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.