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AcuteAcute PulmonaryPulmonary EmbolismEmbolism inin thethe CriticalCritical CareCare Unit:Unit: IsIs itit differentdifferent ??

KennethKenneth V.V. LeeperLeeper Jr.Jr. MDMD AssociateAssociate ProfessorProfessor ofof MedicineMedicine DivisionDivision ofof Pulmonary,Pulmonary, AllergAllergyy andand CriticalCritical CareCare MedicineMedicine EmoryEmory SchoolSchool ofof MedicineMedicine Atlanta,Atlanta, GeorgiaGeorgia

AcuteAcute PulmonaryPulmonary EmbolismEmbolism inin thethe CriticalCritical CareCare Unit:Unit: IsIs itit differentdifferent ??

CaseCase PresentationPresentation TheThe incidenceincidence ofof VTEVTE inin MICUMICU patientspatients ClinicalClinical CluesClues ofof VTEVTE inin MICUMICU PatientsPatients TreatmentTreatment ofof VTEVTE inin CriticallyCritically –– IllIll PatientsPatients ImpactImpact ofof currentcurrent prophylaxisprophylaxis onon thethe preventionprevention ofof DVTDVT inin MICUMICU patientspatients

AcuteAcute PulmonaryPulmonary EmbolismEmbolism inin thethe CriticalCritical CareCare Unit:Unit: IsIs itit differentdifferent ??

CaseCase PresentationPresentation TheThe RiskRisk FactorFactor andand IncidenceIncidence ofof VTEVTE inin MICUMICU patientspatients ClinicalClinical CluesClues ofof VTEVTE inin MICUMICU PatientsPatients ImpactImpact ofof currentcurrent prophylaxisprophylaxis onon thethe preventionprevention ofof DVTDVT inin MICUMICU patientspatients

VTEVTE inin thethe ICUICU CaseCase StudyStudy

5858--yy--oo AAMAAM presentedpresented toto thethe MICUMICU withwith aa RMLRML andand RLLRLL pneumoniapneumonia PatientPatient requiredrequired 100%100% nonnon--rebreatherrebreather toto maintainmaintain OO 22 saturationsaturation >> 90%90% PMH:PMH: HistoryHistory ofof rightright lowerlower extremityextremity DVTDVT afterafter aa longlong carcar drivedrive 88 yearsyears PTAPTA NoNo medications,medications, nono allergiesallergies

VTEVTE inin thethe ICUICU CaseCase StudyStudy

PhysicalPhysical examexam

WeightWeight 112112 kg,kg, RRRR 36,36, BPBP 142/78142/78 mmmm Hg,Hg, TT 38.738.7 °°C,C, egophonyegophony rightright posteriorposterior chest,chest, 2/62/6 SEM;SEM; restrest ofof examexam unremarkableunremarkable

OO 22 satsat 91%91% onon 100%100% NRMNRM Labs:Labs: WBCWBC 15,60015,600 (84(84 PMNs,PMNs, 1010 bands)bands) CXR:CXR: RML/RLLRML/RLL pneumoniapneumonia InitialInitial Rx:Rx: ceftriaxoneceftriaxone // azithromycinazithromycin DVTDVT prophylaxis:prophylaxis: UFHUFH 5,0005,000 SCSC qq 88 hh

VTEVTE inin thethe ICUICU CaseCase StudyStudy

MICUMICU coursecourse

PatientPatient requiredrequired faceface maskmask veventilationntilation withwith BiPAPBiPAP forfor 4848 hourshours thenthen weanedweaned toto 50%50% VenturiVenturi maskmask DayDay 4:4: persistentpersistent feverfever withwith episodeepisode ofof hypotensionhypotension thatthat respondedresponded toto fluidfluid therapytherapy DayDay 5:5: persistentpersistent fever,fever, WBCWBC normalizing;normalizing; LELE DopplersDopplers obtained:obtained: rightright proximalproximal LELE DVTDVT →→ RxRx withwith weightweight--basedbased UFHUFH EveningEvening ofof dayday 5:5: episodeepisode ofof hypotensionhypotension requiringrequiring fluidsfluids andand briefbrief vasopressorvasopressor therapytherapy →→ spiralspiral CTCT scanscan ofof thethe chestchest obtainedobtained

VTEVTE inin thethe ICUICU CaseCase StudyStudy

SpiralSpiral CTCT scanscan ofof thethe chestchest –– largelarge bilateralbilateral PEPE BothBoth troponintroponin andand BNPBNP elevatedelevated CardiologyCardiology fellowfellow performedperformed echocardiogram:echocardiogram: SevereSevere RVRV enlargementenlargement withwith RVRV wallwall motionmotion abnormalitiesabnormalities ManagementManagement options?options?

AcuteAcute PulmonaryPulmonary EmbolismEmbolism inin thethe CriticalCritical CareCare Unit:Unit: IsIs itit differentdifferent ??

CaseCase PresentationPresentation TheThe RiskRisk FactorFactor andand IncidenceIncidence ofof VTEVTE inin MICUMICU patientspatients DiagnosisDiagnosis ofof VTEVTE inin MICUMICU PatientsPatients ImpactImpact ofof currentcurrent prophylaxisprophylaxis onon thethe preventionprevention ofof DVTDVT inin MICUMICU patientspatients

TheThe ChallengeChallenge ofof VTEVTE inin CriticallyCritically IllIll PatientsPatients

CriticallyCritically illill patientspatients commonlycommonly developdevelop DVTDVT RateRate variesvaries fromfrom 2222 –– 60%60% dependingdepending onon patientpatient characteristicscharacteristics MethodsMethods ofof prophylaxisprophylaxis areare notnot universaluniversal InIn highhigh--riskrisk groupsgroups moremore effectiveeffective prophylaxisprophylaxis regimensregimens areare neededneeded

ClinicalClinical RiskRisk FactorsFactors forfor VTEVTE inin CriticallyCritically IllIll PatientsPatients

FactorsFactors beforebefore ICUICU admissionadmission

AdditionalAdditional factorsfactors acquiredacquired inin ICUICU

RecentRecent surgerysurgery

Trauma,Trauma, burnsburns

MalignancyMalignancy andand treatmenttreatment

SepsisSepsis

ImmobilizationImmobilization // bedbed rest,rest,

stroke,stroke, spinalspinal cordcord injuryinjury IncreasingIncreasing ageage

HeartHeart // respiratoryrespiratory failurefailure

PreviousPrevious VTEVTE

PregnancyPregnancy // puerperiumpuerperium

EstrogensEstrogens

CentralCentral venousvenous lineslines

SepsisSepsis

PharmacologicPharmacologic interventions:interventions:

sedation,sedation, paralysisparalysis MechanicalMechanical ventilationventilation

An autopsy study revealed that 20% of patients who died in the ICU had evidence of PE. Moser KM. JAMA 1981.

