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Page 1: PE and DVT

PE and DVTPE and DVT

Page 2: PE and DVT

Pathogenesis of VTPathogenesis of VT

Virchow’s triad:Virchow’s triad:– Damage to vessel wallDamage to vessel wall– Venous stasisVenous stasis– Hypercoagulability Hypercoagulability

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SourceSource

Most PE’s originate from thrombi in the deep Most PE’s originate from thrombi in the deep venous system of the legs, although they may venous system of the legs, although they may also originate in the pelvic, renal or upper also originate in the pelvic, renal or upper extremity veins. extremity veins. HOWEVER, less than 30% of pts will have HOWEVER, less than 30% of pts will have symptoms in their legs at the time of diagnosis of symptoms in their legs at the time of diagnosis of PEPE20% of calf vein thrombi propagate above the 20% of calf vein thrombi propagate above the popliteal fossa. popliteal fossa. 20% of lower extremity venous emboli begin in 20% of lower extremity venous emboli begin in the proximal veins without prior calf involvement. the proximal veins without prior calf involvement.

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Acquired Risk FactorsAcquired Risk Factors

AgeAgePrevious thrombosisPrevious thrombosisImmobilizationImmobilizationMajor surgery – especially OrthoMajor surgery – especially OrthoEstrogen – OCP, HRT, SERMsEstrogen – OCP, HRT, SERMsAntiphospholipid Ab syndromeAntiphospholipid Ab syndromeMalignancyMalignancyNephrotic syndromeNephrotic syndromeInflammatory bowel diseaseInflammatory bowel diseaseMyeloproliferative d/o – esp p. vera and ETMyeloproliferative d/o – esp p. vera and ETPNHPNHLong distance air travelLong distance air travelHITHIT

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Inherited Risk FactorsInherited Risk Factors

Factor V Leiden mutationFactor V Leiden mutation

G20210A prothrombin gene mutationG20210A prothrombin gene mutation

Antithrombin deficiencyAntithrombin deficiency

Protein C or S deficiencyProtein C or S deficiency

DysfibrinogenemiaDysfibrinogenemia

HyperhomocysteinemiaHyperhomocysteinemia

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PresentationPresentation

DyspneaDyspneaPleuritic chest painPleuritic chest painCough +/- hemoptysisCough +/- hemoptysisOn exam may have On exam may have

TachypneaTachypneaTachycardiaTachycardiaS4S4Loud P2Loud P2May have fever – rarely >102May have fever – rarely >102In massive PE can have hypotension and shockIn massive PE can have hypotension and shock

Look at legs for swelling and Homan’s sign – but Look at legs for swelling and Homan’s sign – but only helpful if positive. only helpful if positive.

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Homan’s SignHoman’s Sign

Passive dorsiflexion of the foot with the Passive dorsiflexion of the foot with the knee straight may give pain in the calf and knee straight may give pain in the calf and back of the knee when there is a deep back of the knee when there is a deep venous thrombosis. venous thrombosis.

Some concern that vigorous dorsiflexion of Some concern that vigorous dorsiflexion of the foot can expel clot from the veins and the foot can expel clot from the veins and so this test may have its dangers. so this test may have its dangers.

The sign is not specific for DVTThe sign is not specific for DVT

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DDX swollen calfDDX swollen calf

DVTDVTBakers CystBakers CystCellulitisCellulitisGout – if really bad it can sometimes look Gout – if really bad it can sometimes look like a cellulitislike a cellulitisIf bilateral think about CHF, Nephrotic If bilateral think about CHF, Nephrotic syndrome, liver failure, venous syndrome, liver failure, venous insufficiency, pregnancy or pelvic mass, insufficiency, pregnancy or pelvic mass, vasodilators esp nifedipinevasodilators esp nifedipine

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ABGABG

Usually shows hypoxia, hypocapnia, respiratory alkalosisUsually shows hypoxia, hypocapnia, respiratory alkalosisA-a gradient:A-a gradient:

Normal 7-14 depending on ageNormal 7-14 depending on ageIncreases with age, FiO2 and supine postureIncreases with age, FiO2 and supine postureEstimate of normal for age: Estimate of normal for age:

– Age/4 +4Age/4 +4

A-a gradient = (FiO2 x713 – pCO2/0.8) – PaO2A-a gradient = (FiO2 x713 – pCO2/0.8) – PaO2

If A-a gradient normal, PaO2 <80, Pa CO2 >45 then If A-a gradient normal, PaO2 <80, Pa CO2 >45 then hypoventilation accounts for hypoxiahypoventilation accounts for hypoxiaIncreased A-a gradient occurs in V/Q mismatch, Increased A-a gradient occurs in V/Q mismatch, shunting and any kind of barrier to diffusion (e.g. shunting and any kind of barrier to diffusion (e.g. pulmonary edema)pulmonary edema)BUT can be normal and still have PE!BUT can be normal and still have PE!

