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Transcript of ANTICOAGULANTS - Time of Care · PDF file1. All of the new oral anticoagulants are at least as...
ANTICOAGULANTS KennethAcha,MDUCRSchoolofMedicineFMResidencyProgram05/12/2016
1. Dr. William W. Wilson, FACC 2. Jeffrey I Weitz, MD, FRCP(C), FACP 3. Dr. Kyna Ngo, PharmD
Acknowledgments
1. History of oral anticoagulants 2. Anticoagulant types & Indications 3. Mechanism of Action 4. Switching between Anticoagulants 5. Perioperative Management of Anticoagulants 6. Monitoring and Reversal
Objectives
1. All of the new oral anticoagulants are at least as effective as warfarin and can be given without routine monitoring.
2. All DOACs reduce the risk of intracranial bleeding 3. New agents produce about a 10% reduction in
mortality. 4. You don’t need bridging with DOACs. 5. Most pts on warfarin don’t need bridging.
Take Home Points
History of oral Anticoagulation
Started with Warfarin ü Prior to 2009, warfarin was the only drug and has been in
clinical use since 1955 ü Reduces risk of stroke in AF by 66% ü Reduces risk of recurrent events, complications, and
death from PE and DVT by at least 80% ü Markedly reduces risk of valve thrombosis and emboli in
mechanical valve prostheses ü Perception of warfarin as “bad drug”
Pros of Warfarin
ü It works
ü It’s cheap, and ü It’s unaffected by renal function
Three good things:
Cons of Warfarin
ü Prolonged onset of effect ü Prolonged offset of effect ü Highly protein bound ü Highly affected by diet ü Highly affected by other medications ü Large individual variation in metabolism ü Need for frequent monitoring
It’s Difficult to Manage.
The Ideal Anticoagulant
ü WidetherapeuBcmarginü Infrequentoraldosingü Lackoffood/druginteracBonsü Noneedforlaboratorymonitoringü Readilyreversibleeffectü Affordability
Desired Properties
Why We Need a Replacement for Warfarin in AF
ü SlowonsetofacBonü UnpredictableandvariableanBcoagulanteffectü NumerousfoodanddruginteracBons
ü Highriskofintracranialbleedingü UndertreatmentofAFpaBents
ü SubopBmalanBcoagulantcontrolinpaBentstreatedwithwarfarin
Limitations of Warfarin
Worldwide Utilization of Oral Anticoagulation in AF: Results from a Global Registry
FDA approves DOACs ü 2010:Dabigatran(PRADAXA)forstrokeprevenBoninAFü 2011:Rivaroxaban(XARELTO)forstrokeprevenBoninAFü 2014:Apixaban(ELIQUIS)forVTE(DVT&PE)treatment
ü 2015:Edoxaban(Savaysa)forstrokeprevenBon
Direct Oral Anticoagulants (DOACs) ü Dabigatran(PRADAXA)–directFactorIIa(thrombin)inhibitor
ü Rivaroxaban(XARELTO)–directFactorXainhibitorü Apixaban(ELIQUIS)–directFactorXainhibitorü Edoxaban(Savaysa)–directFactorXainhibitor
Types of Anticoagulants
AnBcoagulants
Parenteral
HeparinLMWH(Enoxaparin,Dalteparin,etc)FondaparinuxParenteralDTIs(Bivalirudin,Argatroban,Desirudin)NoparenteraldirectfactorXainhibitors
Oral
WarfarinDabigatran(Pradaxa)Rivaroxaban(Xarelto)Apixaban(Eliquis)Edoxaban(Savaysa)
Mnemonic For Anticoagulants ü IIa : Dabigatran, Bivalirudin, ArgaTroban ü Xa : ApiXaban, RivaroXaban, FondaparinuX ü Both Factors (Pair): Heparins - UFH, LMWHs (Enoxparin,
Dalteparin, etc) ü Don’t forget Warfarin that is a vitamin K antagonist
Indications for Anticoagulants
Indications for Parenteral Anticoagulants