PrevalencePrevalence ofof ofof DVTDVT AmongAmong PatientsPatients inin thethe MICUMICU

UltrasoundUltrasound inin 100100 patientspatients admittedadmitted toto MICUMICU forfor >> 4848 hourshours IncidenceIncidence ofof DVTDVT –– 33%33% 61%61% receivedreceived DVTDVT prophylaxisprophylaxis PatientsPatients withwith DVTDVT –– moremore likelylikely toto havehave aa historyhistory priorprior VTEVTE HospitalHospital MRMR –– 36%36% w/w/ DVTDVT vs.vs. 24%24% w/ow/o DVTDVT ((PP ==

0.028)0.028)

HirschHirsch DR,DR, etet al.al. JAMAJAMA 1995;274:3351995;274:335--7.7.

VTEVTE onon PresentationPresentation toto thethe ICUICU

ProspectiveProspective studystudy ofof 196196 COPDCOPD patientspatients admittedadmitted toto aa respiratoryrespiratory ICUICU UltrasoundUltrasound onon dayday ofof admissionadmission 21/19621/196 (11%)(11%) hadhad DVT,DVT, allall aboveabove thethe kneeknee 18/2118/21 asymptomaticasymptomatic NoNo differencesdifferences inin age,age, ABG,ABG, FEVFEV 11 ,, oror dyspneadyspnea PhysicalPhysical examexam notnot helpfulhelpful toto detectdetect DVTDVT

SchonhoferSchonhofer B,B, KohlerKohler D.D. RespirationRespiration 1998;65:1751998;65:175--7.7.

VTEVTE inin DecompensatedDecompensated CHFCHF patientspatients requiringrequiring CCUCCU admissionadmission

198198 patientspatients admittedadmitted withwith severesevere decompensateddecompensated CHFCHF overover 3131 monthmonth periodperiod 18/19818/198 –– acuteacute PEPE // 88 ofof 1818 (44.4%)(44.4%) DVTDVT Thromboprophylaxis:Thromboprophylaxis: 12/1812/18 (66.7%)(66.7%) vsvs 126/180126/180 (70%)(70%) NSNS IndependentIndependent riskrisk factorsfactors associatesassociates withwith PEPE

CancerCancer RVRV abnabn Prev.Prev. VTEVTE

OROR 26.926.9 OROR 9.79.7 OROR 9.19.1

Darze ES.et.al. Chest 2005; 128;2576 - 2580

DVTDVT inin medicalmedical--surgicalsurgical criticallycritically illill patients:patients:

prevalence,prevalence, incidenceincidence andand riskrisk factors.factors. CookCook DD et.al.et.al. Crit.Crit. CareCare Med.Med. 20052005 33:156533:1565--7171 ProspectiveProspective cohortcohort studystudy closedclosed universityuniversity affiliatedaffiliated ICUICU ConsecutiveConsecutive patientspatients enrolled,enrolled, excludedexcluded trauma,trauma, orthopedicorthopedic surgery,surgery, pregnancypregnancy andand lifelife supportsupport withdrawnwithdrawn BilateralBilateral LELE USUS withinwithin 4848 hrshrs ofof admissionadmission andand twicetwice weeklyweekly andand ifif DVTDVT waswas suspectedsuspected ThromboprophylaxisThromboprophylaxis waswas protocolprotocol directeddirected andand universaluniversal

DVTDVT inin medicalmedical--surgicalsurgical criticallycritically illill patients:patients:

prevalence,prevalence, incidenceincidence andand riskrisk factors.factors. CookCook DD et.al.et.al. Crit.Crit. CareCare Med.Med. 20052005 33:156533:1565--7171

261261 patientspatients withwith APIIAPII ofof 25.525.5 PrevalencePrevalence ofof DVTDVT onon admissionadmission –– 2.7%2.7% IncidenceIncidence overover thethe ICUICU staystay –– 9.6%9.6% IndependentIndependent riskrisk factorsfactors forfor DVTDVT

PersonalPersonal oror FHFH ofof VTEVTE –– HRHR 4.04.0 ESRDESRD –– HRHR 3.73.7 PlateletPlatelet transfusionstransfusions –– HRHR 3.23.2 VasopressorVasopressor useuse –– HRHR 2.82.8

Consequences of DVT Longer ICU stay p=0.0 Longer duration on MV Longer hospitalization

DeepDeep VeinVein ThrombosisThrombosis DuringDuring ProlongedProlonged MechanicalMechanical VentilationVentilation DespiteDespite ProphylaxisProphylaxis

IbrahimIbrahim EH,EH, IreguiIregui M,M, PrenticePrentice D,D, ShermanSherman G,G, KollefKollef M,M, ShannonShannon WW

CriticalCritical CareCare Medicine.Medicine. 2002;30:7712002;30:771--4.4.

Objective: Determine the prevalence of DVT among patients requiring prolonged mechanical ventilation in the ICU

DVTDVT DuringDuring ProlongedProlonged MechanicalMechanical VentilationVentilation DespiteDespite ProphylaxisProphylaxis

MeasurementsMeasurements

TotalTotal ofof 110110 patientspatients requiringrequiring mechanicalmechanical ventilationventilation forfor >> 77 daysdays werewere enrolledenrolled ProphylaxisProphylaxis againstagainst DVTDVT employedemployed inin 110110 patientspatients (100%)(100%) 2626 patientspatients (23.6%)(23.6%) developeddeveloped DVTDVT

IbrahimIbrahim EH,EH, etet al.al. CritCrit CareCare MedMed 2002;30:7712002;30:771--4.4.

DVTDVT DuringDuring ProlongedProlonged MechanicalMechanical VentilationVentilation DespiteDespite ProphylaxisProphylaxis

20 15 10 5 0 PercentPercent
20
15
10
5
0
PercentPercent

1234

WeekWeek DVTDVT detecteddetected

RiskRisk factorsfactors forfor DVTDVT UnderlyingUnderlying malignancymalignancy RenalRenal failurefailure GIGI disturbancesdisturbances DurationDuration ofof CVPCVP lineline

ClinicalClinical outcomesoutcomes PEPE –– moremore commoncommon withwith DVTDVT (11.5(11.5 vs.vs. 0.0%)0.0%) NoNo differencedifference inin LOSLOS oror

mortalitymortality

IbrahimIbrahim EH,EH, etet al.al. CritCrit CareCare MedMed 2002;30:7712002;30:771--4.4.