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LabsLabs

Troponin, LDH, AST and BNP may all be Troponin, LDH, AST and BNP may all be elevatedelevated

Check baseline CBC, PT/PTT/INR, CrCheck baseline CBC, PT/PTT/INR, Cr

D-dimer D-dimer Normal D-dimer excludes PE, but positive D-Dimer Normal D-dimer excludes PE, but positive D-Dimer is not helpful (as it can be positive in many is not helpful (as it can be positive in many conditions including sepsis, immobility, post Sx and conditions including sepsis, immobility, post Sx and CAP)CAP)

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EKGEKG

May have non specific ST and T wave changesMay have non specific ST and T wave changes

““Typical” SI, QIII, TIII - rare. Typical” SI, QIII, TIII - rare.

Sinus tachycardiaSinus tachycardia

T wave inversions in right to mid chest leadsT wave inversions in right to mid chest leads

Poor R wave progression (acute RV dilation)Poor R wave progression (acute RV dilation)

P pulmonaleP pulmonale

RV conduction delaysRV conduction delays

Right axis shiftRight axis shift

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CXRCXR

May have area of atelectasisMay have area of atelectasis

May have wedge shaped infarct May have wedge shaped infarct peripherallyperipherally

Pleural effusion occurs in about 40%Pleural effusion occurs in about 40%

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DVT – D-DimerDVT – D-Dimer

Fibrin degradation product elevated in active Fibrin degradation product elevated in active thrombosisthrombosis

Negative test can help exclude VTENegative test can help exclude VTE

Preferred testPreferred test– Quantitative Rapid ELISA – sensitivity 96/95% for Quantitative Rapid ELISA – sensitivity 96/95% for

DVT/PEDVT/PE– Other methods include latex agglutination and RBC Other methods include latex agglutination and RBC

agglutination (SimpliRED)agglutination (SimpliRED)

Stein PD, Hull RD, Patel KC, et al. D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review. Ann Int Med. 2004;140(8):589-602

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DVT – D-DimerDVT – D-Dimer

In 283 patients with In 283 patients with suspected DVT, low-suspected DVT, low-moderate Wells DVT moderate Wells DVT score and negative d-score and negative d-dimer only 1 (NPV dimer only 1 (NPV 99.6%) had DVT over 99.6%) had DVT over next 3 monthsnext 3 months

Bates SM, Kearon C, Crowther M, et al. Ann Intern Med. 2003;138:787-94

• Sensitive d-dimer testing can rule out DVT in low-moderate risk patients

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Doppler US of lower extremitiesDoppler US of lower extremities

If high clinical suspicion should be If high clinical suspicion should be repeated 7-10 days after initial scan as repeated 7-10 days after initial scan as below knee DVT can propagatebelow knee DVT can propagate

Also remember that some pt develop Also remember that some pt develop DVT’s elsewhere – so you may not find a DVT’s elsewhere – so you may not find a DVT in their legs if the source was their DVT in their legs if the source was their arm!arm!

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PE – Assigning Pretest ProbabilityPE – Assigning Pretest Probability

Single most important step in the diagnosis of Single most important step in the diagnosis of pulmonary embolismpulmonary embolismMay be done based on clinical judgment or May be done based on clinical judgment or aided by a clinical scoring systemaided by a clinical scoring systemModified Wells Criteria is the most widely used Modified Wells Criteria is the most widely used and studiedand studiedReliably stratifies patients by likelihood of PE to Reliably stratifies patients by likelihood of PE to allow selection of safe (<2% VTE risk if no allow selection of safe (<2% VTE risk if no anticoagulation) management strategyanticoagulation) management strategy

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DVT – Wells ScoreDVT – Wells Score

CancerCancerParalysis or plaster Paralysis or plaster immobilizationimmobilizationBedrest > 3d or surgery Bedrest > 3d or surgery in past 4 wksin past 4 wksLocalized tendernessLocalized tenderness

