VTE prophylaxis and procedural anticoagulation · Prophylaxis Key points •Total hip/knee...
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VTE prophylaxis and procedural anticoagulation: Focus on Orthopedic surgeries Sara Mahmoud, BPharm, PharmDcand, BCCCS, RPh Clinical Pharmacist, Al Wakra Hospital CPD office coordinator, Hamad Medical Corporation
Transcript of VTE prophylaxis and procedural anticoagulation · Prophylaxis Key points •Total hip/knee...
VTEprophylaxisandproceduralanticoagulation:FocusonOrthopedicsurgeries
SaraMahmoud,BPharm,PharmDcand,BCCCS,RPh
ClinicalPharmacist,AlWakra Hospital
CPDofficecoordinator,HamadMedicalCorporation
LearningObjectives:
• ListtheavailableanticoagulantsinHMCformulary
• ComparedifferentpharmacologicalagentsusedforVTEprophylaxisandtherapy
• ReviewCHESTandAAOSguidelinesinpreventingVTEinorthopedicsurgery
• Outlinetheguidelinesforinterruptinganticoagulationandbridgingtherapyinsurgicalpatients
PharmacologicalagentsusedforVTEprophylaxisandtherapy
Shortacting Maintenance therapyagents (long)
Onsetofaction Rapid Variable(warfarin: 5-7days)
Duration(Halflife) Short Long
Examples LMWH,UFH Warfarin,NOAC/DOAC
Coagulationcascade
LMWH
UFH
ShortactingEnoxaparin Dalteparin Unfractionated
Heparin(UFH)Mechanismof
actionInhibitfactorXa Inhibitantithrombin
III+factorXa
DosingProphylacticTherapeutic
40unitsOD SC1mg/kgBIDSC1.5mg/kgODSC
5000unitsOD SC120u/kgBIDSC200u/kgODSC
5000uBIDorTID80u/kgbolus
followed by18u/kgMonitoring Anti-factorXa aPTT q6hours
Pharmacokinetics Renalimpairment:reducedoseby50%
Lessaccumilated inrenalimpairment
Safeinrenalimpairment&
dialysis
MaintenancetherapyWarfarin Dabigatran Rivaroxaban
Mechanismofaction
Competes withVitaminKreceptorsonthelivertoformclottingfactors
Directthrombininhibitor
Direct FactorXainhibitor
Dosing ⋍ 5mg 150mgBID 15mgBID 21daysThen,20mgOD
Monitoring INR NA NATimetopeak 5-7days 1hr,(delayedbyfood
2hrs)2-4hrs
Halflifeelimination
20-60hours 12-17Hrs(elderly:14-17hrs)
5-9Hrs(Elderly:11-13hrs)
Prolongedbyrenalimpairment
Q:FACTORMYTH?
• ApatientistobestartedononeoftheNovelAnticoagulants(NOAC)today.ThepatientneedshortactingLMWHorbridgingtherapysuchasinwarfarin
cases?FACT/MYTH
MYTH!
Novelanticoagulantsexerttheireffectimmediatelywithoutrequirementofbridgingtherapy
VTEProphylaxis
VTEinsurgery
• VenousThrombo-embolism(VTE)isacommoncomplicationofsurgery
• PEisthemostcommoncauseofpreventabledeathinhospitalizedpatientsinsurgery
• PostoperativeDVTisoftenasymptomatic
• ItissuggestedthatroutinescreeningforDVThaslowsensitivity
• VTEoccursinabout3%ofpatientsundergoingorthopedicsurgerydespiteprophylaxis (highestintotalkneeandhipsurgeries)
• IncidenceofclinicallyevidentDVTis2-5%
VTEprevalenceaftermajororthopedicsurgeryinabsenceofprophylaxis
Procedure DVTTotal PE(Fatal)
Hiparthroplasty 42-57% 0.9-28%(0.1-2%)
Kneearthroplasty 31-85% 1.5-10% (0.1-1.7%)
Hipfracturesurgery 46-60% 3-11%(2.5-7.5%)
Answer:Pleasenotethatthesenumbersarebeforetheneweraofearlyambulationofsurgicalpatients
RiskfactorclassificationforVTEformationRisklevel CalfDVT Proximal
DVTClinical PE FatalPE
LowriskMinorSurgeryinpt <40yrs noriskfactors
2% 0.4% 0.2% <0.01%
ModerateriskMinorsurgeryinpatient +additionalriskfactors40-60yr oldpatient+NOriskfactors
1—20% 2-4% 1-2% 0.1-0.4%
HighriskSurgeryin>60yr old+additionalriskfactor
20-40% 4-8% 2-4% 0.4-1%
HighestriskSurgeryinpt >40yrsmultipleriskfactorsHip/Kneearthroplasty,hipfracturesurgery
40-80% 10-20% 4-10% 0.2-5%
RiskfactorsforVTEActivecancerPreviousVTE(except superficialveinthrombosis)Reducedmobility(3foldincrease)Elderly (>70yrs)Heart FailureoranyformofrespiratoryfailureAcutemyocardialinfarctionorischemicstrokeAcute infectionorrheumatological disorderObesity(BMI>30)
