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Preventionofvenousthromboembolicdiseaseinsurgicalpatients
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Preventionofvenousthromboembolicdiseaseinsurgicalpatients
Authors
MenakaPai,MD,FRCPC
JamesDDouketis,MD,FRCPC,
FACP,FCCP

SectionEditors
LawrenceLKLeung,MD
JessMandel,MD

DeputyEditor
GeraldineFinlay,MD

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Jun2016.|Thistopiclastupdated:Apr22,2016.
INTRODUCTIONUsingthe2003nationwideinpatientsamplefromtheHealthCareCostandUtilizationProjectin
theUnitedStates,therewereover38milliondischargesin2003[1].Twentypercentofthoseweresurgicalinpatients
and,usingtheACCPGuidelinesforriskstratification,itwasestimatedthat15percent,24percent,and17percent
wereatmoderate,high,orveryhighriskforvenousthromboembolism(VTE,whichincludesdeepveinthrombosisand
pulmonaryembolism).
DespitesignificantadvancesinthepreventionandtreatmentofVTE,pulmonaryembolismremainsthemostcommon
preventablecauseofhospitaldeath[26],responsibleforapproximately150,000to200,000deathsperyearinthe
UnitedStates[7,8].Thus,itisvitalthateffortscontinuetobemadetofindthesafestandmosteffectivemeansof
preventingandmanagingVTE.
PracticalapproachestothepreventionofVTEinsurgicalpatientswillbereviewedhere.PreventionofVTEinmedical
patientsispresentedseparately.(See"Preventionofvenousthromboembolicdiseaseinacutelyillhospitalizedmedical
adults".)
DetaileddiscussionsaboutspecificpharmacologicagentsemployedforVTEpreventionarepresentedseparately.(See
"HeparinandLMWheparin:Dosingandadverseeffects"and"WarfarinandotherVKAs:Dosingandadverseeffects"
and"Fondaparinux:Dosingandadverseeffects"and"Lowmolecularweightheparinforvenousthromboembolic
disease".)
PROBLEMOVERVIEWIntheUnitedStatestherehavebeenanumberofinitiativesaimedatcallingattentionto
theprevalenceofVTEandincreasingtheuseofprophylaxisofVTEinthehospitalsetting.Theseinitiativeshave
comefromtheNationalQualityForum[9],theSurgicalCareImprovementProject[10],theCentersforMedicineand
MedicinalServices,theJointCommissiononAccreditationofHealthCareOrganizations[11],andtheOfficeofthe
SurgeonGeneraloftheUnitedStates[12].SimilarinitiativeshavebeendevelopedinCanada[13],theUnitedKingdom
[14,15],andEurope.
AccordingtotheAgencyforHealthcareResearchandQuality,thepreventionofVTEisthenumberonestrategyto
improvepatientsafetyinhospitals[16].Asanexample,aspartoftheSurgicalCareImprovementProject,theCenter
forMedicareandMedicaidServices(CMS)nowconsidersappropriateVTEprophylaxistobeapayforperformance
qualitymeasureforspecificprocedures(table1)[1719].Effectiveandsafeprophylacticmeasuresarenowavailable
formosthighriskpatients[2023],andnumerousevidencebasedguidelineshavebeenpublishedforthepreventionof
VTE[2426].
Inspiteoftheavailabilityoftheseguidelinesandtheavailabilityofsafeandeffectiveprophylacticagents,numerous
auditshavedemonstratedthatappropriatethromboprophylaxisisnotbeingofferedtolargenumbersofsurgicalpatients
[2733].Asexamples:
TheENDORSEstudyevaluatedVTEriskandprophylaxisinallhospitalinpatients18yearsofageadmittedto
asurgicalwardin358hospitalsfrom32differentcountries[28,34].Forthe30,827surgicalpatientsinthisstudy,
64.4percent(rangebetweencountries:44to80percent)werejudgedtobeatriskforVTEaccordingtothe
AmericanCollegeofChestPhysicians(ACCP)Guidelinesavailableatthattime.However,only58.5percent
(rangebetweencountries:0.2to92percent)oftheatrisksurgicalpatientsreceivedACCPrecommendedVTE
prophylaxis.
InaCanadianstudyof10,744patients65yearsofagewhohadhiporkneereplacementtherapy,only19
percentreceivedthromboprophylaxisatthetimeofhospitaldischarge[30].Ofimportance,theriskofshortterm
mortality(ie,deathwithinthreemonthsofdischarge)wassignificantlyloweramongthosewhoreceivedpost
dischargethromboprophylaxis(hazardratio0.3495%CI0.200.57).
Variousstrategiestoimprovetheuseofthromboprophylaxishavebeendemonstratedtobeeffective,including
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computerizedordersetswithelectronicalerts,orpreprintedordersandqualityimprovementintheformofclinician
educationprograms,audit,andfeedback,butfurthereffortsarerequiredatimprovingthetranslationofdatafrom
clinicaltrialsintoclinicalpractice[3542].
RISKFACTORSFORVTETherearenumerousriskfactorsforthedevelopmentofVTEinsurgicalpatients,
includingthetypeandextentofsurgeryortrauma,durationofhospitalstay,ahistoryofpreviousVTEorcancer,
immobility,recentsepsis,presenceofacentralvenousaccessdevice,pregnancyorthepostpartumperiod,and
inheritedoracquiredhypercoagulablestates[4360].Forsurgicalpatients,prophylaxishasbeenrecommended
accordingtoassignmentofthepatienttooneofthedefinedsurgicalriskgroupsdescribedbelow[25].
IncidenceIntheabsenceofappropriateprophylaxis,theincidenceofasymptomaticDVTdetectedbyobjective
diagnosticscreeningtestshasrangedfrom10to80percentinvarioushospitalizedmedicalandsurgicalgroups[24].
Fromearlierstudies,theincidenceoffatalpulmonaryembolismintheabsenceofprophylaxiswasestimatedtobe0.1
to0.8percentinpatientsundergoingelectivegeneralsurgery,2to3percentinpatientshavingelectivetotalhip
replacement,and4to7percentofpatientsundergoingsurgeryforafracturedhip[24].
Theseestimatesarelikelylowertodaybecauseoftheincreasinguseofearlyambulationandshorterlengthsof
hospitalization.However,datafromauditsandregistriesdemonstratethattheincidenceofVTE,andinparticularfatal
pulmonaryembolism,remainsexcessivelyhigh,evenafterhospitaldischarge.
Asanexample,inaprospectivecohortstudyof947,454middleagedwomenintheUK,anestimated1in140women
undergoinginpatientsurgeryintheUKwillbeadmittedwithvenousthromboembolismduringthe12weekperiod
followingsurgery,1in815afteroutpatientsurgery,andonly1in6200womennotundergoingsurgery[61].No
informationwasavailableontheuseornonuseofVTEprophylaxisinthiscohortofpatients.
SurgicalriskgroupsTheriskofpostoperativeVTEdependsuponanumberoffactorsrelatedtothesurgical
procedureitself(eg,degreeofinvasiveness,typeanddurationofanaesthesia,requirementforimmobilization)[62,63],
aswellasanumberofpatientrelatedadverseriskfactors[15,24,25,6466].(See"Overviewofthecausesofvenous
thrombosis",sectionon'Acquiredriskfactors'.)

Increasingage
PriorVTEinpatientorfamilymembers
Presenceofmalignancyorobesity
Presenceofaninheritedoracquiredhypercoagulablestate
Oneormoresignificantmedicalcomorbidities(eg,heartdisease,infection,inflammatoryconditions,recent
stroke,preoperativesepsis)