Entire leg swollenEntire leg swollenCalf > 3cm larger than Calf > 3cm larger than unaffected legunaffected legPitting edema greater Pitting edema greater than unaffected legthan unaffected legCollateral superficial Collateral superficial veinsveins

The following were assigned a point value of 1 if present:

• Alternative diagnosis more likely than DVT = - 2 points• Probability High (≥ 3), Moderate (1-2) or Low (0 or less)• DVT risk: High – 75%, Moderate – 17%, Low – 3%

Wells PS, Andersen DR, Bormanis J et al. Lancet. 1997;350:1795-8

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PE – Imaging StudiesPE – Imaging Studies

PIOPED study quantified the value of V/Q scans PIOPED study quantified the value of V/Q scans in diagnosing PEin diagnosing PE– Normal/near-normal scans exclude PE in low-Normal/near-normal scans exclude PE in low-

moderate risk patientsmoderate risk patients– High probability scans confirm PE in moderate-high High probability scans confirm PE in moderate-high

risk patientsrisk patients– Drawbacks: more difficult test and 73% patients had Drawbacks: more difficult test and 73% patients had

indeterminate scansindeterminate scans

LE compression US showing DVT helps LE compression US showing DVT helps diagnostically, but a negative study insufficient diagnostically, but a negative study insufficient to exclude VTEto exclude VTE

PIOPED Study. JAMA. 1990;263(20):2753-59

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Clinical Models to Assess PE RiskClinical Models to Assess PE RiskPIOPED Criteria – Correlates well with incidence of PEPIOPED Criteria – Correlates well with incidence of PE

Based entirely of clinician impression, not clinical risk factorsBased entirely of clinician impression, not clinical risk factors

Pretest Clinical Gestalt Pretest Clinical Gestalt of PE Probability of PE Probability

Actual PE Rate on PA Actual PE Rate on PA AngiogramAngiogram

Low (“<20%” should Low (“<20%” should have PE) have PE)

9% 9%

Intermediate (“20-79%” Intermediate (“20-79%” should have PE) should have PE)

30% 30%

High (“80-100%” should High (“80-100%” should have PE) have PE)

68% 68%

PIOPED Investigators. JAMA 1990; 263: 2753-2759.

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PE – Helical CT (CTA)PE – Helical CT (CTA)

Eng performed a systematic review (SR) of all studies & Eng performed a systematic review (SR) of all studies & SRs on CTA prior to 2003SRs on CTA prior to 2003– Only 1/6 SRs and 3/8 primary studies found CTA >90% sensitive Only 1/6 SRs and 3/8 primary studies found CTA >90% sensitive

for PEfor PE

In a similar SR in 2005 Roy concludedIn a similar SR in 2005 Roy concluded– Negative CTA could safely exclude PE in low risk patientsNegative CTA could safely exclude PE in low risk patients– Negative LE US plus negative CTA could exclude PE in Negative LE US plus negative CTA could exclude PE in

moderate risk patientsmoderate risk patients

At the time of those SRs no studies of faster At the time of those SRs no studies of faster multidetector CTA (MDCT) were availablemultidetector CTA (MDCT) were available

Eng J, Krishnan JA, Segal JB, et al. AJR 2004;183(6):1819-27. Roy PM, Colombet I, Durieux P, et al. BMJ 2005;331(7511):259.

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PE – PIOPED IIPE – PIOPED IIPublished June 2006 in NEJMPublished June 2006 in NEJM– 1090 consecutive patients with suspected PE1090 consecutive patients with suspected PE– All given Modified Wells ScoreAll given Modified Wells Score– MDCT - mostly 4 sliceMDCT - mostly 4 slice– Gold standard – composite - V/Q, angiogram & Gold standard – composite - V/Q, angiogram &

LE USLE US

FindingsFindings– MDCT: sens 83% & spec 96% for PEMDCT: sens 83% & spec 96% for PE– Positive predictive value >90% in Positive predictive value >90% in

moderate/high riskmoderate/high risk– Negative predictive value 96% in low risk Negative predictive value 96% in low risk

patients but only 89% in moderate risk patientspatients but only 89% in moderate risk patients

Findings generally consistent with Roy’s Findings generally consistent with Roy’s SRSR

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V/Q scanningV/Q scanning

Look for evidence of ventilation perfusion Look for evidence of ventilation perfusion mismatchmismatch

Can only really be done if pt has normal CXRCan only really be done if pt has normal CXR

Normal scan virtually excludes PE even if Normal scan virtually excludes PE even if pretest clinical probability was felt to be high. pretest clinical probability was felt to be high.

