EvidenceBasedManagementof

AnticoagulantTherapy

AntithromboticTherapyandPrevention
ofThrombosis,9thed:American
CollegeofChestPhysiciansEvidence
BasedClinicalPracticeGuidelines

Copyright:AmericanCollegeofChestPhysicians2012

Introduction
Thischapteraddressesthemanygeneralmanagement
questionsrelatedtoanticoagulants:
Includesinitiation,maintenance,dosing,drug
interactions,bleeding,organizationofcare
Managementinpregnancyandforchildrenis
coveredinotherchapters
Systematicreviewsrevealedsufficientbutusuallylow
qualityevidencetoprovidesuggestedguidanceforonly
23questions
Onlytwoquestions(INRtherapeuticrange23;
avoidanceofroutinepharmacogenetictestingto
guideVKAdosing)hadsufficientevidenceto
supportastrongrecommendation.

LoadingDoseforInitiationofVitaminKAntagonist(VKA)Therapy

Forpatientssufficientlyhealthytobetreatedasoutpatients,we
suggestinitiatingVKAtherapywithwarfarin10mgdailyforthe
first2daysfollowedbydosingbasedoninternationalnormalized
ratio(INR)measurementsratherthanstartingwiththeestimated
maintenancedose(Grade2C).

InitialDoseSelectionandPharmacogeneticTesting

ForpatientsinitiatingVKAtherapy,werecommendagainstthe
routineuseofpharmacogenetictestingforguidingdosesofVKA
(Grade1B).

InitiationOverlapforHeparinandVKA
ForpatientswithacuteVTE,wesuggestthatVKAtherapybe
startedonday1or2oflowmolecularweightheparin(LMWH)or
lowdoseunfractionatedheparin(UFH)therapyratherthanwaiting
forseveraldaystostart(Grade2C).

MonitoringFrequencyforVKAs
ForpatientstakingVKAtherapywithconsistentlystableINRs,we
suggestanINRtestingfrequencyofupto12weeksratherthan
every4weeks(Grade2B).

ManagementoftheSingleOutofRangeINR

ForpatientstakingVKAswithpreviouslystabletherapeuticINRs
whopresentwithasingleoutofrangeINRof0.5belowor
abovetherapeutic,wesuggestcontinuingthecurrentdoseand
testingtheINRwithin1to2weeks(Grade2C).

BridgingforLowINRs
ForpatientswithstabletherapeuticINRspresentingwithasingle
subtherapeuticINRvalue,wesuggestagainstroutinely
administeringbridgingwithheparin(Grade2C).

VitaminKSupplementation
ForpatientstakingVKAs,wesuggestagainstroutineuseof
vitaminKsupplementation(Grade2C).

AnticoagulationManagementServicesforVKAs

(BestPracticesStatement)Wesuggestthathealthcareproviders
whomanageoralanticoagulationtherapyshoulddosoina
systematicandcoordinatedfashion,incorporatingpatient
education,systematicINRtesting,tracking,followup,andgood
patientcommunicationofresultsanddosingdecisions.

PatientSelfTestingandSelfManagement
ForpatientstreatedwithVKAswhoaremotivatedandcan
demonstratecompetencyinselfmanagementstrategies,including
theselftestingequipment,wesuggestpatientselfmanagement
ratherthanusualoutpatientINRmonitoring(Grade2B).Forall
otherpatients,wesuggestmonitoringthatincludesthesafeguards
inourbestpracticestatement3.5.

DosingDecisionSupport
FordosingdecisionsduringmaintenanceVKAtherapy,wesuggest
usingvalidateddecisionsupporttools(papernomogramsor
computerizeddosingprograms)ratherthannodecisionsupport
(Grade2C).
Remarks:Inexperiencedprescribersmaybemorelikelytoimprove
prescribingwithuseofdecisionsupporttoolsthanexperienced
prescribers.

VKADrugInteractionstoAvoid
ForpatientstakingVKAs,wesuggestavoidingconcomitant
treatmentwithnonsteroidalantiinflammatorydrugs,including
cyclooxygenase2selectivenonsteroidalantiinflammatorydrugs,
andcertainantibiotics(seeTable8inmainarticle)(Grade2C).
ForpatientstakingVKAs,wesuggestavoidingconcomitant
treatmentwithantiplateletagentsexceptinsituationswherebenefit
isknownorishighlylikelytobegreaterthanharmfrombleeding,
suchaspatientswithmechanicalvalves,patientswithacute
coronarysyndrome,orpatientswithrecentcoronarystentsor
bypasssurgery(Grade2C).