Inaddition,certainprocedurescanbeshowntoincreasethrombingeneration,furtherincreasingthromboticrisk(eg,
reamingoutofthefemurduringtotalhipreplacementsurgery)[67].
The2012ACCPGuidelineshavedividedpatientsundergoingsurgicalproceduresintoverylow,low,moderate,orhigh
riskgroups[68].Althoughtherehavebeenmanyattemptstoquantitatetheserisks,noonemethodhasbeenfoundto
beuniversallyacceptable.Thus,thecaveatisthatifapatienthasadditionalriskfactors,considerationshouldbegiven
toeitherincreasingtheintensityorthedurationoftheprophylacticagent[25,38].
Themostwidelytestedsurgicalriskassessmentmodel(theModifiedCapriniRiskAssessmentModel,Capriniscore)
hasbeenslightlymodifiedforuseinthe2012ACCPGuidelinesandisdescribedintheaccompanyingtable(table2)
[64,6870].Thisriskmodelwillbeusedthroughoutthisreviewtodeterminethesurgicalriskgroupslistedbelow.
VerylowriskpatientsVerylowriskpatientshavebeendefinedasthoseundergoinggeneralandabdominal
pelvicsurgerywithaCapriniscoreofzero,andthoseundergoingplasticandreconstructivesurgerywithaCaprini
scoreofzerototwo.TheirestimatedbaselineriskofVTEintheabsenceofprophylaxisisestimatedtobelessthan
0.5percent.
AprospectiveobservationalcohortstudyusingtheAmericanCollegeofSurgeonsNationalSurgicalQuality
ImprovementProgramwasusedtoidentifyindependentpredictorsof30dayVTEeventsrequiringtreatmentfollowing
outpatientorsamedaysurgery[71].The30dayincidenceofVTEforthe173,501subjectsinthederivationcohortwas
0.15percent,andwas0.06and1.18percentamongthoseinthelowestandhighestriskcategories,respectively.
ResultsofthisstudymustbeinterpretedincontextitwasunabletoprovidedetailsontheuseofVTEprophylaxisor
commonVTEriskfactors,suchaspersonalorfamilyhistoryofVTE.Nineindependentriskfactorswereidentified,
includingage40to59years,age60years,currentpregnancy,activecancer,increasedbodymassindex,operative
time120minutes,arthroscopicsurgery,saphenofemoraljunctionsurgery,andvenoussurgerynotinvolvingthegreat
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saphenousvein.Eventhehighestriskpatientsusingthisoutpatientmodelfitinthelowrisksurgicalgroup,despite
thefactthatsomeoftheidentifiedriskfactorsmayplaceagivenpatientinthehighestCapriniriskgroup.
LowriskpatientsLowrisksurgicalpatientshavebeendefinedasthoseundergoinggeneralandabdominal
pelvicsurgerywithaCapriniscoreof1to2,orthoseundergoingplasticandreconstructivesurgerywithaCaprini
scoreof3to4.TheirestimatedbaselineriskofVTEintheabsenceofprophylaxisisestimatedtobeapproximately
1.5percent.
Inmostcases,lowrisksurgicalpatientsarethoseundergoingminorelectiveabdominalorthoracicsurgery.However,
insomesettingstheriskofVTEremainsuncertain,andtherehavenotbeengoodrandomizedclinicaltrials
demonstratingeffectivenessofanyparticularformofVTEprophylaxis.Theseincludevascularsurgery,laparoscopic
surgery,kneearthroscopyintheabsenceofmorecomplicatedsurgery,electivespinesurgery(eg,spinalfusion[72]),
shoulderandelbowsurgery[73],isolatedlowerextremityfractures,Achillestendonrupturerepair[74],andpodiatric
surgery[25].
ModerateriskpatientsModeraterisksurgicalpatientshavebeendefinedasthoseundergoinggeneraland
abdominalpelvicsurgerywithaCapriniscoreof3to4,orthoseundergoingplasticandreconstructivesurgerywitha
Capriniscoreof5to6.TheirestimatedbaselineriskofVTEintheabsenceofprophylaxisisestimatedtobe
approximately3percent.
Patientsundergoinggeneralgynecologic,urologic,thoracic,anklefracture,orneurosurgicalproceduresusuallyfallinto
themoderateriskcategory[24,25,75,76].
HighriskpatientsHighrisksurgicalpatientshavebeendefinedasthoseundergoinggeneralandabdominal
pelvicsurgerywithaCapriniscoreof5ormore,orthoseundergoingplasticandreconstructivesurgerywithaCaprini
scoreof7to8.TheirestimatedbaselineriskofVTEintheabsenceofprophylaxisisestimatedtobeapproximately6
percent.Examplesofpatientsinthehighriskgrouparethoseundergoinghiporkneearthroplasty,pelvicorhipfracture
surgery,colorectalsurgery,majortrauma,spinalcordinjury,orcancersurgery[25,77,78].
OrthopedicsurgeryAnumberoffactorsincreasetheriskofVTEduringorthopedicsurgery,includingthe
supinepositionontheoperatingtable,theanatomicpositionoftheextremityinapatientundergoingkneearthroplasty,
andtheuseofathightourniquet.Asexamples,internalinjurymayresultfrompositioningoftheextremity,and
compressionofthefemoralveinmayoccurduetoflexionandadductionofthehipduringsurgeryonthisjoint.
Theuseofprophylacticanticoagulationinhighrisksettingssubstantiallyreduces,butdoesnotcompletelyeliminate,
theriskofVTE.Onemetaanalysisof47studiesin44,844patientswhounderwenteithertotalorpartialknee(TPKA)
ortotalorpartialhip(TPHA)arthroplastyandreceivedcurrentlyapprovedVTEprophylaxisfoundthattheratesof
symptomaticVTEpriortohospitaldischargewereapproximately1.1and0.53percent,respectively[79].Becausethe
endpointwassymptomaticVTEduring(butnotafter)hospitalization,thetruerateofrelevantVTEeventswas
presumablyunderestimated.
TheimportanceofearlyambulationinreducingtheincidenceofVTEfollowingtotalkneeandtotalhiparthroplastyhas
alsobeenemphasized[8082].Asanexampleoftherelevantissues,inacasecontrolstudyof593patients
undergoingtotalkneearthroplasty(TKA)thefollowingfactorsweresignificantlyassociatedwiththedevelopmentof
postoperativesymptomaticVTEpriortohospitaldischarge[83]:

BilateralsimultaneousTKAratherthanunilateralTKA(OR4.295%CI1.99.1)
UseofFDAapprovedpharmacologicprophylaxisversusmechanicalprophylaxis(OR0.595%CI0.30.8)
Ambulationonorbeforethesecondpostoperativeday(OR0.395%CI0.10.9)
Severeobesity(BMI>35versusBMI35)wasnotasignificantpredictorforVTE(OR0.995%CI0.51.6)