If a patient with intermediate clinical probability If a patient with intermediate clinical probability of PE has an intermediate scan then need of PE has an intermediate scan then need further testingfurther testing

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A 60-year-old man with asthma is evaluated in the emergency A 60-year-old man with asthma is evaluated in the emergency department because of the acute onset of chest pain while lifting a department because of the acute onset of chest pain while lifting a heavy object. The pain is sharp and accentuated by deep breathing heavy object. The pain is sharp and accentuated by deep breathing and by movement of the upper extremities. It is located over the left and by movement of the upper extremities. It is located over the left precordium. precordium.

The physical examination and chest x-ray are normal. A ventilation-The physical examination and chest x-ray are normal. A ventilation-perfusion lung scan shows matched areas of perfusion and perfusion lung scan shows matched areas of perfusion and ventilation. ventilation.

Which one of the following is the correct interpretation of the Which one of the following is the correct interpretation of the ventilation-perfusion lung scan?ventilation-perfusion lung scan?( A ) Normal( A ) Normal( B ) Low probability( B ) Low probability( C ) Indeterminate( C ) Indeterminate( D ) High probability( D ) High probability

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Correct Answer = Correct Answer = AA

The lung scan is normal, with matched perfusion and The lung scan is normal, with matched perfusion and ventilation. This lung scan rules out a pulmonary ventilation. This lung scan rules out a pulmonary embolism, and another source for the chest pain should embolism, and another source for the chest pain should be sought. Often asthma does complicate the be sought. Often asthma does complicate the interpretation of the lung scan, but the problem relates to interpretation of the lung scan, but the problem relates to matched defects in which the airway obstruction matched defects in which the airway obstruction decreases the ventilation to an area of the lung. The decreases the ventilation to an area of the lung. The consequent hypoxia in that area leads to reduction in consequent hypoxia in that area leads to reduction in blood flow in the same area. These areas are rarely blood flow in the same area. These areas are rarely segmental. segmental.

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Spiral CT/CT angiogramSpiral CT/CT angiogram

Used if CXR not normalUsed if CXR not normal

Picks up large central emboli but is less Picks up large central emboli but is less sensitive for the smaller peripheral emboli. sensitive for the smaller peripheral emboli.

True pulmonary angiography rarely used True pulmonary angiography rarely used now, though can do direct thrombolysis in now, though can do direct thrombolysis in massive PE.massive PE.

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EchoEcho

More than 80% of pts with PE will have More than 80% of pts with PE will have abnormalities of RV size or function, or TR.abnormalities of RV size or function, or TR.

McConnells sign – regional wall motion McConnells sign – regional wall motion abnormalities that spare the R ventricular apex abnormalities that spare the R ventricular apex are very suggestive of PEare very suggestive of PE

BUT echo is only really used for Dx of massive BUT echo is only really used for Dx of massive lifethreatening PE’s when rapid diagnosis is lifethreatening PE’s when rapid diagnosis is needed to determine whether thrombolysis needed to determine whether thrombolysis should be given.should be given.

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TreatmentTreatment

Identify any contraindications to Identify any contraindications to anticoagulations – if yes then IVC filteranticoagulations – if yes then IVC filterInquire about h/o HITInquire about h/o HIT

If yes, then use direct thrombin inhibitorIf yes, then use direct thrombin inhibitor

Assess need for hospitalizationAssess need for hospitalizationExtensive iliofemoral DVT with circ compromiseExtensive iliofemoral DVT with circ compromiseIncreased risk of bleedingIncreased risk of bleedingLimited cardioresp reserveLimited cardioresp reservePoor compliancePoor complianceCI to LMW heparinCI to LMW heparin

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TreatmentTreatment

Administer LMW heparin or unfractionated Administer LMW heparin or unfractionated heparinheparin

Goal 1.5-2.5 x PTT in first 24 hoursGoal 1.5-2.5 x PTT in first 24 hours

Check platelet count on day 3-5Check platelet count on day 3-5

Treat at least five days and until patient’s Treat at least five days and until patient’s INR is >2 on coumadin for two INR is >2 on coumadin for two consecutive daysconsecutive days

Start coumadin on day 1Start coumadin on day 1

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Treatment DurationTreatment Duration