DVTDVT DuringDuring ProlongedProlonged MechanicalMechanical VentilationVentilation DespiteDespite ProphylaxisProphylaxis

IncidenceIncidence andand PreventionPrevention

90 80.8 80 73.1 70 60 50 40 26.9 30 19.2 20 10 0 PercentPercent
90
80.8
80
73.1
70
60
50
40
26.9
30
19.2
20
10
0
PercentPercent

UE-DVT

LE-DVT

UFH

SCD

IbrahimIbrahim EH,EH, etet al.al. CritCrit CareCare MedMed 2002;30:7712002;30:771--4.4.

PrevalencePrevalence ofof VTEVTE inin andand LTACLTAC Setting:Setting:

PreliminaryPreliminary Data.Data. VTEVTE LTACLTAC StudyStudy GroupGroup

SelectSelect LTACLTAC ECLH:ECLH: JulyJuly 11 20062006 –– JuneJune 13,13,

20072007

5050 admissionsadmissions toto thethe EmoryEmory PulmonaryPulmonary ServiceService 40/5040/50 hadhad screeningscreening USUS ofof thethe lowerlower extremitiesextremities andand upperupper extremitiesextremities (( ifif clinicallyclinically indicated)indicated) 6/406/40 (15%)(15%) -- VTEVTE eventsevents onon screeningscreening US.US. 44 LELE DVTDVT andand 22 UEUE DVTsDVTs

VasopressorVasopressor AdministrationAdministration MayMay PredisposePredispose ICUICU PatientsPatients toto DVTDVT

Multivariable analysis identified vasopressor administration as an independent risk factor (hazard ratio 2.8, 95% CI 1.1 - 7.2) for DVT

Patients*
Patients*

0 5

10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90

Days in ICU

Cook D et al. Crit Care Med. 2005;22:1565- 1571.

Days in ICUin ICU Cook D et al. Crit Care Med. 2005;22:1565- 1571. Vasopressors DVT *Patients (9 of

VasopressorsD et al. Crit Care Med. 2005;22:1565- 1571. Days in ICU DVT *Patients (9 of 261)

DVT

*Patients (9 of 261) who recevied vasopressors and developed DVT

VTEVTE inin SevereSevere Sepsis:Sepsis: IncidenceIncidence ofof VTEVTE inin SevereSevere sepsissepsis treatedtreated withwith DrotrecoginDrotrecogin alfaalfa withwith oror withoutwithout prophylacticprophylactic heparin.heparin. LevyLevy M.M. AbstractAbstract ChestChest 20062006

XpressXpress studystudy –– largelarge phasephase 3B3B 2828 dayday mortalitymortality andand thethe relativerelative incidenceincidence ofof VTEVTE inin patientspatients treatedtreated withwith drotrecogindrotrecogin alfaalfa (DAA)(DAA) withwith oror withoutwithout heparinheparin DecDec 20022002 –– JulyJuly 20052005

AdultAdult ptspts withwith highhigh riskrisk forfor severesevere sepsissepsis AllAll ptspts receivedreceived DAADAA StudyStudy drugs:drugs: heparinheparin 5000Usc5000Usc qq 1212 hrs,hrs, enoxaparinenoxaparin 40mg40mg scsc qdqd andand placeboplacebo Randomization:Randomization: 1:1:21:1:2 LowerLower extremityextremity USUS 44 andand 66 daysdays

VTEVTE inin SevereSevere Sepsis:Sepsis: IncidenceIncidence ofof VTEVTE inin SevereSevere sepsissepsis treatedtreated withwith DrotrecoginDrotrecogin alfaalfa withwith oror withoutwithout prophylacticprophylactic heparin.heparin. LevyLevy M.M. AbstractAbstract ChestChest 20062006

19351935 patientspatients werewere enrolledenrolled andand receivedreceived DAADAA andand oneone ofof thethe studystudy drugsdrugs

959959 placeboplacebo 976976 HeparinsHeparins (( 498498 UFH/478UFH/478 LMWH)LMWH)

IncidenceIncidence ofof VTEVTE StudyStudy periodperiod

heparinsheparins

placeboplacebo

pvaluepvalue

00--66 daysdays

4.6%4.6%

5.1%5.1%

0.60.6

00 –– 2828 daysdays

5.7%5.7%

7.0%7.0%

0.260.26

SubgroupsSubgroups withwith highesthighest incidenceincidence ofof VTE:VTE: previousprevious VTE,VTE, ageage >> 75,75, recentrecent surgery,surgery, ptspts onon baselinebaseline heparinheparin randomizedrandomized toto placeboplacebo VTEVTE incidenceincidence ––

8.1%8.1%

SourcesSources ofof Thrombi:Thrombi: CentralCentral VeinVein CatheterCatheter--RelatedRelated ThrombiThrombi inin thethe ICUICU

ProspectivelyProspectively performedperformed duplexduplex scansscans justjust beforebefore oror withinwithin 2424 hourshours afterafter removingremoving thethe IJIJ oror subclaviansubclavian CVLCVL inin ICUICU patientspatients

208208 lineslines studiedstudied MeanMean durationduration waswas 99 ±± 55 daysdays CatheterCatheter--relatedrelated clotclot –– 33%33% ofof patientspatients

TimsitTimsit JF,JF, etet al.al. ChestChest 1998:114;2071998:114;207--13.13.

WhatWhat isis thethe embolicembolic potentialpotential forfor UEUE-- DVT?DVT?

PE%

What What is is the the embolic embolic potential potential for for UE UE - -
What What is is the the embolic embolic potential potential for for UE UE - -
What What is is the the embolic embolic potential potential for for UE UE - -
What What is is the the embolic embolic potential potential for for UE UE - -
What What is is the the embolic embolic potential potential for for UE UE - -
What What is is the the embolic embolic potential potential for for UE UE - -
What What is is the the embolic embolic potential potential for for UE UE - -

SourcesSources ofof Thrombi:HITThrombi:HIT DiagnosisDiagnosis

SuspectSuspect ifif thethe plateletplatelet countcount dropsdrops belowbelow 150,000/mm150,000/mm 33 whilewhile patientpatient receivingreceiving UFHUFH oror LMWHLMWH SuspectSuspect ifif thethe plateletplatelet countcount dropsdrops 50%50% fromfrom prepre--heparinheparin baselinebaseline levelslevels SuspectSuspect ifif newnew thrombosisthrombosis whilewhile thethe patientpatient isis receivingreceiving UFHUFH oror LMWHLMWH SuspectSuspect ifif heparinheparin resistanceresistance developsdevelops ConfirmConfirm withwith laboratorylaboratory testtest (SRA,(SRA, HIPAHIPA oror ELISA)ELISA)

IncidenceIncidence ofof HITHIT andand VTEVTE AfterAfter UseUse ofof UFHUFH andand LMWHLMWH