ü Preven&onofvenousthromboembolism(VTE)
ü Ini&altreatmentofarterialorvenousthrombosis
ü RevascularizaBonProceduresü Unstableangina,myocardialinfarcBon,coronarystenBng
ü Heparin-inducedthrombocytopenia(i.e.non-heparinparenteralanBcoagulants)
Advantages of LMWHs
ü Once-dailysubcutaneousadministraBon
ü NoneedforrouBnemonitoring
ü LowriskofHIT
Disadvantages of LMWHs
ü PotenBalforaccumulaBoninpaBentswithrenalimpairment
ü LackofananBdoteü RiskofcatheterthrombosisifusedasthesoleanBcoagulant
Indications for Oral Anticoagulants ü Preven&onofvenousthromboembolism(VTE)
ü TreatmentofVTE
ü AtrialfibrillaBontopreventembolicstroke
Advantages of DOACs ü AffectsonlyonecoagulaBonfactor(eitherXaorIIa)ü IndependentofanB-thrombinIIIunlikeheparinsü AcBveagainstfree(soluble)andclot-boundthrombinunlikeheparinswhichareonlyacBve
againstsolublefactsleadingtothepossibilityofthrombusextensionwhileonheparintxü Donotinduceimmune-mediatedthrombocytopeniaü LessIntracranialbleeding,eventhoughoverallrisksofbleedingaresimilartoVKAs.ü Noneedforlaboratorymonitoring.BothHeparinandWarfarinhavenarrowtherapeuBc
widowsandmorevariabledoseresponserelaBonshipthatdependsonavarietyoffactors,assuchneedfrequentmonitoring.
ü NotaffectedbydietorvitKintakeasmuchasWarfarin.ü LessinteracBonswithotherdrugs.
Advantages of New Oral Anticoagulants Over Warfarin
Feature
Warfarin
New DOAC
Onset
Slow Rapid
Dosing Variable Fixed
Food effect Yes No
Interactions Many Few
Monitoring Yes No
Offset Long Shorter
MOA of DOACs
Coagulation Cascade
SchemaBcrepresentaBonofthecoagulaBon.HK:high-molecular-weightkininogen;PK:prekallikrein;PL:phospholipid.From:Uptodate.com
Coagulation cascade: Anticoagulant effects
Mechanism of Action: Clinical Implications
ü Comparedtowarfarin,DOACsdonotinhibitproduc&onofclodngfactors.ü Theybindtothefactorsdirectly.E.g.DTIsbinddirectlytothrombinratherthanenhancingtheacBvityofanBthrombinasisdonebyheparin.
ü Thus,rapidonsetandoffsetofeffectü DOACsdonotinvolveVitaminKmetabolism.ü DOACSnotaffectedbyfood/vitaminKintakeü AnBcoagulanteffectofDOACsnotreversedbyvitaminK
Comparative Pharmacology
Characteristic
Rivaroxaban
Apixaban
Dabigatran
Target
Factor Xa
Factor Xa
Thrombin
Prodrug No No Yes Bioavailability 80% 60% 6%
Dosing o.d. (b.i.d) b.i.d b.i.d. (o.d.) Half life 7-11h 12h 12-17h Renal 33% (66%) 25% 80%
Monitoring No No No Interactions 3A4/P-gp 3A4/P-gp P-gp
Pharmacokinetics, Dosage Forms, Administration
Clinical Trials
Clinical Trials of DOACs: Atrial Fibrillation v RE-LY ------dabigatran v ROCKET AF -----rivaroxaban v ARISTOTLE -----apixaban Each of these trials randomly assigned 15,000 to 20,000 patients to warfarin versus another oral anticoagulant (dabigatran, rivaroxaban, or apixaban, respectively) RE-LY (Randomized Evaluation of Long-Term Anticoagulant Therapy), ROCKET AF (Rivaroxaban Once daily, oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation), and ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation)
RE-LYü Dabigatran 150 mg bid was superior to warfarin in preventing
embolic stroke ü Dabigatran 150 mg bid was equivalent to warfarin in bleeding
complications ü 110 mg bid dose was equivalent to warfarin in preventing
embolic stroke and was associated with less bleeding ü Both doses of dabigatran were associated with LESS