ObesepatientsandthoseundergoingbariatricsurgeryTheobesesurgicalpatientisconsideredtobeat
moderatetohighriskforVTE,withanestimatedCapriniscoreof4ormoreforthoseundergoingbariatricsurgery
[68,84].However,thepreferredanticoagulant(eg,unfractionatedversusLMWheparin)andappropriateprophylactic
anticoagulationdosingarebothunclearavailablestudiesonthissubjecthavebeenconsideredtobeoflowquality
[68,85,86].
Amorecompletediscussionofthissubjectispresentedseparately.(See"Bariatricsurgery:Intensivecareunit
managementofthecomplicatedpostoperativepatient",sectionon'Anticoagulantdosing'and"Bariatricsurgery:
Postoperativeandlongtermmanagementoftheuncomplicatedpatient",sectionon'Venousthromboembolism'.)
PREVENTIONOFVTE
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OverallapproachesTherearetwoapproachestothepreventionoffatalpulmonaryembolism:
PrimaryprophylaxisPrimaryprophylaxisiscarriedoutusingeitherdrugsorphysicalmethodsthatare
effectiveforpreventingDVT.
SecondarypreventionSecondarypreventioninvolvestheearlydetectionandtreatmentofsubclinicalvenous
thrombosisbyscreeningpostoperativepatientswithobjectiveteststhataresensitiveforthepresenceofDVT.
However,nosinglescreeningmethod(eg,contrastvenography,ultrasonography,MRIvenography)hasfounduniversal
acceptanceforsecondaryprevention[87,88].Accordingly,primaryprophylaxisispreferredinmostclinical
circumstancesitismorecosteffectivethantreatmentofcomplicationsoncetheyoccur[89].Secondaryprevention
withscreeningisreservedforpatientsinwhomprimaryprophylaxisiseithercontraindicatedorshowntobeineffective.
PrimaryprophylaxisThecharacteristicsofapreferredprimaryprophylacticmethodincludeamethodthatiseasy
toadminister,issafeandeffectivewithlimitedornoneedforlaboratorymonitoring,thatiscosteffective.
SelectingprophylaxisoptionsOptionsforprimaryVTEprophylaxisincludepharmacologicand/ormechanical
methods,whichhavevariableefficacyandbleedingrisk.Ingeneral,thepreferredmethodofprophylaxisisdependent
upontheriskofpostoperativeVTEwhichis,inturn,determinedbythetypeofsurgeryandtheCapriniscore(table2):
EarlyandfrequentambulationispreferredinsurgicalpatientsatverylowriskofVTE(eg,patientsundergoing
generalandabdominalpelvicsurgerywithaCapriniscoreofzeroORplastic/reconstructivesurgerywitha
Capriniscoreofzerototwo).(See'Verylowriskpatients'above.)
Mechanicalmethodsarepreferredinpatientswithacontraindicationtopharmacologicprophylaxisandinlowrisk
surgicalpatients(eg,patientsundergoinggeneralandabdominalpelvicsurgerywithaCapriniscoreof1to2OR
plastic/reconstructivesurgerywithaCapriniscoreof3to4).(See'Lowriskpatients'aboveand'Mechanical
methodsofthromboprophylaxis'below.)
PharmacologicprophylaxisispreferredinsurgicalpatientsatmoderateandhighriskofVTE(eg,patients
undergoinggeneralandabdominalpelvicsurgerywithaCapriniscoreof3ORplastic/reconstructivesurgery
withaCapriniscoreof5).(See'Moderateriskpatients'aboveand'Highriskpatients'aboveand
'PharmacologicagentsforVTEprevention'below.)
Combinedpharmacologicandmechanicalmethods(usuallyintermittentpneumaticcompression)ratherthan
eithermethodalonecanbeconsideredinsurgicalpatientsassessedtobeatveryhighriskofVTE(eg,highrisk
cancersurgeryandmultipleadditionalriskfactors).(See'PharmacologicagentsforVTEprevention'belowand
'Intermittentpneumaticcompression'below.)
Selectingapharmacologicagentwilldependonitsefficacyandsafetyaswellasthepresenceofcomorbidities(eg,
renalinsufficiency),andpatientpreferencesandvalues.Ingeneral,thefollowingapplies:
LMWheparinsandfondaparinuxarepreferredratherthanUFHorotherpharmacologicagents,particularlyinhigh
risksurgicalpatients(eg,totalhipandkneereplacement)duetotheirprovenefficacyandextendedexperiencein
thispopulation.(See'Lowmolecularweightheparin'belowand'Fondaparinux'below.)
LowdoseUFHisareasonablealternativetoLMWheparinforsurgicalpatientsinwhomthereisa
contraindicationtoLMWheparin(eg,renalinsufficiency)orforpatientsinwhomcostisanissue.(See'Lowdose
unfractionatedheparin'below.)
WarfarinmaybeconsideredasanalternativetoLMWheparinandUFHwhendelayedprophylaxisisdesiredin
surgicalpatientsaftertotalhiporkneereplacement.(See'Warfarin'below.)
DirectthrombinandfactorXainhibitorshavenotbeenstudiedinthegeneralsurgicalpopulationbutmaybe
alternativestoLMWheparininorthopedicpatientswhohaveundergoneatotalhiporkneereplacement.These
agentshavenotbeencomparedwithUFHoraspirin.(See'DirectthrombinandfactorXainhibitors'below.)
Aspirincanbeconsideredfororthopedicpatientswhohaveundergoneatotalhiporkneereplacementandarenot
candidatesforotheranticoagulants.(See'Aspirin'below.)
VTEprophylaxisinspecialsurgicalpopulationsisdiscussedseparatelyinthefollowingssections:
Patientsundergoinggynecologicsurgery(see"Overviewofpreoperativeevaluationandpreparationfor
gynecologicsurgery",sectionon'Thromboprophylaxis')
Patientsthatarecriticallyill(see"Preventionofvenousthromboembolicdiseaseinacutelyillhospitalized
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medicaladults",sectionon'Selectionofmethodofprophylaxis')
Patientsundergoingbariatricsurgery(see"Bariatricsurgery:Postoperativeandlongtermmanagementofthe
uncomplicatedpatient",sectionon'Venousthromboembolism'and"Bariatricsurgery:Intensivecareunit
managementofthecomplicatedpostoperativepatient",sectionon'Prophylaxisforvenousthromboembolic
events')
TimingofcommencementofprophylaxisProphylaxisisideallystartedduringhospitalization,eitherbeforeor
shortlyaftersurgery,andcontinuedatleastuntilthepatientisfullyambulatory[25,90,91].Theadministrationof
thromboprophylaxisincloseproximitytosurgeryhasbeenshowntoenhanceitsefficacyinasystematicreviewthat
comparedprophylaxiswithLMWheparinversuswarfarin[9294].
AlargeriskreductioninvenographicallydetectedDVTwasobservedwhentheLMWheparindalteparinwas
initiatedathalftheusualhighriskdoseinproximitytototalhipreplacement(ie,eitherwithintwohoursbefore
surgeryorfourtosixhoursaftersurgery).
WhenLMWheparinwasstartedeither12hoursbeforesurgeryor18to24hoursaftersurgery,theefficacy
advantageofLMWheparinoverwarfarinwasnotobserved.However,startingLMWheparinwithintwohoursof
surgerywasassociatedwithanincreasedriskofmajorbleeding.
ValuesandpreferencesTheconceptofvaluesandpreferenceswasintroducedstartingwiththe2004ACCP
Guidelines[38].Thisissuerequiresconsiderablethoughtbyboththeclinicianandthepatient.Asexamples:
Inthetreatmentofestablishedpulmonaryembolism(PE),agreatervalueisnormallyplacedonthepreventionof
deathfromrecurrentPEthanfromtherelativelylowriskofbleedingfromtheuseofanticoagulation.
Inorthopedicsurgery,greatervalueisplacedontheavoidanceofbleedingfromanticoagulationovertherelatively
lowfrequencyofdeathfrompulmonaryembolismifthromboprophylaxisisnotused.ThusinNorthAmericaa
commonregimenwithLMWheparinistostartat18to24hourspostoperatively[93].Italsoexplainswhytheuse
ofwarfarin,withitsdelayedonsetofeffectiveanticoagulation,remainspopular,particularlyintheUnitedStates.
AsystematicreviewandmetaanalysisofrandomizedclinicaltrialsevaluatingVTEprophylaxisinpatients
undergoingelectivecranialneurosurgeryhasestimatedthatforevery1000patientswhoreceiveheparin
prophylaxis,91VTEeventswillbeprevented[95].Approximately35ofthesewillbeproximalDVTorPE,and
only9to18willbesymptomatic.Ontheotherhand,7intracerebralhemorrhagesand28moreminorbleedswere
estimatedtooccurifaheparinpreparationisemployed,versusnoneifamechanicalmethodof
thromboprophylaxisisused.Suchanalysescanbeemployedtobetterinformcliniciansandtheirpatientsabout
DVTprophylaxisoptionsforcranialneurosurgicalprocedures.(See'Mechanicalmethodsofthromboprophylaxis'
below.)
DefinitionofmajorbleedingThecommonlyusedtraditionalclassificationformajorbleedingisrecommended
andhasbeenapprovedbytheInternationalSocietyforThrombosisandHemostasis[96]:
Fatalbleeding,and/or
Symptomaticbleedinginacriticalareaororgan,and/or
Bleedingcausingafallinhemoglobinof2g/dLorleadingtotransfusionoftwoormoreunitsofwholebloodor
redcells
ExtendedprophylaxisExtendedVTEprophylaxisisofferedtopatientsathighriskforVTEtoaccommodateearlier
dischargeandinrecognitionthatVTEcanoccurdaystoweekspostdischarge[97,98].Evidenceisstrongestfor
patientswhohaveundergonemajororthopedicsurgery(totalhipreplacement[THR],totalkneereplacement[TKR],hip
fracturesurgery[HFS]),andcancerandmajorabdominalsurgery.Lowmolecularweight(LMW)heparinisthepreferred
agent.Theoptimaldurationofextendedprophylaxisisunknownbutisusuallygivenbeyond10daysandupto35days
followingmajororthopedicsurgeryandforaperiodofthreetofourweeksforselectedhighriskpatientswhoundergo
majorabdominaland/orpelvicsurgeryforcancer.
Forpatientswithmajororthopedicsurgery,inparticularTHR,manyrandomizedtrialsandmetaanalyseshaveshown
thatcomparedtoplaceboandotheragents(eg,warfarinandaspirin),extendedprophylaxis(28to35days)withLMW
heparinreducestherateofVTEwithoutexcessbleeding[97,99106].
AlthoughLMWheparinissuperior,otheragentsmaybepreferredincertainsettings.Forexample,LMWheparinis
costlyandsomepatientscannottolerateorselfadministerLMWheparininjections.Studiescomparingthesafetyand
efficacyofwarfarinandaspirintoLMWheparinaredescribedbelow:
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Onerandomizedtrialof1279patientswhohadundergoneTHRshowedthat,comparedtoLMWheparin,six
weeksofwarfarinresultedinasimilarrateofVTE(2versus3percent)[107].However,majorbleedingwas
higherwithwarfarin(6versus1percent).
Inonemulticentercontrolledtrial(EPCAT),778patientswhohadundergoneTHRandhadreceivedaninitial10
daysofLMWheparin(dalteparin)wererandomlyassignedtoeitherextendedprophylaxiswithLMWheparinorto
aspirin[108].ComparedwithLMWheparin,aspirinwasassociatedwithasimilarrateofVTE(1.3foraspirin
versus0.3percentforLMWheparin)andbleedingevents(0.5versus1.3percent)at28days.However,thistrial
wasstoppedearlyduetoslowenrollmentandtheeffectsizewasbasedonasmallnumberofevents,limiting
thequalityofthedata.
Thus,weandotherssupporttheuseofLMWheparinasthepreferredagentforextendedprophylaxisafterTHR[68].
AlthoughtheevidenceisnotasstrongforpatientswithTKRandHFS,smalltrialsandtherationalethatthesepatients
arealsoathighriskforVTEsupporttheuseofextendedprophylaxisinthispopulationaswell[68,99].
Thedurationofextendedprophylaxisfollowingorthopedicsurgeryhasvariedbetweenstudies.However,mosttrials
supportprophylaxisbeyond10daysandupto35daysfollowingsurgery[97,99102,105,107,109].
Patientsundergoingcancersurgeryormajorabdominalsurgeryalsobenefitfromextendedprophylaxis,most
commonlyforaperiodoffourweeks[110114].Onerandomizedstudyof1113patientspostabdominalorpelvic
surgeryforcancerreportedthat,comparedtoeightdaysofLMWheparin,fourweeksdecreasedmajorVTE(4.6
versus0.8percent)withoutincreasinghemorrhagiccomplications[113].Inanotherstudyofpatientswhohad
undergonemajorabdominalsurgery,theadministrationofLMWheparinforfourweekssignificantlyreducedtherateof
VTE(16.3versus7.3percent),withoutincreasingtheriskofbleeding[112].Extendedprophylaxisforcancersurgery
patientshasalsobeenrecommendedinthe2012guidelinesissuedbytheAmericanCollegeofChestPhysicians
(ACCP),theNationalComprehensiveCancerNetwork(NCCN),andtheAmericanSocietyofClinicalOncology
(ASCO)[68,114,115].(See"Riskandpreventionofvenousthromboembolisminadultswithcancer",sectionon
'Surgicalpatients'.)