LiteratureLiterature review:review: IdentifyIdentify studiesstudies usingusing UFHUFH oror LMWHLMWH forfor thromboprophylaxisthromboprophylaxis oror treatmenttreatment inin whichwhich newnew oror recurrentrecurrent VTEVTE andand serologicallyserologically confirmedconfirmed HITHIT 1010 studiesstudies

386386 ofof 6,2196,219 heparinheparin--treatedtreated patientspatients hadhad VTEVTE 3232 ofof 386386 VTEVTE patientspatients alsoalso hadhad HITHIT

AmongAmong 3232 casescases ofof HITHIT inin 386386 VTEVTE patientspatients

1717 casescases occurredoccurred inin 129129 IVIV UFHUFH--treatedtreated patientspatients (13.2%)(13.2%) 1414 casescases occurredoccurred inin 113113 SCSC UFHUFH--treatedtreated patientspatients (12.4%)(12.4%) 11 casecase occurredoccurred inin 144144 LMWHLMWH--treatedtreated patientspatients (0.7%)(0.7%)

LevineLevine RL,RL, etet al.al. ChestChest 2006;130:6812006;130:681--7.7.

AcuteAcute PulmonaryPulmonary EmbolismEmbolism inin thethe CriticalCritical CareCare Unit:Unit: IsIs itit differentdifferent ??

CaseCase PresentationPresentation TheThe RiskRisk FactorFactor andand IncidenceIncidence ofof VTEVTE inin MICUMICU patientspatients DiagnosisDiagnosis ofof VTEVTE inin MICUMICU PatientsPatients ImpactImpact ofof currentcurrent prophylaxisprophylaxis onon thethe preventionprevention ofof DVTDVT inin MICUMICU patientspatients

ClinicalClinical SymptomsSymptoms andand SignsSigns ofof VTEVTE inin MICUMICU PatientsPatients

NonspecificNonspecific PersistentPersistent FeverFever InIn MVMV patients,patients, unexplainedunexplained increaseincrease inin minuteminute ventilationventilation ETET CO2CO2 measurementmeasurement InIn MVMV patientspatients –– ParadoxicalParadoxical hypercarbiahypercarbia

NeitherNeither baselinebaseline teststests ofof molecularmolecular hypercoagulabilityhypercoagulability nornor DD--dimerdimer levelslevels predictpredict DVTDVT inin criticallycritically illill medicalmedical surgicalsurgical patientspatients PredictingPredicting patientspatients whowho areare harboringharboring asymptomaticasymptomatic DVTDVT oror PEPE isis aa desirabledesirable clinicalclinical goalgoal ProspectiveProspective studystudy ofof 197197 patientspatients inin aa medmed-- surgsurg ICUICU 66 commercialcommercial DD--dimerdimer testtest andand markersmarkers ofof hypercoagulabiltyhypercoagulabilty Conclusion:Conclusion: NoneNone ofof thethe testtest patientspatients atat riskrisk forfor DVTDVT

WhichWhich diagnosticdiagnostic teststests forfor VTEVTE evaluationevaluation inin thethe ICUICU patients?patients?

DependsDepends uponupon clinicalclinical stabilitystability andand renalrenal function.function. SuspectSuspect VTEVTE

ClinicallyClinically stablestable ++ normalnormal renalrenal functionfunction oror ESRD:ESRD: SpiralSpiral CTCT scanscan ofof thethe chestchest andand eithereither CTVCTV oror DopplerDoppler USUS thethe extremitiesextremities ClinicallyClinically stablestable ++ ongoingongoing renalrenal insufficency:insufficency: USUS ofof thethe extremitiesextremities andand TTE/TEETTE/TEE ClinicallyClinically unstableunstable –– unableunable toto movemove offoff thethe unit:unit:

USUS ofof thethe extremitiesextremities andand TEETEE (( espesp inin thethe MVMV pt.)pt.)

AcuteAcute PulmonaryPulmonary EmbolismEmbolism inin thethe CriticalCritical CareCare Unit:Unit: IsIs itit differentdifferent ??

CaseCase PresentationPresentation TheThe RiskRisk FactorFactor andand IncidenceIncidence ofof VTEVTE inin MICUMICU patientspatients DiagnosisDiagnosis ofof VTEVTE inin MICUMICU PatientsPatients ImpactImpact ofof currentcurrent prophylaxisprophylaxis onon thethe preventionprevention ofof DVTDVT inin MICUMICU patientspatients

ACCPACCP RecommendationsRecommendations 20042004 CriticalCritical CareCare UnitUnit

UponUpon admissionadmission toto aa criticalcritical carecare unitunit,, allall patientspatients shouldshould bebe assessedassessed forfor theirtheir riskrisk ofof DVT/PEDVT/PE

Accordingly,Accordingly, mostmost shouldshould receivereceive thromboprophylaxisthromboprophylaxis (grade(grade 1A)1A) LowLow--molecularmolecular--weightweight heparinheparin (LMWH)(LMWH) LowLow--dosedose unfractionatedunfractionated heparinheparin (UFH)(UFH) (q(q 1212 hh oror qq 88 h)h)

ACCP=American College of Chest Physicians

Geerts WH et al. Chest. 2004;126(3 suppl):338S-400S.

1212 hh oror qq 88 h)h) ACCP=American College of Chest Physicians Geerts WH et al. Chest

InitialInitial ProphylaxisProphylaxis ConsiderationsConsiderations inin CriticalCritical CareCare PatientsPatients

HighHigh bleedingbleeding riskrisk MechanicalMechanical prophylaxisprophylaxis DelayDelay prophylaxisprophylaxis untiluntil highhigh bleedingbleeding riskrisk resolvesresolves ScreenScreen forfor proximalproximal DVTDVT withwith DUSDUS inin highhigh riskrisk patientspatients

UsualUsual bleedingbleeding riskrisk LowLow--dosedose UFHUFH 5,0005,000 UU qq 88 hh LMWHLMWH CombineCombine ACAC andand mechanicalmechanical prophylaxisprophylaxis

GeertsGeerts W,W, etet al.al. JJ CritCrit CareCare 2002;2002;1:951:95--104104

TrialsTrials forfor VTEVTE prophylaxisprophylaxis inin thethe ICUICU

Study/YearStudy/Year

Size,Size, nn

TypeType ofof ICUICU PatientPatient

MethodMethod ofof

ControlControl

ActiveActive TxTx

ResultsResults

DetectionDetection

CadeCade

119119

GeneralGeneral

FUTFUT forfor 14d14d

PlaceboPlacebo

UFHUFH 50005000

2929

v.v. 13%13%

19821982

ICUICU

bidbid

 

KapoorKapoor

791791

MedicalMedical

DUSDUS onon qq 33 daysdays

PlaceboPlacebo

UFHUFH 50005000

3131

v.v. 11%11%

1999abst1999abst

ICUICU

bidbid

 

FraisseFraisse

223223

VentilatedVentilated

VenographVenograph byby dayday 2121

PlaceboPlacebo

NadroparinNadroparin 6565 U/kgU/kg SCSC qq dayday

2828

v.v. 15%15%

20002000

COPDCOPD

 

GoldhaberGoldhaber

325325

MedicalMedical

DUSDUS onon

UFHUFH 50005000

Enoxapar.Enoxapar. 300300 mgmg bidbid

1313

v.v. 16%16%

2000abst2000abst

ICUICU

dayday 3,7,103,7,10

bidbid

 

CookCook

129129

MedMed--SurgSurg

CUSCUS

UFHUFH 50005000

DalteparinDalteparin

NRNR vv NRNR

ICUICU

bidbid

50005000 IU/dIU/d

DoDo mechanicalmechanical prophylaxisprophylaxis devicesdevices reducereduce DVTDVT incidenceincidence inin ICUICU patients?patients?