intracranial hemorrhage ü More GI bleeding with dabigatran
ROCKET-AF ü Sicker group of patients ü Rivaroxaban 20 mg daily was noninferior to warfarin in preventing
embolic stroke ü Rivaroxaban was associated with the same amount of overall
bleeding as warfarin ü Rivaroxaban was associated with LESS intracranial and fatal
hemorrhage ü Was associated with more GI bleeding
ARISTOTLE
ü Apixaban 5 mg bid was superior to warfarin in preventing embolic stroke
ü Apixaban was associated with less major hemorrhage than warfarin
ü Less intracranial hemorrhage ü NO greater incidence of GI bleeding ü Overall mortality lower compared to warfarin
HighlightsofClinicalTrialsinAFü All DOACs either as good or better than warfarin in preventing
embolic stroke in AF ü All DOACs associated with either the same or less bleeding than
warfarin in AF ü All DOACS associated with LESS intracranial hemorrhage
compared to warfarin ü DOACS associated with slightly less (10%) mortality compared to
warfarin
Phase3TrialsofDOACsvs.StandardofCareforAcuteVTETreatment
ConclusionsDOACs were noninferior to standard therapy (LMWH with transition to warfarin) in the treatment of acute DVT and PE and was associated with similar rates of major bleeding
Choosing Between Agents
WithLessHemorrhagicStroke,WhyNotSwitchEveryonetoNewOralAnBcoagulants?
Drug
NNT*
Dabigatran (150mg)
182
Rivaroxaban 333
Apixaban 238
*NNT: Number needed to treat to prevent one hemorrhagic stroke compared with warfarin
*NNT: Number needed to treat to prevent one hemorrhagic stroke compared with warfarin
How Do We Choose Amongst the Agent
Apixaban is not yet licensed for the AF indication
Characteristic
Drug choice
Rationale
CrCI30-50ml/min
Rivaroxaban or apixaban Less affected by renal impairment than dabigatran
Ischemic stroke on warfarin
Dabigatran Lower risk of ischemic stroke with dabigatran (150 mg)
Dyspepsia or upper CI complaints
Rivaroxaban or apixaban Dyspepsia with dabigatran in up to 10% of patients
Recent GI bleed
Apixaban More GI bleeding with dabigatran (150 mg) or rivaroxaban
Significant CAD
Rivaroxaban or apixaban
Small MI signal with dabigatran
Poor compliance with-twice daily dosing
Rivaroxaban Only agent given once-daily
When a Heparin or VKA is Preferable ü Prosthe?cheartvalves–DOACsarecontraindicated2/2greaterriskofvalvethrombosis,whichmay
befatal.
ü Pregnancy–DOACsarecontraindicatedduringpregnancy2/2lackofclinicalexperienceinthissedng;UseLMWheparin.
ü Renalimpairment(PoorCrCl)–HeparinorwarfarinmaybepreferabletoDOACsinptswithrenalimpairment.DOACSarerenallyexcretedtovariabledegrees.Thus,heparingenerallyisusedinhospitalizedptswithrenalinsufficiency.Foroutpts,warfarinordose-adjustedLMWHispreferredoveraDOACinthosewithreducedrenalfuncBon(eg,CrCl≤30mL/min)whorequirelong-termanBcoagulaBon.ExcepBonisEliquiswhichisFDAapprovedforuseinptswithrenalfailureincludingthoseondialysis.
ü Stableonthewarfarin.Ptswhoaredoingwellonwarfarinw/noissueshavenoadvantageinswitching.
When a Heparin or VKA is Preferable ü Frequentmisseddoses–Don’tuseDOAC’sinptsatriskfornoncompliance.1)Youcan’tmonitor.2)
MissingoneortwodosescanleavethepaBentinadequatelyanBcoagulated;incontrast,missingacoupleofdosesofwarfarinisunlikelytosubstanBallyincreasetheBmeoutsidethetherapeuBcrange.