ComparisonofagentsComparisonsofagentsacrossstudiesofhiporkneesurgeryhavebeendifficult,sincethe
drugsunderinvestigationandthedosingscheduleshavevariedfromoneclinicaltrialtoanother.Evenwithinthesame
clinicaltrialtherecanbeconsiderableintercentervariability.Inaddition,bleedingrateshavevariedquitewidelyacross
studies,atleastinpartbecausedifferentdefinitionsforbleedinghavebeenused[116].(See'Definitionofmajor
bleeding'aboveand'Rivaroxaban'below.)
AnumberofrandomizedtrialshavecomparedLMWheparinwithUFH,warfarinoracenocoumarol,orfondaparinuxin
patientsundergoingtotalhipreplacementsurgery,andtoalesserextenttotalkneereplacementsurgery.Ameta
analysiscomparingvitaminKantagonistsversusLMWheparinforthepreventionofVTEinorthopedicsurgery
indicatedthatthevitaminKantagonistsarelesseffectivethanLMWheparin,withoutanysignificantdifferencein
bleedingrisk[117].
Ingeneral,LMWheparinhasbeenshowntobesuperiortoUFHorwarfarin,butinferiortofondaparinuxintermsof
efficacy,withsimilarbleedingratesinpatientsundergoingtotalhiportotalkneereplacementsurgery.
TheuseoftheLMWheparinenoxaparindiffersbetweenregions[22].Thus:
InNorthAmerica,enoxapariniscommonlyusedinthedoseof30mgtwicedailystarting12to24hours
postoperatively.
InEurope,enoxaparinatadoseof40mgisstarted12hourspreoperativelyandisthengivenoncedaily.
OtherLMWheparinpreparationshaveusuallybeengiveninaoncedailydosage,startingpostoperatively.
AmetaanalysisinpatientsundergoingcancersurgeryconcludedthattherewasnodifferencebetweenLMWheparin
andUFHintermsofefficacy,DVTlocation,orbleedingcomplications[118].
ACochranereviewoftheuseofLMWheparintopreventVTEinpatientswithlowerlegimmobilizationconcludedthat
LMWheparininoutpatientssignificantlyreducedtheincidenceofVTE[119].Afurthermetaanalysisreviewedtheuse
ofintermittentpneumaticcompression(IPC)withorwithoutpharmacologicprophylaxisusedintheformofLMW
heparin.Itwasshownthat,comparedwithIPCalone,combinedprophylacticmodalitiesdecreasedtheincidenceof
VTE[120].
Inpatientsundergoingneurosurgicalprocedures,LMWheparinwasshowntobesuperiortoIPC[121,122].Inpatients
sufferingmajortrauma,LMWheparinwassuperiortoUFHinthepreventionofbothtotalandproximalDVTs[123].
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PHARMACOLOGICAGENTSFORVTEPREVENTIONAnumberofpharmacologicagentsarenowavailablefor
VTEpreventioninsurgicalpatients,includingunfractionatedheparin,theLMWheparins,fondaparinux,thevitaminK
antagonists,andtheneworalantithromboticagentsrivaroxaban,dabigatran,andapixaban.Thesewillbediscussed
below.Whenavailable,metaanalysesofthecomparativeeffectivenessamongthesevariousagentswillalsobe
discussed[124128].
LowdoseunfractionatedheparinLowdosesubcutaneousunfractionatedheparin(UFH)forprophylaxisofVTEis
usuallygiveninadoseof5000unitstwohourspreoperativelyandthenevery8to12hourspostoperatively(ie,either
twiceorthreetimesdaily).
Anearlyprospectiverandomizedstudyofover4000patientsfoundthatlowdoseheparinreducedtheincidenceoffatal
PEinpatientsundergoingmajorsurgicalproceduresfrom0.7to0.1percentcomparedwithcontrols[129].Pooleddata
frommetaanalysesconfirmedthatlowdoseUFHreducedtheincidenceofallDVT,proximalDVT,andallPE
includingfatalPE[20,21,130,131].Mostofthepatientsinthesetrialsunderwentabdominalorthoracicsurgery
(particularlyforgastrointestinaldisease),butsomepatientshadgynecologicorurologicsurgery,mastectomy,or
vascularprocedures[20,21].
InadditiontotherelativelylowsideeffectprofileoflowdoseUFH,itsadvantagesarethatitisrelativelyinexpensive
andeasilyadministered,andanticoagulantmonitoringisnotrequired.However,theplateletcountshouldbemonitored
regularlyinallpatientsreceivinglowdoseUFHtodetectthedevelopmentofheparininducedthrombocytopenia
[132,133].(See"HeparinandLMWheparin:Dosingandadverseeffects",sectionon'Plateletcountmonitoring'.)
LowmolecularweightheparinAnumberoflowmolecularweightheparin(LMWheparin)preparationsare
available.Thesedrugshavetheadvantagethattheycanbegivensubcutaneouslyonceortwicedailyataconstant
dosewithoutlaboratorymonitoringfortherapeuticeffect.However,creatinineclearanceshouldbeintermittently
monitoredduringthehospitaladmissionforpatientsreceivingLMWheparin.Inaddition,thereisalowerincidenceof
heparininducedthrombocytopeniathanwithUFH.(See"HeparinandLMWheparin:Dosingandadverseeffects",
sectionon'LMWheparin'and"Lowmolecularweightheparinforvenousthromboembolicdisease",sectionon
'PreventionofVTE'.)
Asanexample,inarandomizeddoubleblindstudyofpatientsundergoinghipreplacementsurgery,heparininduced
thrombocytopenia(HIT)occurredin9of332patients(2.7percent)receivingUFHcomparedwithnoneof333patients
receivingLMWheparin[132].AmetaanalysisofallstudiescomparingtheincidenceofHIToccurringafterexposureto
UFHversusLMWheparinafteranysurgicalinterventionconfirmedthattheincidenceofHITissignificantlylesswith
LMWheparin(RR0.20,95%CI0.040.90)[134].However,thisconclusionislimitedbyascarcityofhighquality
studiesincludingHITasanoutcome.(See"Clinicalpresentationanddiagnosisofheparininducedthrombocytopenia".)
TheLMWheparinshavebeenextensivelystudiedforthepreventionofVTE.Studiesinsurgicalpatientshaveincluded
thoseundergoinggeneralsurgery,includinggynecologicandurologicsurgery[22,23,135,136],orthopedicsurgery
includingtotalhipandkneereplacementsurgery[94,99,100,137143],hipfracture[109,144],lowerlegfractures
[119,145147],arthroscopy[148150],traumaincludingspinalcordinjuryandneurosurgery[121123,151155],and
cancersurgery[110112,118,156158].MetaanalysesofLMWheparininthepreventionofVTEingeneralsurgeryhave
shownefficacytobeatleastasgoodaswithUFH,withequalsafety[22,23].
Inmostcountries,LMWheparinistheprophylacticagentofchoiceforpreventingVTEinhighriskpatients.
FondaparinuxThedosingoffondaparinuxisdiscussedelsewhereinUpToDate,butissuesrelatedtoitsusein
surgicalpatientswillbereviewedhere.(See"Fondaparinux:Dosingandadverseeffects".)
FondaparinuxhasbeenevaluatedinthepreventionofVTEinpatientsundergoingorthopedicsurgeryandgeneral
surgery:
TotalhipreplacementOnephaseII[159]andtwophaseIIItrials[140,160]havebeencompletedinwhich
fondaparinux,indosesrangingfrom2.5to3mg/daysubcutaneously,startingfourtoeighthourspostoperatively,
wascomparedwith30mgofenoxaparinsubcutaneouslyevery12hoursstarting12to24hourspostoperatively
(PENTATHLONtrial)[140,159],orwith40mgofenoxaparingiven12hoursbeforesurgery,followedby40mg12
to24hoursaftersurgeryanddailythereafter(EPHESUStrial)[160].Inallthreestudies,fondaparinuxwasmore
effectivethanenoxaparininpreventingpostoperativeVTE,withrelativeriskreductionsinthephaseIIandIII
trialsrangingfrom26to81percent.Ratesofmajorbleedingrangedfrom1.8to4.1percentforfondaparinuxand
1.0to3.5percentforenoxaparin.
Ina2002metaanalysisoffouravailabletrials,itwasconcludedthattheefficacyoffondaparinuxwassuperiorto
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thatofenoxaparin[161].Inthesestudies,majorbleedingoccurredmorefrequentlyinfondaparinuxtreated
subjects,buttherewasnotanincreaseinbleedingleadingtodeathorreoperationorbleedingintoacriticalorgan
withfondaparinuxcomparedwithenoxaparin[161].Mostofthepatientswhobledhadtheirinitialfondaparinux
injectionlessthaneighthourspostoperatively.
Asinglecenter,retrospectivecohortstudyin5061consecutiveunselectedpatientsundergoingmajororthopedic
surgeryreportedthatthromboprophylaxiswithrivaroxabanwasassociatedwithsignificantlyfewerepisodesof
symptomaticVTEandmajorbleedingeventsthanfondaparinux[162].Prospectivecomparisonstudiesare
warrantedtoconfirmthesefindings.(See'Rivaroxaban'below.)
HipfractureInaphaseIIItrial,patientsundergoingsurgeryforfractureoftheupperthirdofthefemurwere
randomlyassignedtotreatmentwithfondaparinux(2.5mgoncedailystartingfourtoeighthourspostoperatively)
orenoxaparin(40mg/daystarting12hourspreoperatively)[109].TheincidenceofVTEbyday11was
significantlylowerwithfondaparinux(8.3versus19.1percent).Therewerenosignificantdifferencesinthe
incidenceofdeathormajorbleeding.
Thebenefitofthromboprophylaxiswithfondaparinuxforonemonth,ratherthanoneweekwasstudiedina
doubleblind,multicentertrial[144].Allpatientsreceivedfondaparinuxforthefirstsixtoeightdays,following
whichtheywererandomlyassignedtoreceivefondaparinux(2.5mg/day)orplaceboforanadditional19to23
days.Comparedwithoneweekoffondaparinux(followedbythreeweeksofplacebo),onemonthoffondaparinux
resultedinahighlysignificantreductionintheincidenceofdocumentedVTEfrom35to1.4percent(relativerisk
reduction96percent,95%CI:87100percent),aswellasan87percentreductionintheriskofsymptomatic
VTE.Althoughtherewasanonsignificanttrendtowardmoremajorbleedinginthegrouptreatedwithonemonth
offondaparinux,asjudgedbythebleedingindex,therewerenodifferencesbetweenthetwogroupsinthe
incidenceofbleedingintocriticalorgans,orbleedingleadingtodeathorreoperation.
KneesurgeryInaphaseIIItrial,patientsundergoingmajorkneesurgerywererandomlyassignedtotreatment
withfondaparinux(2.5mgoncedailystartingfourtoeighthoursaftersurgery)orenoxaparin(30mgtwicedaily
starting12to24hoursaftersurgery)[143].TheincidenceofVTEbyday11wassignificantlylowerwith
fondaparinux(12.5versus27.8percent).Majorbleedingoccurredmorefrequentlyinthefondaparinuxgroup,as
judgedbythe"bleedingindex"(seeabove),buttherewerenosignificantdifferencesbetweenthetwogroupsin
theincidenceofclinicallyrelevantbleeding(eg,fatalbleeding,bleedinginacriticalorgan,orbleedingrequiring
reoperation).
AbdominalsurgeryInthedoubleblindrandomizedPEGASUStrial,patientsscheduledformajorabdominal
surgeryundergeneralanesthesiawererandomlyassignedtooneofthefollowingtwotreatments[136]:
Fondaparinux(2.5mgsubcutaneouslydailyforfivetoninedays,startingsixhoursaftersurgery),or
Dalteparin(2500unitssubcutaneouslytwohoursbeforesurgeryand12hoursafterthepreoperative
administration,followedby5000unitssubcutaneouslydailyforfivetoninedays)
Among2048evaluablepatients,therateofVTEforthosetreatedwithfondaparinuxordalteparinwas4.6versus
6.1percent,respectively,forarelativeriskreductionof25percent(95%CI9to+48),meetingthepredetermined
criterionfornoninferiorityoffondaparinux.Majorbleedingwassimilarinthetwotreatmentarms(3.4versus2.4
percent,respectively).
IntheAPOLLOStudy,patientsage40undergoingmajorabdominalsurgeryofatleast45minutesdurationwere
randomlyassignedtoreceivepostoperativeVTEpreventionwithintermittentpneumaticcompressionpluseither
placeboorfondaparinux(2.5mgoncedailysubcutaneouslyforfivetoninedays,startingsixtoeighthours
postoperatively)[163].Thevastmajority(82percent)ofthesubjectshadatleastoneVTEriskfactoroverand
abovetheirageandtheabdominalsurgery.FondaparinuxsignificantlyreducedtheVTErateversusthatseen
afterplacebo(1.7versus5.3percentoddsratioreduction70percent,95%CI2887).Majorbleedingwasmore
frequentafterfondaparinux(1.6versus0.2percent),althoughnoneofthebleedingeventswerefatalorinvolveda
criticalorgan.
WarfarinOralanticoagulationwithvitaminKantagonists(VKA)suchaswarfarinoracenocoumarol,canbe
commencedpreoperatively,atthetimeofsurgery,orpostoperativelyforthepreventionofVTE[164].However,therapy
startedatthetimeofsurgeryorintheearlypostoperativeperiodmaynotpreventsmallvenousthrombifromforming
becausetheanticoagulanteffectoftheVKAsisnotachieveduntilthethirdorfourthdayoftreatmentwiththese
agents.(See"BiologyofwarfarinandmodulatorsofINRcontrol",sectionon'Mechanismofaction'.)