StimulatesStimulates endogenousendogenous fibrinolysisfibrinolysis productionproduction ofof plasminogenplasminogen activatoractivator MoreMore efficaciousefficacious inin moderatemoderate riskrisk postpost-- operativeoperative patientspatients RobustRobust datadata lackinglacking efficacyefficacy inin medicalmedical ICUICU patientspatients

INTERMITTENT PNEUMATIC COMPRESSION

INTERMITTENT PNEUMATIC COMPRESSION Indication: contraindication to anticoagulation Evidence: limited Compliance: poor

Indication: contraindication to anticoagulation

Evidence: limited

Compliance: poor

Cost:

$56.00 per day equipment rental

Bleeding risk: NONE

CombinationCombination StrategyStrategy

RandomizedRandomized trialtrial ofof 2,5512,551 consecutiveconsecutive cardiaccardiac surgicalsurgical patients.patients. SCDsSCDs ++ LDUHLDUH –– 62%62% reductionreduction inin postpost--surgicalsurgical PEPE (( 1.5%1.5% vsvs 4%)4%) ** NonhemorrhagicNonhemorrhagic StrokeStroke –– 4040 foldfold reductionreduction riskrisk ofof DVT**DVT**

*Ramos R. et.al. Chest 1996 **Kamran SL. Et.al. Neurology 1998

RoleRole ofof MechanicalMechanical prophylaxisprophylaxis inin preventingpreventing DVTDVT inin highhigh riskrisk populations:populations: StannardStannard JP.JP. JJ BoneBone andand JointJoint SurgerySurgery 2006:2006: 88;88; 261261 --266266

224224 patientspatients withwith bluntblunt traumatrauma –– prospectiveprospective studystudy investigatinginvestigating VTEVTE GroupGroup AA (97)(97) –– enoxaparinenoxaparin SQSQ BIDBID startingstarting 2424 –– 4848 hrshrs afterafter bluntblunt traumatrauma GroupGroup BB (103)(103) –– pulsatilepulsatile footfoot pumpspumps atat timetime ofof admissionadmission andand delayeddelayed enoxaparinenoxaparin GroupGroup AA –– 1313 DVTsDVTs (13.4%)(13.4%) andand 22 PEsPEs (2.1%)(2.1%) GroupGroup BB –– 99 DVTsDVTs (( 8.7%)8.7%) nono PEsPEs GroupGroup AA –– 1111 largelarge andand occulsiveocculsive clotsclots (11.3%)(11.3%) GroupGroup BB –– 33 largelarge andand occlussiveocclussive clotsclots (2.9%)(2.9%)

p=0.025p=0.025

PreventionPrevention ofof VTEVTE inin thethe ObeseObese MICUMICU PatientPatient

AntiAnti--XaXa levelslevels withwith fixedfixed dosedose LMWHLMWH regimensregimens correlatecorrelate negativelynegatively withwith BMIBMI inin criticacriticallylly illill patientspatients (Priglinger(Priglinger UU

2003)2003)

StandardStandard prophylacticprophylactic regimensregimens areare twicetwice asas likelylikely toto failfail inin

BIDBID –– ScholScholtenten DJ.DJ. 20022002

orthopedicorthopedic patientspatients withwith BMIBMI >32>32 BMIBMI >> 3232 VTEVTE raterate 32%32% vsvs 17%17% BMIBMI <32<32 ––SamamaSamama MM,MM, 19951995 NonrandomizedNonrandomized studiesstudies inin bariatbariatricric surgerysurgery patientspatients suggestsuggest

aa decreasedecrease DVTDVT ratesrates withwith enoxaparinenoxaparin 40mg40mg sqsq BIDBID vsvs 30mg30mg

NoNo datadata toto guideguide adjustmentsadjustments inin therapytherapy

OptionsOptions include:include:

UseUse standardstandard dosedose

EmpiricEmpiric dosedose adjustmentsadjustments

AddAdd mechanicalmechanical measuresmeasures

MICUMICU PatientPatient withwith RenalRenal Insufficiency:Insufficiency:

VTEVTE PreventionPrevention

DelayedDelayed renalrenal clearanceclearance ofof LMWHsLMWHs andand FondaparinuxFondaparinux veryvery problematicproblematic LackLack ofof outcomesoutcomes basedbased datadata FDAFDA approvedapproved enoxaparinenoxaparin 3030 mgmg sqsq qdqd forfor patientspatients withwith CCLCCL <30<30 ml/minml/min basedbased onon pharmacokineticpharmacokinetic datadata alonealone AdditionalAdditional optionsoptions UFUUFU and/orand/or mechanicalmechanical devices.devices.

ElderlyElderly PatientPatient inin thethe MICUMICU

MaheMahe et.al.et.al. monitoredmonitored antianti--XaXa levelslevels inin 6868 consecutiveconsecutive hospitalizedhospitalized elderlyelderly patientspatients (mean(mean ageage 82)82) receivingreceiving enoxaparinenoxaparin 40mg40mg sqsq qdqd forfor prophylaxisprophylaxis DayDay 22 >50%>50% hadhad levelslevels >0.5IU/ml>0.5IU/ml (( optimaloptimal range)range) DayDay 88 69.469.4 levelslevels >0.5>0.5 IU/mlIU/ml BEBE CAREFUL:CAREFUL: considerconsider empiricempiric reductionreduction ofof enoxaparinenoxaparin oror useuse mechanicalmechanical devicesdevices alonealone inin elderlyelderly withwith lowlow bodybody weightweight << 4545 kgkg oror marginalmarginal creatininecreatinine clearaneclearane

PatientsPatients withwith PriorPrior HITHIT

TreatmentTreatment ofof HITHIT isis aa thrombinthrombin inhibitorinhibitor bridgebridge toto warfarinwarfarin therapytherapy OptimalOptimal futurefuture VTEVTE preventionprevention strategiesstrategies areare lackinglacking inin thisthis populationpopulation

AvoidAvoid UFHUFH andand LMWHLMWH DTIsDTIs areare impracticalimpractical forfor primaryprimary VTEVTE prophylaxisprophylaxis FondaparinuxFondaparinux –– indirectindirect antianti--XaXa inhibitorinhibitor maymay bebe aa promisingpromising prophylaxisprophylaxis schemescheme

FondaparinuxFondaparinux doesdoes notnot bindbind plateletplatelet factorfactor 44 NoNo apparentapparent inin vitrovitro crosscross reactivityreactivity toto HITHIT antibiodiesantibiodies

ProphylacticProphylactic AnticoagulationAnticoagulation WithWith Enoxaparin:Enoxaparin: IsIs thethe SubcutaneousSubcutaneous RouteRoute AppropriateAppropriate inin thethe CriticallyCritically Ill?Ill?