ü GIdisease–GIbleeding,Severeliverdisease.AvoidDOACswithnoanBdoteinptswithincreasedriskofGIbleed.Ptswithseveredyspepsiamaynottoleratedabigatran.
ü Dosingconvenience–DabigatranandapixabanrequireBIDdosingvs.Warfarinthatisqd.
ü Cost–VKAaretypicallymuchcheaperthanDOACs.
Starting or Switching Between
Diff. Oral Agents
ApprovedDosingofWarfarinandDOACsforAFandVTE
bDOACsareindicatedonlyfornon-valvularAF.
Switching from VKA (Warfarin) to a DOAC
ü PeakonsetofacBonofnewagentsoccurswithin2to3hoursü D/ctheVKA,monitorPT/INRandiniBatetheDOACwhenINRis≤2.0ü RemembertheresoluBonofthewarfarineffectmaytakeseveraldays.
Switching from DOAC to VKA (Warfarin) ü RememberthatthefulleffectoftheVKAdoesn’tnotoccurforthefirstfewdaysdespiteprolongaBonofthePT/INR.
ü DabigatrantoWarfarinü Overlapthetwoagents.ThenumberofdaysofoverlapdependsontheptsrenalfuncBon.ü CrCl≥50–StartVKAthreedaysb4youd/cdabigatranü CrCl30to50–StartVKAtwodaysb4youd/cdabigatranü CrCl15to30–StartVKAonedaybeforeyoud/cdabigatran
ü RivaroxabanorApixabantoWarfarin-PrescribinginfosuggestsstoppingrivaroxabanorapixabanandprovidingaparenteralagentduringwarfarininiBaBonbecausetheINRcannotbemonitoredadequatelyduringadministraBonofadirectfactorXainhibitor.
Perioperative Management
Perioperative Mgt of Pts Receiving Anticoagulants
1. EsBmateThromboembolic(TE)Risk
2. EsBmateBleedingRiskduringtheprocedure
3. Determinethe&mingofan&coagulantinterrup&on
4. Determinewhethertousebridgingan&coagula&on
GeneralApproach
Estimate Thromboembolic (TE) Risk 1. HigherTEriskincreasesimportanceofminimizingintervalwithoutanBcoagulaBon.
2. MajorfactorsthatincreaseTEriskareAF,prosthe&cheartvalves,andrecentvenousorarterialTE(e.g.withinthepreceding3months).
3. AFpts:EsBmateTEriskbasedonageandcomorbidiBes.E.g.CHA2DS2-VASc
4. VTE(PEorDVT)pts:EsBmateTEriskbasedonintervalsincediagnosis.
5. IfTEriskistransientlyincreased(e.g.recentstroke,recentPE),it’sbesttodelaysurgeryunBlitreturnstobaseline,ifpossible.
6. Forptsw/morethanonecomorbiditythatpredisposestoTE,thecondiBonwiththehighestTErisktakesprecedence.
Estimate Procedural Bleeding Risk (BR) 1. BRisdeterminedmainlybytype&urgencyofsurgery.