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Nonetheless,warfarinappearstoeffectivelyinhibitextensionofsuchthrombiifpresent,therebypreventingclinically
importantVTE.BecauseofitsdelayedonsetofactionalongwithbleedingratessimilartothoseseenwithLMW
heparin,warfarinhasbeenfavoredasathromboprophylacticagentbyorthopedicsurgeonsintheUnitedStates.
WarfarinhasbeencomparedwithLMWheparininpatientsundergoingtotalhiporkneereplacementsurgery
[94,165,166].MoststudieshaveshownsuperiorbenefitwithLMWheparinwithoutanyincreaseinbleedingrates.Ina
comparisonofwarfarinwithintermittentpneumaticcompressionaftertotalhipreplacement,warfarinwassignificantly
moreeffective[13].Inoneearlierstudy,warfarinwassuperiortoaspirinorplaceboforthepreventionofDVTfollowing
surgeryforhipfracture[167].
WarfarinreducestheincidenceofVTEwhenusedforfourweeksfollowingtotalhipreplacement.Whencomparedwith
LMWheparin,eachgivenforfourweekspostoperativelyaftertotalhipreplacement,warfarinshowedequalefficacy
butasignificantlyincreasedincidenceofmajorbleeding[107].
DirectthrombinandfactorXainhibitorsOrallyactiveagentsthatspecificallyinhibiteitheractivatedfactorXor
activatedfactorII(thrombin)haveundergoneextensiveevaluationwithfavorableresultsfromanumberofphaseIII
studies.Rivaroxabanandapixaban,factorXainhibitors,anddabigatranetexilate,afactorIIainhibitor(directthrombin
inhibitor),havebeenapprovedforusebyregulatoryagentsintheUnitedStatesandseveralothercountries.Froma
practicalstandpoint,theseagentsareappealingbecauseoftheireaseofadministration,asapillinsteadofa
subcutaneousinjection.Whiletheseagentsaresuperiortoplacebo[168],theirbenefitscomparedwithother
anticoagulantsremainuncertain.Thesafetyandefficacyofindividualagentsaresummarizedbelow.
RivaroxabanRivaroxabanisaspecificinhibitorofactivatedfactorXwithexcellentoralbioavailabilityanda
halflifeofapproximatelyninehours.Itisprimarilyexcretedrenally,althoughsomeisexcretedthroughthe
gastrointestinaltract.Asaresult,cautionisrecommendedinpatientswithrenalinsufficiencyitsuseis
contraindicatedinpatientswithacreatinineclearance<30mL/min.Itisalsocontraindicatedinpatientswithsevere
hepaticdiseaseanddosagereductionisrecommendedinpatients>65yearsofage.(See"Directoralanticoagulants:
Dosingandadverseeffects",sectionon'Rivaroxaban'.)
Twostudieswerecarriedoutinpatientsundergoingtotalhipreplacement.Thefirstcomparedrivaroxaban10mgorally
oncedailywithenoxaparin40mgoncedailysubcutaneouslystarting12hourspreoperatively,bothfor354days
(RECORD1)[169].Thesecond(RECORD2)comparedoralrivaroxaban10mgoncedailyfor354dayswith
enoxaparin40mgoncedailystarting12hourspreoperativelyfor122days[170].
InRECORD1,rivaroxabanshowedsuperioritytoenoxaparinforthereductionoftotalVTE,majorVTE(ie,a
compositeofproximalDVT,nonfatalPE,orVTErelateddeath),withnodifferenceinmajorbleedingevents
[169].
RECORD2showedsuperiorityofrivaroxabanintheincidenceoftotalVTE,majorVTE,andproximalordistal
DVT,andnotablyintheincidenceofsymptomaticVTE[170].
Inpatientsundergoingtotalkneereplacement(RECORD3),rivaroxaban10mgorallyoncedailywascompared
withenoxaparin40mgsubcutaneouslydailystarting12hourspreoperatively,witheitheragentcontinuedfor12
2days[171].Inthisstudy,rivaroxabanwassuperiortoenoxaparininthereductionoftotalVTE,majorVTEand
distalDVT,andsignificantlyreducedtheincidenceofsymptomaticVTE.
IntheRECORD4study,patientsundergoingtotalkneereplacementwererandomlyassignedtoreceiveeither
rivaroxaban10mgdailyPOorenoxaparin30mgtwicedailystarting12to24hourspostoperatively,withboth
givenfor124days[172].TherewasasignificantdecreaseintotalVTEwithrivaroxaban,butthedifferencein
theincidenceofmajorVTEandsymptomaticVTEdidnotreachstatisticalsignificance.
ApooledanalysisoffourphaseIIIstudieswasperformedcomparingrivaroxaban10mg/daywithenoxaparin(either40
mg/dayor30mgtwiceperday)forthromboprophylaxisaftertotalhiporkneereplacementsurgery[173].Thefollowing
resultswereobtained:
Comparedwithenoxaparin,thromboprophylaxiswithrivaroxabanwasassociatedwithsignificantlyfewer
symptomaticVTEeventsandallcausemortality(oddsratio0.4895%CI0.300.76)duringthetreatmentperiod.
Thecompositeofmajorandnonmajorclinicallyrelevantbleedingduringthetreatmentperiodwas2.8percent
withrivaroxabanversus2.5percentwithenoxaparin(oddsratio1.1795%CI0.931.46).
Inallstudieswithrivaroxabantherewasnosignificantelevationofliverenzymesorincreaseinthrombotic
eventsduringthetreatmentperiod.
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AretrospectivecohortstudyfromtheORTHOTEPregistryevaluatedtherelativeefficacyandsafetyofrivaroxaban
versusfondaparinuxthromboprophylaxisin5061unselectedconsecutivepatientsundergoingmajororthopedicsurgery.
Resultsincludedthefollowing[162]:
RatesofsymptomaticVTEweresignificantlylowerforrivaroxaban(2.1versus5.6percent)
Ratesofseverebleedingweresignificantlylowerforrivaroxaban(2.9versus4.9percent)
Themeanlengthofhospitalizationwassignificantlyshorterintherivaroxabangroup(8.3versus9.3days).
AsimilarretrospectivecohortstudyfromtheORTHOTEPregistryevaluatedtherelativeefficacyandsafetyof
rivaroxabanversuslowmolecularweightheparinthromboprophylaxisin5061unselectedconsecutivepatients
undergoinghipandkneereplacementsurgery.Resultsincludedthefollowing[174]:
RatesofsymptomaticVTEweresignificantlylowerforrivaroxaban(2.1versus4.1percent)
Ratesofmajorbleedingweresignificantlylowerforrivaroxaban(2.9versus7.0percent)
Themeanlengthofhospitalizationwassignificantlyshorterintherivaroxabangroup(8.3versus11.1days).
Prospectivestudieswillberequiredinordertoconfirmbothofthesefindings.
DabigatranetexilateDabigatranetexilateisanorallyabsorbedprodrugwithapproximately5percent
bioavailability.Itisconvertedtotheactiveagentdabigatran,whichhasahalflifeofapproximatelyeighthoursaftera
singledoseand17hoursaftermultipledoses.Dabigatranisadirectthrombininhibitorthatisactiveagainstbothfree
andclotboundthrombin.Theactivityofdabigatranisdirectedagainsttheconversionoffibrinogentofibrin,butitalso
inhibitsplateletactivationbythrombinandtheactivationofclottingfactorsV,VIII,andXIbythrombin.(See"Direct
oralanticoagulants:Dosingandadverseeffects",sectionon'Dabigatran'.)
ForthepreventionofVTE,dabigatranhasbeenstudiedinpatientsundergoingtotalhiportotalkneereplacement
surgery.BasedonaphaseIIdosefindingstudyinpatientsundergoingtotalhiporkneereplacementsurgery,asafe
andeffectivedailydosingofdabigatranetexilatewassuggestedtobeintherangebetween100and300mg/day
[175,176].Ametaanalysisofavailableefficacyandsafetydatafromthreetrialshasconcludedthatdabigatran,atthe
recommendeddoseof220mgoncedaily,wasnoninferiortoenoxaparin(40mg/day)forVTEprophylaxisaftertotal
kneeortotalhiparthroplasty,withasimilartoxicityprofile[177].
Inpatientsundergoingtotalkneereplacementsurgery(theREMODELstudy)oraldabigatran150mgor220mgdaily
wascomparedwithenoxaparin40mgdailystarting12hourspreoperatively,withmandatoryvenographyatday6to
10andfollowupfor10to14weeks[178].Inthedabigatran150mg/daygroupthefirstdosewasgivenonetofour
hourspostoperativelyatadoseof75mgandthereafter150mgonce/day,andinthe220mg/daydabigatrangroupthe
initialdosewas110mg,followedby220mg/day.
Thistrialwasdesignedasanoninferioritystudyandachievednoninferioritycomparedwithenoxaparinforthe
preventionoftotalVTEandreductionofallcausemortality.Therewasnodifferenceintheincidenceofsymptomatic
VTE.Bleedingrateswerelowandcomparableinbothgroups,with89percentofmajorbleedingeventsbeingnotedat
thesurgicalsite.
TheRENOVATEtrialinpatientsundergoingtotalhipreplacementsurgerycomparedoraldabigatran150mg/dayor220
mg/daystartingwithinonetofourhourspostoperativelywithenoxaparin40mgoncedailystarting12hourspre
operatively[179].Alltreatmentcontinuedfor28to35days,atwhichtimevenographywasdone[179].Forthe
compositeendpointoftotalVTEandallcausemortality,botharmsofthedabigatranstudyshowednoninferiorityto
enoxaparin,withsimilarbleedingratesandwithmostmajorbleedingeventsbeingatthesurgicalsite.
TheREMOBILIZEtrialwascarriedoutinpatientsundergoingtotalkneereplacementsurgery.Inthisstudy,dabigatran
etexilate150mg/dayor220mg/daystartingwithadoseofeither75or110mg6to12hourspostoperatively,
respectivelyinthetwogroups,wascomparedwithenoxaparin30mgtwicedaily,starting12to24hours
postoperatively[180].Venographywasperformedatday12to15.Dabigatranfailedtomeetthepredefinedcriteriafor
noninferiorityagainstenoxaparinintermsofthecompositeendpoint.RatesformajorVTEordeathweresimilarand
majorbleedingeventswerecomparable.Aswithfondaparinuxandrivaroxaban,dabigatranwasnotaseffective
againsttheNorthAmericanregimenofenoxaparin(ie,30mgtwicedaily)asitwasagainstthedosingfavoredin
Europe(ie,40mgoncedaily).
Inallthreestudieswithdabigatrantherewasnosignificantelevationofliverenzymesorinthromboticeventsfollowing
thetreatmentperiod[178180].Basedonevidencefromthesetrials,dabigatranhasbeenapprovedforuseinanumber
ofcountriesinEurope,theUnitedStates,andCanada[181,182].