PriglingerPriglinger U,U, DelleDelle KarthKarth G,G, GeppertGeppert A,A, JoukhadarJoukhadar C,C, GrafGraf S,S, BerBergerger R,R, HHüülsmannlsmann M,M, SpitzauerSpitzauer S,S, PabingerPabinger I,I, HeinzHeinz GG

CriticalCritical CareCare MedicineMedicine 2003.2003. 31:140531:1405--409409

Objective:Objective: DetermineDetermine antianti--XaXa activitiesactivities inin criticallycritically illill patientspatients andand inin noncriticallynoncritically illill patientspatients receivingreceiving prophylacticprophylactic dosesdoses ofof subcutaneoussubcutaneous enoxaparinenoxaparin

ProphylacticProphylactic AnticoagulationAnticoagulation WithWith Enoxaparin:Enoxaparin:

IsIs thethe SCSC RouteRoute AppropriateAppropriate inin thethe CriticallyCritically Ill?Ill?

1.01.0 FF overover timetime == 39,39, PP == 0.0010.001 ICUICU patientspatients (n(n == 16)16) GeneralGeneral
1.01.0
FF overover timetime == 39,39, PP == 0.0010.001
ICUICU patientspatients (n(n == 16)16)
GeneralGeneral wardward (n(n == 13)13)
FF betweenbetween groupsgroups == 23,23, PP == 0.0010.001
0.80.8
0.60.6
0.40.4
0.20.2
00
00
33
66
99
1212
(U/mL)Anti-Xa
Anti-Xa activity
activity (U/mL)

TimeTime (hours)(hours)

ProphylacticProphylactic AnticoagulationAnticoagulation WithWith Enoxaparin:Enoxaparin:

IsIs thethe SCSC RouteRoute AppropriateAppropriate inin thethe CriticallyCritically Ill?Ill?

1.01.0 FF overover timetime == 43.2,43.2, PP == 0.0010.001 ICUICU patientspatients (n(n == 16)16) GeneralGeneral
1.01.0
FF overover timetime == 43.2,43.2, PP == 0.0010.001
ICUICU patientspatients (n(n == 16)16)
GeneralGeneral wardward (n(n == 13)13)
FF betweenbetween groupsgroups == 1.5,1.5, PP == 0.20.2
0.80.8
0.60.6
0.40.4
0.20.2
00
00
2424
4848
7272
9696
120120
(U/mL)Anti-Xa
Anti-Xa activity
activity (U/mL)

TimeTime (hours)(hours)

ProphylacticProphylactic AnticoagulationAnticoagulation WithWith Enoxaparin:Enoxaparin:

IsIs thethe SCSC RouteRoute AppropriateAppropriate inin thethe CriticallyCritically Ill?Ill?

Conclusion:Conclusion: CriticallyCritically illill patientspatients withwith normalnormal renalrenal functionfunction demonstrateddemonstrated significantlysignificantly lowerlower antianti--XaXa levelslevels inin responseresponse toto aa singlesingle dailydaily dosedose ofof subcutaneoussubcutaneous enoxaparinenoxaparin whenwhen comparedcompared withwith medicalmedical patientspatients inin thethe normalnormal ward.ward.

THETHE EVALUATIONEVALUATION OFOF VENOUSVENOUS THROMBOETHROMBOEMBOLISMMBOLISM PROPHYLAXISPROPHYLAXIS THERAPYTHERAPY ININ AA

MEDICALMEDICAL INTENSIVEINTENSIVE CARECARE UNITUNIT VIAVIA THERAPEUTICTHERAPEUTIC DRUGDRUG MONITORINGMONITORING

H.H. Patel,Patel,

A.A. Velasquez,Velasquez, D.D. Shaz,Shaz, K.K. Leeper,Leeper, Pulmonary/CriticalPulmonary/Critical CareCare MediciMedicine,ne, EmoryEmory Healthcare,Healthcare, Atlanta,Atlanta, GA;GA;

IntroductionIntroduction :: PatientsPatients inin aa medimedicalcal intensiveintensive carecare unitunit (MICU)(MICU) areare oftenoften atat veryvery highhigh riskrisk ofof developingdeveloping aa venousvenous thromboembolismthromboembolism (VTE).(VTE). HepHeparinarin andand lowlow molecularmolecular weightweight heparinsheparins (LMWHs)(LMWHs) areare pharmacologicalpharmacological agagentsents usedused forfor preventionprevention ofof VTE.VTE.

Hypothesis:Hypothesis: CurrentCurrent dosingdosing guidelinesguidelines forfor VTEVTE prophylaxisprophylaxis maymay bebe inadequateinadequate inin MICUMICU patientspatients whowho oftenoften havehave alteredaltered pharmacokinetpharmacokineticic andand pharmacodynamicpharmacodynamic profiles.profiles.

MethodsMethods :: PatientsPatients inin thethe MICUMICU receivingreceiving VTEVTE prophylaxisprophylaxis withwith heheparinparin oror LMWHLMWH hadhad antianti--XaXa levelslevels monitoredmonitored inin thisthis prospective,prospective, observationalobservational study.study. AntiAnti--XaXa levelslevels werewere drawndrawn atat leastleast afterafter 44 dosesdoses andand 44 hourshours afterafter subcutaneoussubcutaneous administrationadministration ofof medication.medication.

THETHE EVALUATIONEVALUATION OFOF VENOUSVENOUS THROMBOETHROMBOEMBOLISMMBOLISM PROPHYLAXISPROPHYLAXIS THERAPYTHERAPY ININ

AA MEDICALMEDICAL INTENSIVEINTENSIVE CARECARE UNITUNIT VIAVIA THERAPEUTICTHERAPEUTIC DRUGDRUG MONITORINGMONITORING

H.H.