2. Alsosomept.comorbidiBese.g.oldage,decr.renalfuncBonmayincr.BR.
3. MedsthataffecthemostasismayincrBR.
4. Categorizetheprocedureintominimalrisk,lowrisk,orhighBR.
Classifica?onofelec?vesurgicalproceduresaccordingtobleedingriskProceduresnotnecessarilyrequiringinterrup?onofDOACan?coagula?on(minimalbleedingrisk):Dentalprocedures(extracBonof1-3teeth,periodontalsurgery,abscessincision,implantmoving)Ophthalmology(CataractextracBon)EndoscopywithoutbiopsySuperficialsurgery(dermatologicexcisions)CentralvenouscatheterremovalProcedureswithlowbleedingrisk:GIendoscopy±biopsy,Bronchoscopy±biopsy,enteroscopy,biliary/pancreaBcstentwithoutsphincterotomy,endosonographywithoutfine-needleaspiraBonProstateorbladderbiopsyEPstudyorRFcatheterablaBonforSVT(includingleo-sidedablaBonwithtransseptalpuncture)Angiography(cardiaccath)PacemakerandcardiacdefibrillatorinserBon(ICDimplant)andelectrophysiologictesBngCarpaltunnelrepairCutaneousandbladder/prostate/thyroid/breast/lymphnodebiopsiesNoncoronaryangiographyCholecystectomyAxillarynodedissecBonHemorrhoidalsurgeryDilataBonandcurepageHydrocelerepairProcedureswithhighbleedingrisk:AnymajoroperaBon(procedureduraBon>45minutes)HeartSurgerye.g.CABG,HeartvalvereplacementComplexleo-sidedablaBonAbdominalaorBcaneurysmrepairSpinalorepiduralanesthesiaorinjecBons;lumbarpunctureVascularandGeneralSurgeryThoracicsurgeryAbdominalsurgeryMajororthopedicsurgerye.g.Bilateralkneereplacement,HipreplacementLiverorkidneybiopsyEndoscopicallyguidedfine-needleaspiraBonTURP(TransurethralprostateresecBon)Mostneurosurgicalprocedures(Laminectomy,etc)Neurosurgical/urologic/headandneck/abdominal/breastcancersurgeryPolypectomy,varicealtreatment,biliarysphincterectomy,pneumaBcdilataBon
Determine the timing of anticoagulant interruption
1. WhenshouldyougivethelastdoseoftheoralanBcoagulantbeforeprocedure?1. Dependsonthespecificagentused.
2. ForWarfarin,itis5daysbeforetheprocedure.
3. ForDOACs?
An?coagulant Renalfunc?onanddoseIntervalbetweenlastdoseandprocedure
NOTE:Noan?coagulantisgiventhedayoftheprocedure Resump?onaUerprocedure
Highbleedingrisk Lowbleedingrisk Highbleedingrisk Lowbleedingrisk
Dabigatran
CrCl>50Dose150mgBID
Givelastdose3daysbeforeprocedure(ie,skipfourdosesonthetwodaysbeforetheprocedure)
Givelastdose2daysbeforeprocedure(ie,skiptwodosesonthedaybeforetheprocedure)
Resume48to72hoursaoersurgery(ie,postoperaBveday2to3)
Resume24hoursaoersurgery(ie,postoperaBveday1)
CrCl30to50Dose150mgBID
Givelastdose5daysbeforeprocedure(ie,skipeightdosesonthefourdaysbeforetheprocedure)
Givelastdose3daysbeforeprocedure(ie,skipfourdosesonthetwodaysbeforetheprocedure)
Rivaroxaban
CrCl>50Dose20mgqd
Givelastdose3daysbeforeprocedure(ie,skiptwodosesonthetwodaysbeforetheprocedure)
Givelastdose2daysbeforeprocedure(ie,skiponedoseonthedaybeforetheprocedure)
CrCl30to50Dose15mgqd
Apixaban
CrCl>50Dose5mgBID Givelastdose3daysbefore
procedure(ie,skipfourdosesonthetwodaysbeforetheprocedure)
Givelastdose2daysbeforeprocedure(ie,skiptwodosesonthedaybeforetheprocedure)
CrCl30to50Dose2.5mgBID
Edoxaban
CrCl50to95Dose60mgqd Givethelastdose3days
beforetheprocedure(ie,skiptwodosesonthetwodaysbeforetheprocedure)
Givethelastdose2daysbeforetheprocedure(ie,skiponedoseonthedaybeforetheprocedure)
CrCl15to50Dose30mgqd
WhentogivelastdoseofDOACsbeforetheProcedure
Determine whether to use bridging anticoagulation
1. NobridgingnecessarywithDOACs(b/ctheyhaveshortert1/2.)
2. Mostptsdon’tneedbridgingb/citincreasesbleedingriskwithoutreducingtherateofTE.
3. OnlyafewptswithveryhighTEriskswhoaretakingwarfarinneedbridging.
4. Whenbridging,useLMWHformostpts.ExcepBonisptswithrenalinsufficiencyand/hemodialysis,forthose,useUFH.Don’tusedDOACsforbridging.