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ApixabanApixabanisaspecificinhibitorofactivatedfactorXwithexcellentoralbioavailabilityandahalflifeof
approximatelyeighthours.Itisprimarilymetabolizedbytheliver.Itsuseisnotrecommendedinthosewitha
creatinineclearance<15mL/minuteorinthosewithseverehepaticimpairment.(See"Directoralanticoagulants:
Dosingandadverseeffects",sectionon'Apixaban'.)
Inadoubleblindrandomizedstudycomparingapixabantoenoxaparinforthromboprophylaxisafterkneereplacement,
apixabandidnotmeettheprespecifiedcriteriafornoninferiority,butitsusewasassociatedwithlowerratesof
clinicallyrelevantbleedingandithadasimilaradverseeventprofiletoenoxaparin[183].OtherphaseIIandIIItrials
haveshownthatapixabancomparedfavorablytobothenoxaparinandwarfarinasVTEprophylaxisintotalknee
replacementsurgery[184186]andthatthromboprophylaxiswithapixaban,ascomparedwithenoxaparin,was
associatedwithsignificantlylowerratesofvenousthromboembolismwithoutincreasedbleedinginpatientsundergoing
totalhipreplacement[187].Dosereductionisnotrequiredifthecreatinineclearanceis30mL/min[188].
Arandomized,doserangingstudycomparedthreedifferentschedulesofapixaban(oraldailydosesof5mgtwice
daily,10mgtwicedaily,or20mgoncedaily)orLMWheparinfollowedbyavitaminKantagonist(VKA),allgivenfora
totalof84to91days,in520patientswithsymptomaticDVT.Resultsincluded[189]:
Theprimaryefficacyendpoint,acompositeofsymptomaticrecurrentVTEandasymptomaticdeteriorationof
bilateralcompressionultrasoundorperfusionlungscanobtainedattheendoftreatment,occurredin4.7and4.2
percentofthosetreatedwithapixabanandLMWheparin/VKA,respectively.
Theprimarysafetyendpoint,acompositeofmajorandclinicallyrelevant,nonmajorbleedingwasnotedin7.3
and7.9percentofthosetreatedwithapixabanandLMWheparin/VKA,respectively.
Therewasnoevidenceforadoseresponserelationshipwithapixabanforeithertheefficacyorsafetyendpoints.
Routineliverfunctiontestingrevealednoevidenceoflivertoxicity.
EdoxabanDataregardingtheuseofedoxaban,afactorXainhibitor,forthepreventionofVTEcomefromtwo
randomizedtrialsinJapanesepatientsundergoingtotalkneereplacementortotalhipreplacement.Thesetrials
(STARSE3andSTARSJ5)comparededoxabanwiththelowmolecularweightheparinenoxaparin[190].Apooled
analysisoftheresultsshowedthatwhencomparedwithenoxaparin,edoxabanwasassociatedwithalowerincidence
ofDVTandPE(5.1versus10.7percent)andasimilarsafetyprofile.(See"Directoralanticoagulants:Dosingand
adverseeffects",sectionon'Edoxaban'.)
ComparisonwithLMWheparinNumerousrandomizedtrialsandmetaanalyseshavecomparedtheefficacy
andsafetyoffactorXaanddirectthrombininhibitorstoconventionalVTEprophylaxisinpatientsfollowingtotalhipand
kneereplacement[124,126,127,168,191195].Themostcommonlystudiedagentsarethedirectthrombininhibitor,
dabigatran,andtheorallyactivefactorXainhibitorsrivaroxaban,apixaban,andedoxaban.Theseagentshavebeen
comparedtoLMWheparin(enoxaparin,dalteparin).Theyhavenotbeencomparedwithwarfarin,aspirin,orUFH.(See
"Directoralanticoagulants:Dosingandadverseeffects",sectionon'Dabigatran'and"Directoralanticoagulants:
Dosingandadverseeffects",sectionon'DirectfactorXainhibitors'.)
Whiledatafromrandomizedtrials,systematicreviewsandmetaanalysesreportfavorableeffectsonalloutcomes
(symptomaticDVT,nonfatalpulmonaryembolismandmortality),othersreportunchangedorimprovedratesof
symptomaticDVTonly[124,126,127,191194].Similarly,whilesomeanalysesreportnodifferenceinratesofbleeding
othersreportincreasedbleedingriskwiththeseagents.Conflictingresultsmaybeduetodifferencesamongthe
studiesintheagentused,dosing,timingofinitiation,durationofprophylaxis.Despiteconflictingdata,metaanalyses
suggestthat,onbalance,thebenefitsofdirectthrombininhibitorsandfactorXainhibitorsforthepreventionofVTEare
marginalandmaybeoffsetbyanincreasedriskofbleeding[127,194]:
One2012metaanalysisof22randomizedtrials(32,159patients)comparedthefactorXainhibitors(rivaroxaban,
apixaban,edoxaban)withLMWheparininadultsforVTEpreventionfollowinghiporkneereplacement[127].The
efficacyandsafetyofthedirectthrombininhibitorwasnotexaminedinthisanalysis.FactorXainhibitorswere
associatedwithareducedriskofsymptomaticDVT(4fewereventsper1000)withoutaneffectonnonfatal
pulmonaryembolismordeath.However,highdosesoffactorXainhibitors,butnotlowerdoses,increasedthe
riskofbleedingmorethantheLMWheparins(2morebleedingeventsper1000).Majorlimitationsofthisanalysis
werethatmanyincludedstudiesreportedbleedingasacompositeoutcomeandtheoutcomesweremissingin3
to41percentofpatients.Inaddition,theenoxaparindosinginmostoftheincludedstudieswasthelowerdoseof
40mgdaily,whereasinNorthAmericatheusualdoseofenoxaparinis30mgtwicedaily.Thus,useofa40mg
doseasacomparatormayfavorefficacywhileincreasebleedingeventsinthisanalysis.
AdditionalsystematicreviewsandmetaanalysesreportnodifferencebetweenLMWheparinandthedirect
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thrombininhibitor,dabigatran,intheratesofVTEprevention(relativerisk[RR]0.71,95%CI0.232.12)or
bleeding(RR1.12,95%CI0.941.35)[192,194].Inaddition,indirectcomparisonofthenewerorallyactiveagents
witheachothersuggestedthatrivaroxabanwasmoreefficaciousatpreventingsymptomaticDVT(RR0.50,95%
CI0.370.68)thandabigatranorapixabanbutwasassociatedwithexcessbleedingrisk(RR1.1495%CI0.80
1.64)[193,194].
Additionaltrialswillberequiredtoestablishtheoptimalagent,dosing,overallrelativesafety,andefficacyofthesenew
anticoagulantscomparedtoconventionalVTEprophylaxis.
AspirinWhileevidencefavorsaspirinforthepreventionofthromboticeventsinatheroscleroticdisease,itsefficacy
forthepreventionofVTEinmedicalandsurgicalpatientsisunclear.(See"Preventionofvenousthromboembolic
diseaseinacutelyillhospitalizedmedicaladults",sectionon'Aspirin'.)
Anoldermetaanalysissuggestedthat,comparedwithplacebo,aspirinreducedtheincidenceofVTEbyapproximately
20percent[196].However,otherstudiessuggestthatitislessefficaciouswhencomparedwithLMWheparin[197
200].Renewedinterestinaspirin,asaprophylacticagentinatriskpatientsledtoamulticenterrandomized,controlled
trialofaspirinin778surgicalpatientsaftertotalhipreplacement(THR)[108].Allpatientsreceived10daysofLMW
heparinpriortorandomization.ComparedtoLMWheparin,aspirinwasassociatedwithalowerrateofVTEthatdidnot
reachstatisticalsignificanceforsuperiority(0.3versus1.3percent).Thistrialwasstoppedearlyduetoslow
enrollmentandeventnumbersweresmallwhichmayexplainwhyafourfolddifferenceineventratesbetweenthe
groupswasnotreportedassuperior.
The2012ACCPGuidelinesincludedaspirinamongthelistofthromboprophylacticagentsthatcanbeconsideredfor
useinpatientsundergoingtotalhiportotalkneearthroplastyorhipfracturesurgery[201].However,itsusewasnot
unanimouslysupported.Wealsosuggestthatitcanbeconsidered,butisnotthepreferredagent,forextendedVTE
prophylaxisinthispopulationofsurgicalpatients.
MECHANICALMETHODSOFTHROMBOPROPHYLAXISMechanicalmethodsofthromboprophylaxisthathave
beenusedinsurgicalpatientsincludeintermittentpneumaticcompression(IPC),graduatedcompressionstockings
(GCS),andthevenousfootpump(VFP).
MechanicalmethodsforthepreventionofVTEareprimarilyindicatedinsurgicalpatientsathighriskofbleeding(eg,
followingneurosurgery,patientswithintracranialhemorrhage)andinwhomthereisacontraindicationtoanticoagulants
(eg,bleedingpepticulcer)[68].AmongthesedevicesIPCistypicallypreferred[68,120,202,203].Devicesaretypically
placedonthepatientjustpriortothestartofsurgeryandusedcontinuouslyuntilhospitaldischarge.Whenusedinany
ofthesecircumstances,considerationshouldbegiventotheadditionaluseofapharmacologicagent,suchasLMW
heparin,assoonasthebleedingriskbecomesacceptablylow(eg,48to72hoursfollowingneurosurgery)orwhenthe
bleedinglesionorbleedingriskhasbeenreversed[68].
IntermittentpneumaticcompressionIntermittentpneumaticcompression(IPC)preventsvenousthrombosisby
enhancingbloodflowinthedeepveinsofthelegs,therebypreventingvenousstasis[204].IPCalsoreduces
plasminogenactivatorinhibitor1(PAI1),therebyincreasingendogenousfibrinolyticactivity[205].(See"Vascular
endothelialfunctionandfundamentalmechanismsoffibrinolysis(thrombolysis)",sectionon'Plasminogenactivator
inhibitor1'and"Thromboticandhemorrhagicdisordersduetoabnormalfibrinolysis",sectionon'Plasminogenactivator
inhibitor1'.)
IPCisanalternativeforVTEpreventioninpatientswithahighriskofbleedingorinwhomanticoagulationis
contraindicated(eg,activeorintracranialhemorrhage).DatasupportingtheuseofIPCforthepreventionofVTEin
surgicalpatientsislimited.However,ofthemechanicaldevices(IPC,GCS,VFP),efficacyappearsbestwithIPCuse
[68,120,202,203,206].MetaanalysesofsmallrandomizedtrialsagreethatIPCuseissuperiortonoprophylaxisand
graduatedcompressionstockings,andmayofferadditivebenefittosurgicalpatientsonLMWheparin
[68,120,203,206,207].Thelargestmetaanalysis,whichincludeddataon16,164patientsenrolledin70trials,reported
thatIPCwasmoreeffectivethannoprophylaxisinreducingDVT(7.3versus16.7percentrelativerisk[RR]0.43
95%CI0.360.52)andPE(1.2versus2.8percent,RR0.4895%CI0.330.69)withoutanyeffectonmortality[207].
Onfurtheranalysis,althoughtheadditionofpharmacologicprophylaxistoIPCfurtherreducedtheriskofDVT(RR
0.5495%CI0.320.91),ithadnoeffectontheincidenceofPE.
IPCdevicesmayberemovedwhilethepatientisambulating,butshouldbeputbackonwhenthepatientreturnstoa
seatedorsupineposition.Attentionmustbepaidtooptimalcompliance,aswellasproperfitoftheIPCdevice.
However,reflectiveofpractice,oneobservationalstudyreportedfrequenterrorsinIPCapplication.Thissuggeststhat
frequentinterferencewiththedeviceiscommonandmaypotentiallyinterferewithefficacy[208].
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IPCiscontraindicatedinpatientswithevidenceoflegischemiaduetoperipheralvasculardisease.Althoughthereare
nodataavailableonskincomplicationsofIPCuse,skinbreakdownisaknowncomplication,especiallyinthefrail,
olderadultpopulation.Inaddition,practicalconsiderationsforamputeesorpatientswithburnsorextensiveskin
lesions(eg,StevensJohnsonssyndrome)maylimititsuse.Inthiscontext,althoughonedevicecanbeappliedtoany
extremity,itsefficacyinthepreventionofVTEisnotassuredandlikelylimited.Thereisalsoahypotheticalconcern
thatpatientswhohavebeenimmobilizedforaperiodof72hourswithoutanyformofprophylaxismaybeatriskof
dislodgingrecentlyformedvenousclotinthelowerextremities.Thevalueofclinicalexaminationorultrasoundin
determiningriskofclotdislodgementfollowingtheapplicationofIPCinthissettingisunknown.