Patel,Patel, A.A. Velasquez,Velasquez, D.D. Shaz,Shaz, K.K. LeepLeeper,er, Pulmonary/CriticalPulmonary/Critical CareCare MediMedicine,cine, EmoryEmory Healthcare,Healthcare, Atlanta,Atlanta, GA;GA;

ResultsResults :: FromFrom MarchMarch 20072007 toto AugustAugust 2007,2007, 5050 patientspatients hadhad antianti--XaXa levelslevels monitored.monitored. AmongAmong thethe 5050 patients,patients, 1212 patientspatients (24%)(24%) acheivedacheived appropriateappropriate antianti--XaXa levelslevels comparedcompared toto 3838 patientspatients (76%)(76%) whowho werewere nonnon-- therapeutic.therapeutic. AmongAmong thosethose inin thethe apappropriatepropriate range,range, 88 patientspatients (6(67%)7%) werewere receivingreceiving LMWH.LMWH. ICUICU lengthlength ofof staystay andand daysdays onon thethe ventilatorventilator wewerere longerlonger inin patientspatients withwith nonnon--therapeutictherapeutic antianti--XaXa levels.levels.

ConclusionsConclusions :: CurrentCurrent dosingdosing guidelinesguidelines ofof heparinheparin forfor VTEVTE prophprophylaxisylaxis areare inadequateinadequate inin anan MICUMICU setting.setting. WeightWeight basedbased dosingdosing ofof hepariheparinn shouldshould bebe consideredconsidered inin futurefuture patients.patients. TheThe LMWHsLMWHs maymay havehave aa bebettertter predictability.predictability. FutureFuture studiesstudies shouldshould evaluateevaluate whetherwhether subtherapsubtherapeuticeutic VTEVTE prophylaxisprophylaxis correlatescorrelates toto aa hihighergher incidenceincidence ofof VTEVTE comparedcompared toto therapeutictherapeutic dosing.dosing.

StrategiesStrategies toto ImproveImprove ThromboprophylaxisThromboprophylaxis

ComparisonComparison ofof strategiesstrategies amongamong 1,8271,827 patientspatients inin 33 similarsimilar CCUsCCUs

NoNo specialspecial compliancecompliance interventionintervention

EducationEducation providedprovided toto physiciansphysicians

EducationEducation andand mandatorymandatory computercomputer orderorder entryentry

38%38%

62%62%

97%97%

SummarySummary

CriticallyCritically illill patientspatients areare atat highhigh riskrisk ofof VTEVTE

LowLow raterate ofof clinicalclinical diagnosisdiagnosis

PrevalencePrevalence 1010 –– 60%60%

PredominantPredominant test:test: ultrasoundultrasound

ProphylaxisProphylaxis

UFHUFH 50005000 UU qq 88 hh LMWHLMWH (enoxaparin(enoxaparin 4040 mgmg SC/d)SC/d)

DalteparinDalteparin 50005000 IUIU SCSC dailydaily

FondaparinuxFondaparinux 2.52.5 mgmg SQSQ dailydaily

IntermittentIntermittent compressioncompression devicesdevices

UtilizationUtilization ofof prophylaxisprophylaxis isis ininadequateadequate ANDAND oror prophylacticprophylactic

regimensregimens maymay bebe inadequateinadequate NewNew sourcessources ofof thrombithrombi –– HITHIT inducedinduced thrombosisthrombosis

WeWe cancan dodo betterbetter !!!!!!

TreatmentTreatment ofof VTEVTE inin thethe CriticalCritical CareCare PatientsPatients

KennethKenneth V.V. LeeperLeeper Jr.Jr. MDMD AssociateAssociate ProfessorProfessor ofof MedicineMedicine DivisionDivision ofof Pulmonary,Pulmonary, AllergAllergyy andand CriticalCritical CareCare MedicineMedicine EmoryEmory SchoolSchool ofof MedicineMedicine Atlanta,Atlanta, GeorgiaGeorgia

SummarySummary ofof SixthSixth AmericanAmerican CollegeCollege ofof ChestChest PhysiciansPhysicians (ACCP)(ACCP) GuidelinesGuidelines forfor AntithrombotAntithromboticic TherapyTherapy inin thethe TreatmentTreatment ofof VenousVenous ThromboembolismThromboembolism

Recommendations

Guidelines for Treatment

Grade 1A

i.v. LMWH/UFH or adjusted-dose s.c. heparin initially for at least 5 days Overlap with oral anticoagulation for at least 4-5 days Discontinue LMWH/UFH on day 5/6 if INR is therapeutic for 2 consecutive days

Grade 2B

LMWH preferred over UFH

Grade 1C

Massive pulmonary embolism/severe iliofemoral thrombosis: LMWH/UFH for approximately 10 days

Grade 1C+

LMWH: dose based on manufacturers’ instructions UFH: adjust to correspond to a plasma heparin level of 0.2-0.4 IU/mL (protamine sulfate) or 0.3-0.4 IU/mL (amidolytic anti-Xa assay)

5656 y.oy.o manman withwith aa historyhistory ofof alcalcoholismoholism admittedadmitted toto thethe MICUMICU inin respiratoryrespiratory failurefailure secondarysecondary toto pneumonia.pneumonia. HeHe isis onon nono vasopressorsvasopressors andand renalrenal functionfunction isis normalnormal andand onon heparinheparin 50005000 ununitsits sqsq BIDBID

OnOn dayday 55 hishis WBCWBC countcount isis normalnormal butbut temperaturetemperature isis 38.6C38.6C DifferentialDifferential Dx:Dx: 1.Slow1.Slow resolutionresolution ofof thethe pneumonia.pneumonia. 2.2. VAP.VAP. 33 PossiblePossible DVTDVT Evaulation:Evaulation: MiniMini BALBAL negative,negative, LELE dopplersdopplers PositivePositive forfor DVTDVT rightright deepdeep femoralfemoral Treatment:Treatment: NoNo contraindicationscontraindications toto heparinheparin therapy:therapy: TreatTreat withwith UFUUFU oror LMWHLMWH

TherapeuticTherapeutic peakpeak antianti--XaXa levelslevels withwith LMWHsLMWHs forfor thethe treatmenttreatment ofof VTEVTE

EnoxaparinEnoxaparin 1mg/kg1mg/kg qq 1212 hrshrs EnoxaparinEnoxaparin 1.5mg/kg1.5mg/kg qdqd TinzaparinTinzaparin 175175 IU/kgIU/kg qdqd DalteparinDalteparin 100IU/kg100IU/kg qq 1212 hrshrs DalteparinDalteparin 200200 IU/kgIU/kg qdqd ProphylaxisProphylaxis