5. Timingdependsontheheparinproductusedandtheproceduralbleedingrisk.
Monitoring and Reversal
Monitoringü Warfarin:PT/INR
ü Heparin:aPTT;alsogetCBC(plts),CMP
ü LMWH:Laboratorymonitoringisnotnecessary.
ü DOACs:Don’tneedmonitoring.NoneoftheconvenBonalcoagulaBonassays(aPTT,prothrombinBme,INR,ACT)canbereliablyusedtomonitorDOACS.SomeoftheseassayswillbeaffectedorprolongedbytheDOACSbutnotinanypredictablemanner.
ReversalofDOACsü Only Dabigatran has a reversing agent: Idarucizumab (Praxbind) ü The rest have reversing agents in the works. ü Vitamin K does nothing ü Fresh Frozen Plasma does nothing ü Prothrombin Complex Concentrates (PCC) seem to work well but
are very expensive ü Despite lack of reversal agents, bleeding complications are no
more frequent and less severe than with warfarin
ReversinganBcoagulaBoninwarfarin-associatedbleedingManagementop?on Timetoan?coagula?onreversal Commentsandcau?ons
D/CWarfarin 5to14days FivedaysistypicalforpaBentswithanINRinthetherapeuBcrange
VitaminK* 6to24hourstocorrecttheINR,longertofullyreverseanBcoagulaBon
RecoveryoffactorsXandII(prothrombin)takeslongerthan24hoursRiskofanaphylaxiswithintravenousinjecBonImpairedresponsetowarfarinlasBnguptooneweekmayoccuraoerlargedoses(ie,>5mg)
Freshfrozenplasma DependsontheBmeittakestocompletetheinfusion;typically12to32hoursforcompletereversal
EffectistransientandconcomitantvitaminKmustbeadministeredPotenBalforvolumeoverload(2to4LtonormalizeINR)PotenBalforTRALIPotenBalforviraltransmission
Prothrombincomplexconcentrate 15minutesaoer10-minuteto1-hourinfusion
Effectistransient,andconcomitantvitaminKmustbeadministered;limitedavailabilityCostVariablefactorVIIcontentdependingontheproduct:a4-factorPCCispreferredPotenBallyprothromboBc
RecombinantfactorVIIa 15minutesaoerbolusinfusion
Effectistransient,andconcomitantvitaminKmustbeadministeredCostPotenBallyprothromboBc
MgtofaSupratherapeu?cINRINR Bleedingpresent Recommendedac?on*
>TherapeuBcto5.0 No
Lowerwarfarindose,or
OmitonedoseandrestartwarfarinatalowerdosewhenINRisintherapeuBcrange,or
NodosereducBonneededifINRisminimallysupratherapeuBc
>5.0to9.0 NoOmitthenextonetotwodosesofwarfarin,monitorINRmorefrequently,andresumetreatmentatalowerdosewhenINRisintherapeuBcrange,or
Omitadoseandadminister1to2.5mgoralvitaminK1¶
>9.0 No Holdwarfarinandadminister2.5to5mgoralvitaminK1.MonitorINRmorefrequentlyandadministermorevitaminK1asneeded.ResumewarfarinatalowerdosewhenINRisintherapeuBcrange.
Any Seriousorlife-threateningHoldwarfarinandadminister10mgvitaminKbyslowIVinfusion;supplementwithfour-factorprothrombincomplexconcentrate(4-factorPCC)orfreshfrozenplasma,dependingonclinicalurgency.Monitorandrepeatasneeded.
Emergentreversalofan?coagula?onfromwarfarinforlife-threateninghemorrhageinadults
4-factorprothrombincomplexconcentrate(4FPCC)isavailable(preferredapproach):
1.Give4FPCC1500to2000units¶IVover10minutes.CheckINR15minutesaoercompleBonoftheinfusion.IfINRisnot≤1.5,giveaddiBonal4FPCC(checkdrugreferenceorconsultpharmacyfordetails).
2.GivevitaminK10mgIVover10to20minutes.