OptimalTherapeuticINRRange
ForpatientstreatedwithVKAs,werecommendatherapeuticINR
rangeof2.0to3.0(targetINRof2.5)ratherthanalower(INR<2)
orhigher(INR3.05.0)range(Grade1B).

TherapeuticRangeforHighRiskGroups
Forpatientswithantiphospholipidsyndromewithpreviousarterial
orvenousthromboembolism,wesuggestVKAtherapytitratedtoa
moderateintensityINRrange(INR2.03.0)ratherthanhigher
intensity(INR3.04.5)(Grade2B).

DiscontinuationofTherapy
ForpatientseligibletodiscontinuetreatmentwithVKA,we
suggestabruptdiscontinuationratherthangradualtaperingofthe
dosetodiscontinuation(Grade2C).

UnfractionatedHeparin(UFH)DoseAdjustmentbyWeight

ForpatientsstartingIVUFH,wesuggestthattheinitialbolusand
theinitialrateofthecontinuousinfusionbeweightadjusted(bolus
80units/kgfollowedby18units/kgperhforVTE;bolus70
units/kgfollowedby15units/kgperhforcardiacorstroke
patients)oruseofafixeddose(bolus5,000unitsfollowedby
1,000units/h)ratherthanalternativeregimens(Grade2C).

DoseManagementofSubcutaneous(SC)UFH

ForoutpatientswithVTEtreatedwithSCUFH,wesuggest
weightadjusteddosing(firstdose333units/kg,then250units/kg)
withoutmonitoringratherthanfixedorweightadjusteddosing
withmonitoring(Grade2C).

TherapeuticDoseofLMWHinPatientsWithDecreasedRenalFunction

ForpatientsreceivingtherapeuticLMWHwhohavesevererenal
insufficiency(calculatedcreatinineclearance<30mL/min),we
suggestareductionofthedoseratherthanusingstandarddoses
(Grade2C).

FondaparinuxDoseManagementbyWeight

ForpatientswithVTEandbodyweightover100kg,wesuggest
thatthetreatmentdoseoffondaparinuxbeincreasedfromtheusual
7.5mgto10mgdailySC(Grade2C).

VitaminKforPatientsTakingVKAsWithHighINRsWithoutBleeding

(a)ForpatientstakingVKAswithINRsbetween4.5and10and
withnoevidenceofbleeding,wesuggestagainsttheroutineuseof
vitaminK(Grade2B).

(b)ForpatientstakingVKAswithINRs>10.0andwithno
evidenceofbleeding,wesuggestthatoralvitaminKbe
administered(Grade2C).

ClinicalPredictionRulesforBleedingWhileTakingVKA

ForpatientsinitiatingVKAtherapy,wesuggestagainsttheroutine
useofclinicalpredictionrulesforbleedingasthesolecriterionto
withholdVKAtherapy(Grade2C).

TreatmentofAnticoagulantRelatedBleeding

ForpatientswithVKAassociatedmajorbleeding,wesuggest
rapidreversalofanticoagulationwithfourfactorprothrombin
complexconcentrateratherthanwithplasma.(Grade2C).
WesuggesttheadditionaluseofvitaminK5to10mg
administeredbyslowIVinjectionratherthanreversalwith
coagulationfactorsalone(Grade2C).

EndorsingOrganizations
Thisguidelinehasreceivedtheendorsementofthe
followingorganizations:
AmericanAssociationforClinicalChemistry
AmericanCollegeofClinicalPharmacy
AmericanSocietyofHealthSystemPharmacists
AmericanSocietyofHematology
InternationalSocietyofThrombosisandHemostasis

AcknowledgementofSupport
TheACCPappreciatesthesupportofthefollowingorganizations
forsomepartoftheguidelinedevelopmentprocess:
BayerScheringPharmaAG
NationalHeart,Lung,andBloodInstitute(GrantNo.R13HL104758)
Witheducationalgrantsfrom

BristolMyersSquibbandPfizer,Inc.
CanyonPharmaceuticals,and
sanofiaventisU.S.
Althoughtheseorganizationssupportedsomeportionofthedevelopment
oftheguidelines,theydidnotparticipateinanymannerwiththescope,
panelselection,evidencereview,development,manuscriptwriting,
recommendationdraftingorgrading,voting,orreview.Supportersdidnot
seetheguidelinesuntiltheywerepublished.