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What is New for 2011:

What is New for 2011:. Anticoagulation in. Older Surgical Patients. Laurie G. Jacobs, MD. Professor of Clinical Medicine. Peri-Operative Anticoagulation. • New Anticoagulants • VTE prophylaxis. • Chronic anticoagulation for AF and implications for peri-operative care.

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What is New for 2011:

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  1. WhatisNewfor2011: Anticoagulationin OlderSurgicalPatients LaurieG.Jacobs,MD ProfessorofClinicalMedicine

  2. Peri-Operative Anticoagulation •NewAnticoagulants •VTEprophylaxis •ChronicanticoagulationforAFand implicationsforperi-operativecare •Peri-operativemanagement

  3. PointsofAction ofAnticoagulants apixaban,rivaroxaban,edoxaban, otamixaban,betrixaban,YM150,TAK442 Xa X Warfarin Fondaparinux Heparin,LMWH Hirudin,bivalirudin, Argatroban,dabigatran Platelet activation Prothrombin(II) Fibrinogen Thrombin(IIa) Fibrin venous thrombosis arterial thrombosis

  4. NewOralAnticoagulants

  5. IndependentRiskFactors forFirstVTE RISKFACTOR Adj.pop.Attrib.risk* 95%CI Hospitalizationornursinghome Hospitalizationwithsurgery Hospitalizationwithoutsurgery Nursinghome Activemalignantneoplasm Trauma Congestiveheartfailure Priorcentralvenouscatheterorpacemaker Neurologicaldiseasew/extremityparesis Priorsuperficialveinthrombosis 58.8 23.8 21.5 13.3 18.0 12.0 9.5 9.1 6.9 5.4 53.4-64.2 20.3-27.3 17.3-25.6 9.9-16.8 13.4-22.6 9.0-14.9 3.3-15.8 5.7-12.6 3.5-10.2 3.0-7.7 HeitJA,etal.ArchInternMed.2002;162:1245-1248. *age,sex,yr

  6. RiskFactorsforVTE •Stasis • Advancedage •Hypercoagulability • Immobility(bedrest>4d) • • • • • • CHF,severeCOPD Stroke,paralysis,casting SpinalcordInjury Increasedviscosity Obesity Varicoseveins • • • • • • Advancedage Activecancer Highestrogenstates Thrombophilia Inflammatorystates Surgery • Increasedbloodviscosity •EndothelialDamage • Surgery,esp.orthopedic • PriorDVT,PE • Centrallines,devices • Trauma

  7. AgeDistributionof DVTPatients 30 HospitalizedMedicalPatients HospitalizedNonmedicalPatients 25 20 15 10 5 0 Percentage 1-20 21-30 31-40 41-50 51-60 61-70 71-80 81-90 >90 Age(years) PiazzaG,etal.Chest.2007;132:554-561.

  8. Peri-operative Hypercoagulability •VTEriskfactorsprevalentinsurgicalpatients •VTERiskis100Xgreaterthaninnon-operative period Plasminogenactivatorinhibitor-1 Hypercoagulability Stasis Endothelialdamage •“ReboundHypercoagulability”withdiscontinuation oforalanticoagulants thrombin-AT[TAT]complexes d-dimer prothrombinfragmentsF1&2 fibrinopeptideA factorVIII

  9. VTERisk&Prophylaxis GeertsWH.CHEST2008;133:381S

  10. DVTProphylaxis •Non-pharmacological Methods •Anticoagulants •Heparins –SCUFHeparin –LMWH –fondaparinux •Warfarin •Newagents: –FactorXainhibitors • • • • compressionstockings legelevation earlymobilization intermittentpneumatic compression •Footpumps –DirectThrombininhibitors

  11. VTEProphylaxisinTHR *Apixaban2.5mgpobid;12-24hpostop **Enoxaparin40mgsc12hpreop,thenpostop ADVANCE-3;pts.Followed60+daysafterlastdose LassenMR,etal.NEnglJMed2010:363:2487-98

  12. VTEProphylaxis: GeneralSurgeryBleedingRisk Prophylaxis Injectionsitebruising6.9% Woundhematoma5.7% Drainsitebleeding2.0% Hematuria1.6% GIbleeding0.2% Retroperitonealbleeding<0.1% Discontinuation2% Surgicalintervention0.7% Control 2.8% 0.8% 0.6% 0 1.9% 0 0 0.7% Meta-analysis:52RCTsVTEpx(33,813pts) LeonardiMJetal.ArchSurg2006;141:790-99.

  13. Indicationsfor ChronicAnticoagulation •ArterialDisease •Atrialfibrillation •RecurrentSystemic Embolism •MechanicalHeart Valves •Rheumaticmitral disease(&hxSE,AFor LAdiam.>5.5cm) •VenousDisease •ProphylaxisofVTE •SecondaryPrevention (Treatment)ofVTE –Deepvenous thrombosis –Pulmonaryembolism

  14. Warfarinv.Dabigatran forAFStrokeorSE(Re-Ly) RandomizedEvaluationofLongTermAnticoagulationTherapy Cumulative hazardrate months Dabigitran150mg;TTR44-70%;Reductionsincompositecardiovascularendpointsandmortality btwndabigatranandwarfarinareattenuatedbyINRcontrol ConnollySJetal.NEnglJMed2009;361:1139-1151

  15. Peri-OpDecision-Making: ChronicAnticoagulation BleedingRisk •Individualbleedingrisk •Surgicalriskforbleeding ThromboembolicRisk •Indication –Mechheartvalve –Atrialfibrillation –Venousthrombosis •Individualriskfactors •Surgicalriskfactors

