight heparin.
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Which of the following patients should not receive a
LMWH?
o
Patient with an allergy to heparin and pork products
o
Patient with active major bleeding
o
Patient with epidural anesthesia
o
All of the above
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All of the above are contraindications to the use of low
molecular weight heparins. In addition to patients with
hypersensitivity, this medication should be avoided in
patients with active bleeds because it can exacerbate their
condition. Giving the medication in patients with epidural
anesthesia increases the risk of spinal or epidural hematoma.
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Objectives
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Learn mechanism of action of dabigatran (Pradaxa)
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Explain dosing and monitoring parameters
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Identify adverse drug events that can be caused by DTI
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Understand key counseling points
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Dabigatran (Pradaxa) is the only orally available DTI in the US
Dabigatran is only indicated to reduce the risk of stroke and
systemic embolism in patients with nonvalvular atrial
fibrillation.
Dabigatran is a prodrug and it is a reversible and selective
direct thrombin inhibitor. It inhibits thrombin and thrombininduced platelet aggregation.
It has a fast onset of action with peak levels reached within 14 hours. Half-life is 8-17 hours depending on renal function.
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A baseline serum creatinine is required prior to starting
therapy. Serum creatinine should be monitored periodically
throughout therapy
There are no requirements for coagulation monitoring.
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Dabigatran should not be taken by patients with an active
pathological bleed
Dabigatran should not be taken by patients with a serious
hypersensitivity to carrageenan, FD&C blue #2, FD&C yellow
#6, hypromellose, potassium chloride, titanium dioxide, or
black edible ink.
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The recommended dose is 150mg po BID in patients with a
CrCl > 30 ml/min and 75mg po BID if CrCl is 15-30 ml/min
Dabigatran capsules should be swallowed whole, without
chewing, breaking, or opening
Dabigatran may be taken with or without food
A missed dose should be skipped if it cannot be taken at
least 6 hours before the next schedule dose
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Dabigatran can cause serious and potentially fatal bleeding.
Bleeding risk increases with age and decrease renal function
Thrombosis may occur with abrupt discontinuation of
dabigatran
Gastritis-like symptoms have occurred in 35% of patients
taking dabigatran
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Provide patient with a copy of the “Pradaxa Medication Guide”
and verbal information about the medication
The following points should be reviewed with patient/family:
 Take as prescribed
 Remind patient not to discontinue Pradaxa without talking to MD
(increased risk of thrombosis)
 Purpose of therapy & compliance
 Dabigatran administration and dosing (missed doses)
 Don’t chew or break the capsule before swallowing
 Call MD if they experience dyspepsia or gastritis
 Monitor for signs of bleeding or thrombosis
 Communicate dabigatran use to other healthcare professionals
 Objectives
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Learn mechanism of action of rivaroxaban (Xarelto) and
apixaban (Eliquis)
Explain dosing and monitoring parameters
Identify adverse drug events that can be caused by
Factor Xa Inhibitors
Understand key counseling points
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Rivaroxaban (Xarelto) and apixaban (Eliquis) are currently the only
orally available Factor Xa Inhibitors available in the US
Rivaroxaban and apixaban are both indicated to reduce the risk of
stroke and systemic embolism in patients with nonvalvular atrial
fibrillation.
Rivaroxaban has additional indications including deep vein
thrombosis (DVT)/pulmonary embolism (PE) prophylaxis after hip or
knee replacement surgery, treatment of PE or DVT, & the reduction
in risk of recurrence of PE or DVT.
Factor Xa Inhibitors directly antagonize factor Xa and are a
reversible inhibitor of the factor Xa active site. They block the final
process of the coagulation cascade.
They have a fast onset of action. Half-life of rivaroxaban is 5-13
hours and apixaban is 8-15 hours depending on renal function.
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A baseline serum creatinine is required prior to starting
therapy. Serum creatinine should be monitored periodically
throughout therapy
There are no requirements for coagulation monitoring
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Factor Xa Inhibitors should not be taken by patients with an
active pathological bleed
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Rivaroxaban dose is dependent on indication and renal
function.
Atrial fibrillation: CrCl > 50ml/min – 20mg po once daily,
CrCl 15-50 ml/min – 15mg po once daily
Give with the evening meal.
Prophylaxis of DVT following hip or knee replacement
surgery: 10mg po once daily (if CrCl > 30ml/min)
Treatment of DVT/PE: 15mg twice daily with food x 21 days,
then 20mg po once daily with food for remaining treatment
(if CrCl > 30ml/min)
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To reduce the risk of stroke or systemic embolism in patients
with nonvalvular atrial fibrillation:
Dose is 5mg po BID
In patients with 2 of the following characteristics:
age > 80 yrs
body weight < or equal to 60kg
SCr > or equal to 1.5 mg/dl
Dose is 2.5 mg po BID
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Factor Xa Inhibitors can cause serious and potentially fatal
bleeding. Bleeding risk increases with age and decrease renal
function
Thrombosis may occur with abrupt discontinuation
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Patient to be provided with a copy of the appropriate “Xarelto
Medication Guide” or “Eliquis Medication Guide” and verbal
information about medication
The following points should be reviewed with patient/family:
 Take as prescribed
 Remind patient not to discontinue medication without talking to MD
(increased risk of thrombosis)
 Purpose of therapy & compliance
 Administration (rivaroxaban doses 15mg and above are to be given with food) and dosing
(missed doses)
 Monitor for signs of bleeding or thrombosis
 Communicate use of rivaroxaban or apixaban to other healthcare
professionals
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o
o
o
o
Which of the following is a direct thrombin
inhibitor?
Enoxaparin (Lovenox)
Apixaban (Eliquis)
Dabigatran (Pradaxa)
Rivaroxaban (Xarelto)

Dabigatran (Pradaxa) is a direct thrombin
inhibitor. It’s only indication is in preventing
stroke or systemic embolism in patients with
nonvalvular atrial fibrillation
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o
o
o
o
Which of the following medications listed below has multiple
indications for use including treatment of PE/DVT, prevention
of PE/DVT in total hip/knee replacements, and prevention of
stroke & systemic embolism in patients with nonvalvular atrial
fibrillation?
Rivaroxaban (Xarelto)
Dabigatran (Pradaxa)
Apixaban (Eliquis)
Argatroban

Xarelto has FDA approval for use in multiple
indications.
The End

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