OptimaltimingofIPCinsurgicalpatientsispoorlystudied.However,onestudysuggestedthatIPCshouldbestarted
assoonaspossible,preferablyintheoperatingroomorrecoveryroomandcontinuedwithfewinterruptionsuntil
discharge[209].Inastudyof957patientswithnohistoryofpriorVTEwhohadlaparoscopicRouxenYgastric
bypass,calflengthpneumaticcompressiondeviceswereplacedbeforeanesthesiainductionandmandatory
ambulationwasbegunonthedayofoperationwithouttheuseofpharmacologicanticoagulation[209].Theincidenceof
symptomaticpostoperativeVTEandbleedingcomplicationswerelowat0.42and0.73percent,respectively.
GraduatedcompressionstockingsThereisapaucityofhighqualityrandomizedtrialsthathavestudiedthe
efficacyofgraduatedcompressionstockings(GCS)inthesurgicalpopulation[203,210214].GCSaloneareeffective
atpreventingDVTbutmaybelesseffectivethanpharmacologicagents.However,GCSwhencombinedwithother
prophylacticmethodsappearstoimproveratesofDVTprevention.
Asexamples:
Onemetaanalysisof18randomizedtrialsinsurgicalpatientsreportedthattheuseofGCSalonewasmore
effectivethannoprophylaxisinthepreventionofDVT(26versus13percentoddsratio0.3595%CI0.260.47)
[212].
Inanothermetaanalysisofeightstudies,theincidenceofproximalDVTandPEwaslowerinpatientstreated
withGCScomparedwithpatientswithoutGCS(1versus5percent,2versus5percent,respectively)[214].
However,additionofasecondmethodofprophylaxisinsomeoftheincludedtrialsmayhavebiasedthe
favorableoutcomeassociatedwithGCSinthisanalysis.
Inonerandomizedtrialof1761patientsundergoingkneearthroplasty,alowerrateofDVTandmortalitywas
reportedinthosewhoweretreatedforsevendayswithLMWheparincomparedwithGCSalone(0.9versus3.2
percent)[210].However,manyoftheeventspreventedbyLMWheparinwereepisodesofasymptomaticdistal
DVT.
Anothermetaanalysisof25randomizedtrialsreportedthat,comparedtoeithermodalityalone,combiningGCS
withpharmacologicagentshalvedtherateofpostoperativeDVT(riskratio0.5195%CI0.360.73)whiletherisk
ofbleedingalmostdoubled(RR174,95%CI1.292.34)[213].Similarly,inanothermetaanalysis,ratesofDVT
preventionweregreatestinthosetreatedwithcompressionstockingsplusanyotherprophylacticmethod
comparedwithcompressionstockingsalone(4versus13percent)[212].
InferiorvenacavafiltersIngeneral,inferiorvenacavafiltersshouldbeavoidedasprimaryprophylaxisagainst
postoperativeDVT[215].TheindicationsforfilterplacementasatherapyforDVTarediscussedseparately.(See
"Placementofvenacavafiltersandtheircomplications"and"Overviewofthetreatmentoflowerextremitydeepvein
thrombosis(DVT)",sectionon'Inferiorvenacavafilter'.)
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,TheBasicsand
BeyondtheBasics.TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6thgradereading
level,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.Thesearticlesare
bestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.BeyondtheBasicspatient
educationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewrittenatthe10thto12thgrade
readinglevelandarebestforpatientswhowantindepthinformationandarecomfortablewithsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthesetopics
toyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingonpatientinfo
andthekeyword(s)ofinterest.)
BeyondtheBasicstopics(see"Patientinformation:Deepveinthrombosis(DVT)(BeyondtheBasics)"and
"Patientinformation:Warfarin(Coumadin)(BeyondtheBasics)")
SUMMARYANDRECOMMENDATIONS
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MedicalcenterpoliciesEveryhospitalshoulddevelopaformalactivestrategyforthepreventionofVTEin
medicalandsurgicalpatients.Thisshouldbeintheformofawritteninstitutionwidethromboprophylaxispolicy
endorsedbydepartmentheadsandmedicaladvisoryboards.Strategiesshouldbedevelopedtoincreasecompliance
withthromboprophylaxisrecommendations,includingtheuseofcomputerizedordersetsandprompts,preprinted
orders,andperiodicaudit,includingfollowupwithfeedback[164].(See'Problemoverview'above.)
Thearticle"PreventionofVenousThromboembolism:AmericanCollegeofChestPhysiciansEvidencebasedClinical
PracticeGuidelines(8thEdition)"isanextensivelyreferencedguidelineforthepreventionofVTE,whichmaybe
usefulinformulatingthesepolicies[164].TheirgradingsystemisidenticaltothatusedinUpToDate,andincludesboth
thestrengthoftherecommendationaswellasthequalityoftheavailableevidence.Theconceptofvaluesand
preferenceshasalsobeenincorporatedintoanumberoftheserecommendations.(See'Valuesandpreferences'
above.)
GroupversusindividualrecommendationsNumerousattemptshavebeenmadetodevelopriskassessment
modelsforVTEinindividualpatients[43,44,47,49,5255].Atthistime,noneoftheriskstratificationmodelshasbeen
validatedinprospectivetrials,althoughthissubjectisunderactivestudy[60,164].
SinceclinicaltrialsforthepreventionofVTEhavebeensuccessfullycarriedoutonlyinspecificsurgicalgroups,the
followingrecommendationsarethereforegroupspecific,withimportantcaveats[38]:
Inpatientswithadditionalriskfactors(eg,previousVTE,advancedageparticularly>75,activecancerora
historyofcancer,amoreextensivethanusualsurgicalprocedure)considerationshouldbegiventomore
aggressiveprophylaxisintheformofincreasedintensityordurationofapharmacologicagent,ortheadditionofa
mechanicaldevicesuchasIPC[164].
Inpatientsfromspecificethnicgroupsinwhichtheincidenceofpostsurgicalvenousthromboembolismislow
(eg,Asianpopulations),considerationmaybegiventolessaggressiveprophylaxis[216].
AssignmentofsurgicalriskgroupsTheriskofpostoperativeVTEdependsuponthesurgicalprocedure(eg,
degreeofinvasiveness,typeanddurationofanaesthesia,requirementforimmobilization),aswellaspatientrelated
variables(eg,increasingage,priorVTE,presenceofmalignancyorobesity,presenceofaninheritedoracquired
hypercoagulablestate).Patientshavebeengenerallydividedintoverylow,low,moderate,andhighriskcategories.
(See'Surgicalriskgroups'above.)
GroupspecificrecommendationsGroupspecificrecommendationsarebaseduponthesurgicalriskgroup
classificationnotedabove,basedinpartontheuseofthemodifiedCapriniriskassessmentmodel(table2).
ContraindicationtoanticoagulationForsurgicalpatientswithriskfactorsforVTEforwhomthereisa
contraindicationtoanticoagulantthromboprophylaxis,werecommendtheoptimaluseofmechanicalmethodsof
thromboprophylaxis(Grade1B).(See'Mechanicalmethodsofthromboprophylaxis'above.)
Considerationshouldbegiventotheuseofapharmacologicagent(eg,LMWheparin)assoonasthebleedingrisk
becomesacceptablyloworwhenthebleedinglesionorbleedingriskhasbeenreversed.
VerylowriskgeneralandabdominalpelvicsurgerypatientsForverylowriskgeneralandabdominalpelvic
surgery(Capriniscorezero)werecommendagainsttheuseofspecificthromboprophylaxisotherthanearlyand
frequentambulation(Grade1B).(See'Verylowriskpatients'above.)
LowriskgeneralandabdominalpelvicsurgerypatientsForlowriskgeneralandabdominalpelvicsurgery
(Capriniscore1to2)wesuggesttheuseofmechanicalprophylaxis,preferablywithintermittentpneumatic
compression,overnoprophylaxisorprophylacticanticoagulation(Grade2C).(See'Lowriskpatients'above.)
ModerateriskgeneralandabdominalpelvicsurgerypatientsFormoderateriskgeneralandabdominalpelvic
surgery(Capriniscore3to4)werecommendtheuseofprophylacticanticoagulationovernoprophylaxis(Grade1B).
(See'Moderateriskpatients'above.)
ReasonablechoicesincludeLMWheparin,lowdoseunfractionatedheparin,orfondaparinuxatdosesrecommendedby
themanufacturer.
HighriskgeneralandabdominalpelvicsurgerypatientsForhighriskgeneralandabdominalpelvicsurgery
(Capriniscore5ormore)werecommendtheuseofprophylacticanticoagulationoverothermethods(Grade1B).(See
'Highriskpatients'above.)
ReasonablechoicesincludeLMWheparin,lowdoseunfractionatedheparinthreetimesdaily,orfondaparinux.
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Additionalguidanceinpatientsundergoinggynecologicsurgerycanbefoundelsewhere.(See"Overviewof
preoperativeevaluationandpreparationforgynecologicsurgery",sectionon'Thromboprophylaxis'.)
BecausesurgicalpatientswithmultipleVTEriskfactorsarethoughttobeatthehighestriskforVTE,wesuggestthat
apharmacologicmethodbecombinedwithoptimaluseofamechanicalmethod(Grade2C).(See'Surgicalrisk
groups'above.)
Specialgroups
Forobesepatients,includingthoseundergoinginpatientbariatricsurgery,pharmacologicprophylaxiswithLMW
heparinorlowdoseunfractionatedheparinispreferred.(See"Bariatricsurgery:Postoperativeandlongterm
managementoftheuncomplicatedpatient",sectionon'Venousthromboembolism'and"Bariatricsurgery:
Intensivecareunitmanagementofthecomplicatedpostoperativepatient",sectionon'Anticoagulantdosing'.)
Forpatientsadmittedtoacriticalcareunit,burnpatientswithadditionalriskfactors,acutespinalcordinjury,or
thosewithmajortrauma,werecommendroutineassessmentforVTEriskandroutinethromboprophylaxisin
most(Grade1A).
Forpatientsundergoingelectivetotalhiportotalkneereplacement,werecommendtheroutineuseof
pharmacologicprophylaxis(Grade1A).Reasonablechoicesinclude:LMWheparinatausualhighriskdose,
fondaparinux,avitaminKantagonist(targetINR2.5,range:2.0to3.0),dabigatran,orrivaroxaban.Allhavebeen
approvedforthisindication.
Forpatientsundergoingtotalkneereplacement,theoptimaluseofintermittentpneumaticcompression(IPC)is
analternativeoptiontoanticoagulantprophylaxisforpatientswithahighbleedingrisk,orcanbeemployedin
combinationwithotherthromboprophylacticoptions.(See'Intermittentpneumaticcompression'above.)
Lengthoftreatment
Formoderateriskpatientsundergoingmajorgeneralandabdominalpelvicsurgicalprocedures,werecommend
thatthromboprophylaxiscontinueuntilhospitaldischarge,ratherthanforashorterorlongerperiod(Grade1A).
Forselectedhighriskgeneralandabdominalpelvicsurgerypatients,includingthosewhohaveundergonemajor
cancersurgeryorhavepreviouslyhadVTE,wesuggestthatcontinuingthromboprophylaxisafterhospitalization
withLMWheparinforupto28daysbeconsidered(Grade2A).(See'Extendedprophylaxis'above.)
Forpatientsundergoingtotalhipreplacementorhipfracturesurgery,werecommendthatthromboprophylaxisbe
extendedbeyond10daysandupto35daysaftersurgery(Grade1A).Forpatientsundergoingtotalknee
replacement,wesuggestthatthromboprophylaxisbeextendedbeyond10daysandupto35daysaftersurgery
(Grade2B).OptionsincludeLMWheparin,fondaparinux,oravitaminKantagonist.(See"Medicalconsultation
forpatientswithhipfracture",sectionon'Thromboembolicprophylaxis'.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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Topic1339Version79.0