B.3-factorprothrombincomplexconcentrate(3FPCC)isavailablebut4FPCCisnotavailable:
1.Give3FPCC1500to2000units¶IVover10minutes.CheckINR15minutesaoercompleBonoftheinfusion.IfINRisnot≤1.5,giveaddiBonal3FPCC(refertotopicordrugreferencefordetails).
2.GiveFactorVIIa20mcg/kgIVORgiveFFP2unitsIVbyrapidinfusion.FactorVIIamaybepreferredifvolumeoverloadisaconcern.
3.GivevitaminK10mgIVover10to20minutes.
C.Neither3FPCCnor4FPCCisavailable:
1.GiveFFP2unitsIVbyrapidinfusion.CheckINR15minutesaoercompleBonofinfusion.IfINR≥1.5,administer2addiBonalunitsofFFPIVrapidinfusion.RepeatprocessunBlINR≤1.5.MaywishtoadministerloopdiureBcbetweenFFPinfusionsifvolumeoverloadisaconcern.
2.GivevitaminK10mgIVover10to20minutes.
PCCproductsandwhateachcontainsUnac?vatedprothrombincomplexconcentrates(PCC)
4factor:• Kcentra ContaincoagulaBonfactorsII,VII,IX,andXininacBveforms
3factor:• BebulinVH• ProfilnineSD
ContainfactorsII,IX,andX(lipletonofactorVII)
Ac?vatedprothrombincomplexconcentrates(aPCC)
4factor:• FEIBANF ContainscoagulaBonfactorsII,VII,IX;factorVIIismostlyacBvated*
ReversalofHeparinsü Protamine Sulfate
Drug Interactions 1. DOACsareaffectedbyCytochromeP4503A4(CYP3A4)inhibitorsandinducersandbyinducersof
P-glycoprotein(P-gp)drugeffluxpump2. CytP4503A4inhibitorsinclude:
1. AnBfungalsendingin–azole,
2. AnBviralsoranBretroviralsendingin–vir,3. Macrolides
4. Non-dihydropyridineCCB–VerapamilandDilBazem5. Grapefruitjuice.
3. CytP4503A4inducersinclude:1. StJohn’swort2. Carbamazepine,Phenytoin
3. Etc
4. RefertoalistofdruginteracBonswhenusingmeds.
In Conclusion 1. Follow-upisessenBal
2. Assessadherenceandcompliance
3. Evaluateforbleedingandadverseevents
4. PeriodicchecksofrenalfuncBon,hemoglobin,andnewmedicaBonsthatcouldleadtoadverseinteracBon
1. All of the new oral anticoagulants are at least as effective as warfarin and can be given without routine monitoring.
2. All DOACs reduce the risk of intracranial bleeding 3. New agents produce about a 10% reduction in
mortality. 4. You don’t need bridging with DOACs. 5. Most pts on warfarin don’t need bridging.
Take Home Points
hpp://www.aafp.org/afp/2013/0415/p556.htmlAccessed05/2016hpp://www.aafp.org/afp/2016/0115/p130.html(PerioperaBveBridgingAnBcoagulaBonUnhelpfulforInvasiveProcedures)Accessed05/2016hpp://www.ncbi.nlm.nih.gov/pubmed/17904001Accessed05/2016hpp://www.beyondprinBng.com/thrombosis/pdf/Weitz.pdfAccessed05/2016hpp://www.uptodate.com/contents/warfarin-and-other-vkas-dosing-and-adverse-effectsAccessed05/2016hpp://www.uptodate.com/contents/perioperaBve-management-of-paBents-receiving-anBcoagulantsAccessed05/2016hpp://www.uptodate.com/contents/direct-oral-anBcoagulants-dosing-and-adverse-effectsAccessed05/2016hpp://europace.oxfordjournals.org/content/15/5/625Accessed05/2016hpp://www.uptodate.com/contents/heparin-and-lmw-heparin-dosing-and-adverse-effectsAccessed05/2016
Sources
Questions?
ANTICOAGULANTS KennethAcha,MDUCRSchoolofMedicineFMResidencyProgram05/12/2016