3-6 months in most patients3-6 months in most patientsIndefinite treatment:Indefinite treatment:– >1 spontaneous event>1 spontaneous event– One spontaneous life threatening eventOne spontaneous life threatening event– Antiphospholipid syndromeAntiphospholipid syndrome– Antithrombin deficiencyAntithrombin deficiency– >1 genetic allelic abnormality>1 genetic allelic abnormality

– Homozygote for Factor V Leiden or prothrombin gene mutationHomozygote for Factor V Leiden or prothrombin gene mutation– Heterozygote for bothHeterozygote for both

– Protein C/S deficiencyProtein C/S deficiency– Continuing RF especially active advanced CAContinuing RF especially active advanced CA

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Contraindications to Contraindications to AnticoagulationAnticoagulation

AbsoluteAbsolute– Active bleedingActive bleeding– Severe bleeding diathesisSevere bleeding diathesis– Platelet count <20Platelet count <20– Neurosurgery, ocular surgery or intracranial Neurosurgery, ocular surgery or intracranial

bleeding within the past 10 daysbleeding within the past 10 days

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Contraindications to Contraindications to AnticoagulationAnticoagulation

RelativeRelative– Mild/moderate bleeding diathesis or Mild/moderate bleeding diathesis or

thrombocytopeniathrombocytopenia– Brain metsBrain mets– Major abdominal surgery within 2 daysMajor abdominal surgery within 2 days– GI or GU bleeding within 14 daysGI or GU bleeding within 14 days– EndocarditisEndocarditis– Severe HTN (SBP >200, DBP > 120)Severe HTN (SBP >200, DBP > 120)

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Inferior Vena Cava FilterInferior Vena Cava Filter

Reduce risk of PE but carry increased risk Reduce risk of PE but carry increased risk of DVTof DVT

Use in pts with DVT who cannot take Use in pts with DVT who cannot take anticoagulation e.g. due to bleeding riskanticoagulation e.g. due to bleeding risk

Also used with or without anticoagulation Also used with or without anticoagulation in patients with high risk of death should in patients with high risk of death should further PE occur. further PE occur.

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Hypercoagulation WorkupHypercoagulation Workup

Test all patients for unprovoked VT for Test all patients for unprovoked VT for antiphospholipid ab syndrome and antiphospholipid ab syndrome and hyperhomocysteinemiahyperhomocysteinemia

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Hypercoagulation WorkupHypercoagulation Workup

Test for Factor V Leiden, prothrombin gene Test for Factor V Leiden, prothrombin gene mutation and deficiencies of antithrombin, mutation and deficiencies of antithrombin, protein C/S in the following patients:protein C/S in the following patients:

Family h/o VTFamily h/o VT

VT before the age of 50VT before the age of 50

Recurrent VTRecurrent VT

Thrombosis in an unusual site (mesenteric, renal, cerebral, Thrombosis in an unusual site (mesenteric, renal, cerebral, hepatic)hepatic)

Heparin resistance (antithrombin deficiency)Heparin resistance (antithrombin deficiency)

Warfarin induced skin necrosis (protein C/S def)Warfarin induced skin necrosis (protein C/S def)

Neonatal purpura fulminansNeonatal purpura fulminans

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Hypercoagulation WorkupHypercoagulation Workup

Wait to check for deficiency in Wait to check for deficiency in antithrombin, protein C or S until 2 weeks antithrombin, protein C or S until 2 weeks after anticoagulation rx is completedafter anticoagulation rx is completed

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VTE – Prevention UnderutilizedVTE – Prevention Underutilized

DVT-FREE DVT-FREE prospective prospective registry of 5,451 registry of 5,451 patients at 183 patients at 183 US hospitalsUS hospitals

Only 32% of Only 32% of medical patients medical patients with DVT with DVT received DVT received DVT prophylaxisprophylaxis

0

5

10

15

20

25

30

35

40

45

US 1991 US 2001 Canada2002

UK 2005

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VTE – Prophylaxis in Medical VTE – Prophylaxis in Medical PatientsPatients

IndicationsIndications– CHF or severe respiratory diseaseCHF or severe respiratory disease

– Bedrest with additional risk factorBedrest with additional risk factorCancerCancer

Prior VTEPrior VTE

– Most ICU patientsMost ICU patients

OptionsOptions– Low dose unfractionated heparin or LMWHLow dose unfractionated heparin or LMWH

– Sequential compression devicesSequential compression devices

– Graduated compression stockingsGraduated compression stockings

•Acute neurologic disease•Inflammatory bowel disease


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