0.60.6--1.0IU/ml1.0IU/ml

1.01.0 ––1.51.5 IU/mlIU/ml 0.850.85 –– 1.01.0 IU/mlIU/ml 0.40.4 –– 1.11.1 IU/mlIU/ml 1.01.0--2.02.0 IU/mlIU/ml 0.10.1 0.60.6 IU/mlIU/ml

Chromogenic anti-Xa level assay drawn 4 hours after the subq dose

ThisThis isis aa 6262 y.oy.o womanwoman withwith diabdiabetesetes andand ESRD,ESRD, admittedadmitted toto thethe MICUMICU withwith MRSAMRSA bacteriemia.bacteriemia. TheThe patientpatient isis placedplaced onon SCDsSCDs forfor DVDVTT prophylaxis.prophylaxis. OnOn MICUMICU dayday 44 shshee developesdevelopes aa suddensudden onsetonset ofof dyspneadyspnea ,hypoxemia,hypoxemia andand SPBSPB ofof 9898 mmHgmmHg

Evaluation:Evaluation: SpiralSpiral CTCT scanscan ofof thethe chestchest –– largelarge rightright mainmain pulmonarypulmonary embolism.embolism. LELE dopplersdopplers –– RightRight poplitealpopliteal DVT.DVT. TEETEE –– ModerateModerate RVRV dilationdilation withwith parodoxicalparodoxical septalseptal shift.shift. ManagementManagement

HypotensionHypotension respondedresponded toto fluidfluid therapytherapy PharmacologicPharmacologic managementmanagement andand otherother optionsoptions

UFHUFH infusioninfusion UFHUFH infusioninfusion andand retrieveableretrieveable filterfilter ThrombolysisThrombolysis PulmonaryPulmonary embolectomyembolectomy

andand retrieveableretrieveable filterfilter ThrombolysisThrombolysis PulmonaryPulmonary embolectomyembolectomy

5151 y.oy.o manman underwentunderwent coronarycoronary arteryartery bypassbypass surgerysurgery complicatedcomplicated byby aa hemopericardium,hemopericardium, requiringrequiring pericardialpericardial windowwindow drainage.drainage.

FifthFifth postpost –– opop dayday prophylacticprophylactic therapytherapy withwith enoxaparinenoxaparin waswas started.started. 99 thth postpost--opop dayday feverfever toto 39C39C andand hypotensionhypotension withwith BPBP 90/70,90/70, abdominalabdominal tendernesstenderness andand distention.distention. AdmissionAdmission plateletplatelet countcount –– 182X109182X109 cells/lcells/l postpost--opop dayday 3,3, nownow –– 4040 X109X109 cellscells cells/lcells/l

5151 y.oy.o manman underwentunderwent coronarycoronary arteryartery bypassbypass surgerysurgery complicatedcomplicated byby aa hemopericardium,hemopericardium, requiringrequiring pericardialpericardial windowwindow drainagedrainage

DifferentialDifferential Diagnosis:Diagnosis: SepsisSepsis withwith DICDIC ManagementManagement

DifferentialDifferential Diagnosis:Diagnosis: SepsisSepsis withwith DICDIC ManagementManagement

MovedMoved toto thethe ICUICU

AntibioticsAntibiotics andand fluidsfluids startedstarted

DICDIC profileprofile negativenegative

SerumSerum cortisolcortisol orderedordered

ArgatrobanArgatroban startedstarted

HITHIT –– ELISAELISA forfor heparinheparin –– inducedinduced PFPF 44 antibodiesantibodies stronglystrongly positivepositive

CTscanCTscan ofof abdomenabdomen –– revealedrevealed bilateralbilateral adrenaladrenal necrosisnecrosis

SerumSerum cortisolcortisol << 1ug/ml1ug/ml

PatientPatient improvedimproved –– dischargeddischarged onon adrenaladrenal replacementreplacement andand warfarinwarfarin

5151 y.oy.o manman underwentunderwent coronarycoronary arteryartery bypassbypass surgerysurgery complicatedcomplicated byby aa hemopericardium,hemopericardium, requiringrequiring pericardialpericardial windowwindow drainage:drainage: CommentComment

IfIf therethere isis aa moderatemoderate suspicionsuspicion ofof HITHIT -- treattreat withwith DTIDTI LargeLarge amountamount ofof heparinheparin duringduring bypassbypass waswas sensitizingsensitizing alongalong withwith thethe LMWH.LMWH. WhenWhen heparinheparin waswas stoppedstopped greatestgreatest riskrisk periodperiod forfor newnew thromboembolicthromboembolic complicationscomplications AdrenalAdrenal necrosisnecrosis isis aa microthromboticmicrothrombotic lesionlesion withwith secondarysecondary necrosisnecrosis andand hemorrhagehemorrhage Diagnosis:Diagnosis: HITHIT withwith acuteacute adrenaladrenal crisiscrisis

IncidenceIncidence ofof HITHIT andand VTEVTE AfterAfter UseUse ofof UFHUFH andand LMWHLMWH

LiteratureLiterature review:review: IdentifyIdentify ststudiesudies usingusing UFHUFH oror LMWHLMWH forfor thromboprophylaxisthromboprophylaxis oror treatmentreatmentt inin whichwhich newnew oror recurrentrecurrent VTEVTE andand serologicallyserologically confirmedconfirmed HITHIT 1010 studiesstudies

386386 ofof 6,2196,219 heparinheparin--treatedtreated patientspatients hadhad VTEVTE 3232 ofof 386386 VTEVTE patientspatients alsoalso hadhad HITHIT

AmongAmong 3232 casescases ofof HITHIT inin 386386 VTEVTE patientspatients

1717 casescases occurredoccurred inin 129129 IVIV UFHUFH--treatedtreated patientspatients (13.2%)(13.2%)

1414 casescases occurredoccurred inin 113113 SCSC UFHUFH--treatedtreated patientspatients (12.4%)(12.4%)

11 casecase occurredoccurred inin 144144 LMWHLMWH--treatedtreated patientspatients (0.7%)(0.7%)

LevineLevine RL,RL, etet al.al. ChestChest 2006;130:6812006;130:681--7.7.

PretestPretest ScoringScoring SystemSystem forfor HIT.HIT. WarkenteninWarkentenin andand Heddle.Heddle. CurrCurr HematolHematol RepRep 20032003

4Ts

2 Points

1 point

0 points

Thrombocytopenia

Platelet count >50% and platelet nadir >20 X109/L

Platelet count> 30-

Platelet count < 30%

50%

Timing of platelet count decrease

Clear onset between days 5 -10 or platelet dec with one day

Consistent with immunization but unclear history

Platelet count <4 days without recent exposure

Thrombosis or other sequelae

New thrombosis, skin necrosis, systemic rx to post IV UFU bolus

Suspected thrombosis not yet proven

None

Other causes of thrombocytopenia

No apparent

Possible

Definite