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GRAPHICS
HospitalQualityAlliance/CentersforMedicare&MedicaidServices
(CMS)SurgicalCareImprovementqualitymeasuresforperioperative
VTEprevention*
Recommendedprophylaxisoptions

Surgerytype
Intracranialneurosurgery

Anyofthefollowing:
Intermittentpneumaticcompressiondevices(IPC)withorwithout
graduatedcompressionstockings(GCS)
Lowdoseunfractionatedheparin(LDUH)
Lowmolecularweightheparin(LMWH)
LDUHorLMWH combinedwithIPCorGCS

Generalsurgery

Anyofthefollowing:
Lowdoseunfractionatedheparin(LDUH)
Lowmolecularweightheparin(LMWH)
FactorXaInhibitor(fondaparinux)
LDUHorLMWHorFactorXaInhibitorcombinedwithintermittent
pneumaticcompressiondevices(IPC)orgraduated
compressionstockings(GCS)

Generalsurgerywith
contraindicationsto
pharmacologicalprophylaxis
Gynecologicsurgery

Anyofthefollowing:
Graduatedcompressionstockings(GCS)
Intermittentpneumaticcompressiondevices(IPC)

Anyofthefollowing:
Lowdoseunfractionatedheparin(LDUH)
Lowmolecularweightheparin(LMWH)
FactorXaInhibitor(fondaparinux)
Intermittentpneumaticcompressiondevices(IPC)
LDUHorLMWHorFactorXaInhibitorcombinedwithIPCor
graduatedcompressionstockings(GCS)

Urologicsurgery

Anyofthefollowing:
Lowdoseunfractionatedheparin(LDUH)
Lowmolecularweightheparin(LMWH)
FactorXaInhibitor(fondaparinux)
Intermittentpneumaticcompressiondevices(IPC)
Graduatedcompressionstockings(GCS)
LDUHorLMWHorFactorXaInhibitorcombinedwithIPCorGCS

Electivetotalhipreplacement

Anyofthefollowingstartedwithin24hoursofsurgery:
Lowmolecularweightheparin(LMWH)
FactorXaInhibitor(fondaparinux)
Warfarin

Excludedpopulations:
Patientslessthan18yearsofage
Patientswhohavealengthofstay>120days

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Burnpatients
Patientswithproceduresperformedentirelybylaparoscope
Patientsenrolledinclinicaltrials
Patientswhoareonwarfarinpriortoadmission
PatientswhoseICD9CMprincipalprocedureoccurredpriortothedateofadmission
Patientswhosetotalsurgerytimeislessthanorequalto60minutes
Patientswhostayedlessthanorequaltothreecalendardayspostoperatively
Patientswithcontraindicationstobothmechanicalandpharmacologicalprophylaxis
*Takenfrom:SpecificationsManualforNationalHospitalInpatientQualityMeasures.Availableat:
www.qualitynet.org.
Patientswhoreceiveneuraxialanesthesiaorhaveadocumentedcontraindicationtopharmacological
prophylaxismaypasstheperformancemeasureifeitherappropriatepharmacologicalormechanical
prophylaxisisordered.
Currentguidelinesrecommendpostoperativelowmolecularweightheparinforintracranialneurosurgery.
Graphic50947Version5.0

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ModifiedCapriniriskassessmentmodelforVTEingeneralsurgical
patients
Riskscore
1point

2points

3points

5points

Age41to60years

Age61to74years

Age75years

Stroke(<1month)

Minorsurgery

Arthroscopicsurgery

HistoryofVTE

Electivearthroplasty

BMI>25kg/m 2

Majoropensurgery

FamilyhistoryofVTE

Hip,pelvis,orleg

(>45minutes)
Swollenlegs

fracture

Laparoscopicsurgery

FactorVLeiden

(>45minutes)

Acutespinalcordinjury
(<1month)

Varicoseveins

Malignancy

Prothrombin20210A

Pregnancyor
postpartum

Confinedtobed(>72
hours)

Lupusanticoagulant

Historyofunexplained

Immobilizingplaster

Anticardiolipin

orrecurrent

cast

antibodies

Centralvenousaccess

Elevatedserum

spontaneousabortion
Oralcontraceptivesor
hormonereplacement
Sepsis(<1month)

homocysteine

Heparininduced

thrombocytopenia
Seriouslungdisease,
includingpneumonia

Othercongenitalor
acquiredthrombophilia

(<1month)
Abnormalpulmonary
function
Acutemyocardial
infarction
Congestiveheartfailure
(<1month)
Historyofinflammatory
boweldisease
Medicalpatientatbed
rest

Interpretation
EstimatedVTEriskin
theabsenceof
Surgicalrisk
category*

Score

pharmacologicor
mechanical
prophylaxis
(percent)

Verylow(seetextfor

<0.5

Low

1to2

1.5

Moderate

3to4

3.0

High

6.0

definition)

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VTE:venousthromboembolismBMI:bodymassindex.
*Thistableisapplicableonlytogeneral,abdominalpelvic,bariatric,vascular,andplasticandreconstructive
surgery.Seetextforothertypesofsurgery(eg,cancersurgery).
From:GouldMK,GarciaDA,WrenSM,etal.PreventionofVTEinnonorthopedicsurgicalpatients:
antithrombotictherapyandpreventionofthrombosis,9thed:AmericanCollegeofChestPhysiciansevidence
basedclinicalpracticalguidelines.Chest2012141:e227S.Copyright2012.Reproducedwithpermission
fromtheAmericanCollegeofChestPhysicians.
Graphic83739Version13.0

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ContributorDisclosures
MenakaPai,MD,FRCPCSpeaker'sBureau:Bayer[VTE(rivaroxaban)].Consultant/AdvisoryBoards:Bayer[VTE
(rivaroxaban)]BMSPfizer[VTE(apixaban)]Sanofi[VTE(enoxaparin)].JamesDDouketis,MD,FRCPC,FACP,
FCCPConsultant/AdvisoryBoards:Actelion[adjudicationcommittee(noproduct)]AGENBiomedical[diagnostic
imaging(noproduct)]AspenPharmaceuticals[venousthromboembolicdisease(nadroparin)]AstraZeneca[acute
coronarysyndrome(ticagrelor)]Biotie[chronicneurologicaldisease(noproduct)]Boehringer[venousthromboembolic
diseaseandatrialfibrillation(dabigatran)]Bayer[venousthromboembolicdiseaseandatrialfibrillation(rivaroxaban)]
BMS[venousthromboembolicdiseaseandatrialfibrillation(apixaban)]Pfizer[venousthromboembolicdisease
(dalteparin)]Sanofi[venousthromboembolicdisease(enoxaparin)]LeoPharma[venousthromboembolicdisease
(tinzaparin)]TheMedicinesCo.[acutecoronarysyndrome(cangrelor)].LawrenceLKLeung,MDNothingtodisclose.
JessMandel,MDNothingtodisclose.GeraldineFinlay,MDNothingtodisclose.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressed
byvettingthroughamultilevelreviewprocess,andthroughrequirementsforreferencestobeprovidedtosupportthe
content.AppropriatelyreferencedcontentisrequiredofallauthorsandmustconformtoUpToDatestandardsof
evidence.
Conflictofinterestpolicy

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