Ongoinghormonal therapy(oralcontraceptive)*
Criticalillness
Othersuggestedriskfactors- SIGNNHS
FamilyHistoryofVTEVaricoseveins
Raolixifene orTamoxifene (breastcancer)
Pregnancy(10foldincrease),Puerperium(post-partum:25foldincrease)
CentralVenousCatheter(11.5foldincrease)
ProphylaxisKeypoints
• Totalhip/kneereplacementsurgeryshouldbeplacedonDVTprophylaxis• Considerextendedprophylaxisinmajorsurgeries• Allothersurgeries:basedonclinicalappraisalofthepatient’sindividualriskfactors• AspirinisnotrecommendedforDVTprophylaxis• Inpatientswithincreasedriskofbleeding:usemechanicalprophylaxis• Somearticlesrecommendedacombinationofmechanicalandpharmacological
prophylaxis• TheAustralian&NewZealandworkingpartyonthemanagementofVTErecommend
toprescribeVTEprophylaxisexceptiftherearecontraindications(thrombocytopenia,elevatedINR,hepaticdisease,activebleeding,highriskofbleeding)
AgentsusedforVTEprophylaxisEnoxaparin Dalteparin Unfractionated
Heparin(UFH)Mechanismof
actionInhibitfactorXa Inhibitantithrombin
III+factorXa
Dosing 40unitsOD SC(obese)
5000unitsOD SC 5000uBIDorTID
Monitoring Nomonitoringrequired
Pharmacokinetics Renalimpairment:30mgdailySC
Lessaccumulatedinrenalimpairment
Safeinrenalimpairment&
dialysis
MechanicalVTEprophylaxis
Q:FACTORMYTH?
• ElasticstockingisequivalenttomechanicalcompressionsinDVTprophylaxis
MYTH!
ElasticstockingsshouldNOT beusedtopreventVTE,theyareinferiortomechanicalcompressions
GUIDELINESACCP,AAOS
CHESTguidelinesrecommendationsIndication Totalhip/kneearthroplasty orHipfracturesurgery
Recommendation
VTEprophylaxisforminimum10-14days
Agents Preferredagent:LMWH, UFHLessfavored:Fondaparinux,Dabigatran,Apixaban,Warfarin(INR2.5)- increasedriskofbleedingNostrongevidence:Aspirin,Pneumaticcompression
Pneumaticcompressions
Highriskofbleeding(previousmajor bleeding,renalfailure,antiplateletagent,surgicalbleedingrisk)Compliance shouldbefor18hrsperday
Timing ForLMWH,initiate12hoursbeforesurgeryResume12-24hourspostsurgery(lessriskofbleeding)
CHESTguidelinesrecommendations
Indication Majororthopedicsurgery
Recommendation VTEprophylaxisfor35daysvs10-14days
Agents Preferredagent:LMWH, UFHLessfavored:Fondaparinux,Dabigatran,Apixaban,Warfarin(INR2.5)- increasedriskofbleedingNostrongevidence:Aspirin,Pneumaticcompression
Recommendation CombinationofpharmacologicalandmechanicalprophylaxisBasedoncochrane meta-analysis
NoncompliancetoIPCD
Dabigatran/Apixaban
Recommendation DopplerUltrasoundscreeningforpatientspostmajororthopedicsurgery
QUESTION:WHATISTHEPREFERREDVTEPROPHYLAXISAGENTBASEDONTHEGUIDELINES?
• LowMolecularWeight(Enoxaparin/Dalteparin)
• UnfractionatedHeparin
• Apixaban
• Dabigatran
• Aspirin
• Warfarin
• Fondaparinux
• Rivaroxaban
• Pneumaticcompression
Answer:LowMolecularWeightHeparin
20%reductioninDVTin favorofLMWH
Equivalent,notenoughdataaboutbleeding
Equivalent,butusedhigherdoseDab.
Comparedveryhighdose,moreDVT
LessasymptomaticDVTwithLMWH
IncreasedbleedingeFond.
Inc.riskofmajorbleeding
LessbleedingwithIPCD,non-inferior
DOSINGOFNOAC INORTHOPEDICSURGERY
Kneereplacement Hipreplacement
Dabigatran 110mggiven1-4hoursaftersurgery
110mggiven1-4hrsaftercompleting
surgeryRivaroxaban 10mgdaily
10-14 daysUpto35days
10mgdaily10-14days
upto35days
NoProphylaxis
Indication Isolatedlower leginjurythatrequiresimmobilization
Indication KneearthroscopywithnohistoryofpriorDVT
Therapeuticanticoagulationandproceduralguidelines
ANTICOAGULATION
• Anticoagulationistheprocessofbloodthinning.Thisisusedtopreventclotformationincertaindiseasessuchasatrialfibrillation,valvereplacement,thrombosis.Itisalsousedtotreatcertainconditionssuchasacutedeepvein
thrombosis,pulmonaryembolismoranyformofthrombosis.