  16. RiskStratificationfor Thromboembolism Geertsetal.Chest2001:119:132S-175S;Douketisetal.Chest2008;133:299-339

  17. Peri-OpAnticoagulation inNonCardiacSurgery Douketisetal.Chest2008;133:299-339

  18. Peri-operativeEvents withAnticoagulation •MechanicalHeartValveStudy1 •556pts/580procedures:372Ao,136Mitral,48multiple;warfarin d/c4-5daysprior,restartedafterhemostasis,bridging.At3mos: •0.9%thromboembolism •3.6%majorbleeding •nodifferencebwtnbridging,andtypeofac •GeneralSurgeryStudyofACPatients2 •603surgicalpatientsonwarfarin,themajorityofwhomdidnothave interruptionoftherapypriortosurgery •Peri-operativemajorbleeding9.5%(7.1–12.1) •Oddsratio1.6(0.4–4.0)ifINR3.0vs.2.0 1DanielsR,etal.ThrombRes2009;124:300-5;2TornMetal.BrJHaematol2003;123:676–82

  19. GuidelinesforSurgery onAC

  20. InterruptionofOral Anticoagulation: ElectiveSurgery •Discontinuewarfarin5dayspriortosurgery –mayneedtodiscontinueearlierwithmechanicalvalves asINRfallsfromagreaterlevel –INRfallsmoreslowlyintheelderly •CHECKINRbeforesurgery;INRfalls exponentiallywithwidevariabilitybetween patients,slowerwithage •IfINR>1.5pre-opday1-2,administer1–2mg oralvitaminK(comesas5mgtab,thuswould give½taborscdose) Douketisetal.Chest2008;133:299-339

  21. Resumptionof AnticoagulantTherapy •Mayresume12-24hourspost-op(eveningof,or dayafter)orwhenhemostasisisestablished •~48hrsrequiredforapartialanticoagulanteffect (INR>1.5) •Ifresumeatpatient’spriordose,~5.1+1.1days toachieveatherapeuticINR •Ifresumewithdoublepatient’susualdoseforday 1–2,atherapeuticINRisachievedat4.6days

  22. BridgeTherapy Pre-operativePeriod •Ifpre-opINR2-3,lastdosewarfarin5daysbeforesurgery (hold4doses); •Ifpre-opINR3-4.5(orelderly),lastdose6daysbefore surgery(hold5doses) •StartLMWH36hrsafterlastwarfarindose –Enoxaparin1mg/kgscorDalteparin100IU/Kgq12 –Lastdose½doseLMWH~24hpriortoprocedure •Writtenplanforpatient,internist,surgeon,anesthesiologist •Phonenumberforquestionsoranemergency Jafferetal.CCJM2003;70:973 WhiteRHetal.AnnInternMed1995;122:40-2

  23. BridgeTherapy Post-op •Afterdiscussionwithsurgeon,restartLMWH~24hrs post-operatively(withhemostaticcontrol) –fulldosesforminorsurgeries –prophylacticdosesforday1-2ifhighbleedingrisk •Afterdiscussionwithsurgeon,startwarfarinatpre-op doseonpost-opday1 •DailyPT/INRuntildischargeandperiodicallythereafter untilINRistherapeutic(ongoing) •CBCwithPlateletcountday3and7(HITscreening) •DiscontinueLMWHwhenINRisintherapeuticrangefor twoconsecutivedays(oftenINR2-3)

  24. LMWH&Regional Anesthesia(orAnalgesia) •Pre-operatively •Otheranticoagulantsheld(andclopidogrel,perhapsalso asa) •Needleplacement –12hrsafterprophylacticLMWH –24hrsafterLMWHifdose>1mg/kg •Post-operatively • • • • Indwellingcatheterremovedprior totwicedailyLMWH Removecatheter12-24hrsafterlastdoseLMWH FirstdoseLMWH2hrsaftercatheterremoval IfusingoncedailyLMWH,firstdose6-8hrspost-op, seconddose24hrslater HorlockerT.RegAnesthPainMed2003;28:172-97 ASRA.comAmericanSocietyofRegionalAnesthesiaandPainMedicine

  25. Anti-PlateletAgents andSurgery •Aspirin –Irreversiblyinhibitsplateletcyclooxygenase –Circulatingplateletpoolreplaced7–10days –Actswithinminutes •Clopidogrel(thienopyridines) –InhibitsADPreceptor-mediatedplateletactivationandaggregation –Stop7daysbeforesurgery –Mayrequireloadingonrestarting300-600mg;takes3–7daysto reachpeakanti-plateletaggregationactivityon75mgdose •NSAIDS –Reversiblyinhibitplateletcyclooxygenase;COX-2inhibitorshave lesseffect –Inhibitrenalprostaglandinsynthesissocanworsenrenalfailurewith otherdrugs

  26. AntiplateletAgentsand PerioperativeRisk •Cannoteasilymeasurebleedingriskwithantiplatelets •Individualvariabilityinbleedingriskwithantiplatelets •Iflowcardiacrisk,nostents,noncardiacsurgery,may electtostopASAorclopidogrel7–10dayspreop; resume24hrspostopwithadequatehemostasis •Forhighcardiacrisk,noncardiacsurgery,continueASA to,andaftersurgery •Forcardiacsurgery,orforpatientswithcoronarystents, consultcardiologyandguidelines(ACCP,ACC/AHA)

  27. NewAnticoagulants andSurgery •NewAgents •Maynotsubstantiallychangethromboticrisks; howeverifadherenceispoor,thismayincrease •Maynotsubstantiallychangebleedingrisk •Mayeliminatetheneedformonitoring •Mayeliminatetheneedforbridgingwhen patientscantakep.o.medications •Mayincreasethenumberofpatientsonchronic anticoagulationduetoeaseoftherapy

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