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