INDICATIONSFORANTICOAGULATION
• Non-Valvular Atrialfibrillation*
• Valvular heartdiseaseandprostheticheartvalves
• Mechanicalvalvevstissuevalve
• Venousthromboembolism(DVT,PE,Otherthrombosis…)
• Inheriteddisease(proteinC,Sdeficiency)
• Autoimmunediseasesrelatedtoincreasedthromboticrisk(antiphospholipidsyndrome)
DOALLPATIENTSWITHAFREQUIREANTICOGAULATION?
• No
DECISIONTOANTICOAGULATION
RiskofthrombosisCHAD-VAS2score
RiskofbleedingHASBLEDscore
CHA2DS2-VASCSCORE
C Congestive heartfailureH Hypertension(>140/90orontherapy)A2 Age>75yearsD DiabetesS2 Priorstroke orTIAV Vasculardisease(PAD,MI,…)A Age65-75Sc Gender (Sexcategory):Female
RISKOFTHROMBOSISBASEDONCHAD2VASC2
0 01 1.3%2 2.2%3 4%5 6.7%6 9.8%7 9.6%8 12.5%9 15.2%
HAS-BLEDSCORE
H Hypertension (SBP>160) 1
A Abnormal renalfunctionAbnormalhepaticfunction
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S Stroke: priorhistoryofstroke 1
B Bleeding:priorhistoryofmajor bleeding 1
L LabileINR(unstable)
E Elderly>65 1
D Prioralcohol,medsthancanpredisposebleeding(NSAIDs,antiplatelets)
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INTERRUPTIONOFANTICOAGULATIONANDBRIDGINGINSURGERY
Riskofbleedinginthesurgicalprocedure Riskofthrombosis
High(especiallymechanicalvalve)*
LowHighLow
Donotinterruptanticoagulation
Interruptanticoagulation Bridging Nobridging
WARNING!
• Epiduralanaesthesia:DoNOTuseanyoftheNOACbecauseoftheincreasedriskofspinalorepiduralhematoma• Resume24hoursafterremovalofepiduralcatheter
INTERRUPTION- WARFARIN
Agent INR>3(abovetarget)*
INR2-3(therapeutic)
INR<2(sub-
therapeutic)Warfarin Discontinue>5
daysbeforesurgery
Discontinue5daysbeforesurgery
Discontinue 3-4daysbefore
surgery
CheckINR24hoursbeforesurgery
INTERRUPTION- DOAC
Agent Lowbleedingrisk(surgery) Intermediate orhighbleedingrisk(surgery)
Dabigatran Cl >80:>24hrsCl50-79:>36hrsCl30-49:>48hrsCl:15-29:>72hrs
Cl<15:Nodata>96hrs*
Cl>80:>48hrsCl50-79: >72hrsCl:30-49:>96hrsCl:15-29:>120Cl<15:Nodata
Rivaroxaban Cl>30: >24hrsCl15-29:>36hrsCl<15:Nodata,
Consideranti-Xa level
Cl>30:>48hrsCl<30:Nodata
Surgerybleedingrisk
Renalfunction
EMERGENCYSITUATION
BRIDGING
AGENTSUSEDINBRIDGING
Lowmolecularweightheparin Unfractionatedheparin
MoreconvenientMaynotrequiremonitoring Safestoptioninrenalimpairment
Monitoring:aPTT q6hrs thenq12whendoseisdetermined
RenalImpairment+Obese:MonitorantiFactorXa levels
DOSING
Enoxaparin Dalteparin UFH
Dose 1mg/kg BIDOR1.5mg/kgdaily
120u/kg BIDOR200u/kgdaily
80u/kg bolusfollowedby18u/kgadjustedbasedonapTT
RenalImpairment Reducedose50%Cl<30:MonitorDialysis: Notapproved
Lessaccumilated SAFE!
Monitoring AntifactorXa aPTT q6hrs
KEYPOINTSINBRIDGING
• WhenINR<2,initiatebridgingtherapy
• NextscheduleddoseNOAC
• HoldUFH4hoursbefore
• HoldLMWH12hrs before
• HeparinInducedthrombocytopenia:Lepirudin
• Neverinitiatewarfarininpaient withHITaslongasPLT<50
RESUMING- POSTSURGERY
• Basedonpostproceduralbleedingrisk:
• Warfarin24-48hours
• Warfarin:Bridgeifrequired(basedonCHADVASandHASBLED)
• UntilINRistherapeutic>2formorethan24hoursorafter5dayswhicheveriscloser
• NOAC:Donotbridge
• ResumeNOAC:24hrs (lowpostproceduralbleedingrisk)
• ResumeNOAC:48-72hours(Highpostproceduralbleedingrisk)
REFERENCES
• G.Agnelli,PreventionofVenousThromboembolisminSurgicalPatients.Circulation.2004;110[supplIV]:IV-4–IV-12
• CHESTguidelinesVTEprophylaxisinorthopedicsurgery2012
• AAOSguidelinesVTEprophylaxis
• ACCguidelinesforbridgingtherapyinnon-valvular AFpatients2017
• CHESTguidelinesforpreandpostproceduralanticoagulation
