Post on 21-Aug-2018
Anti-thrombotics inpatientswiththrombocytopenia(andcancer)
MUMC+VascularRounds,Roermond,Nov2017
Avi Leader,MD• MaastrichtUniversityMedicalCenter,theNetherlands• HematologyInstitute,RabinMedicalCenter,PetahTikva,Israel
Geen (potentiële)belangenverstrengeling
Ihavenoconflictsofinteresttodeclare
Voorbijeenkomstmogelijkrelevanterelaties:
Bedrijfsnamen
• Sponsoringofonderzoeksgeld • NA
• Honorariumofandere(financiële)vergoeding
• NA
• Aandeelhouder • NA
• Andererelatie,namelijk… • NA
Disclosurepotentialconflictsofinterest: Avi Leader
• Background– BleedingRiskFactorsinThrombocytopenicCancerPatients(butnoAC)– Anticoagulationinnon-thrombocytopeniccancerpatients
• Antithromboticmedicationinthrombocytopenicpatients– Managementguidelines– Literaturereview– Knowledgegaps– Whydowedowhatwedo?
• Resultsofamultinationaldecision-makinganalysis
• Ongoingresearch:MATTERstudy(multinationalregistry)
• TakeHomeMessages
Agenda
• Degreeof(severe)TCPisnotclearlyassociatedwithbleeding– Otherfactorsmaycontribute:causeofTCP,medications,infection
• BleedingriskmayberelatedtolowHCTandcoagulationabnormalities.• Platelettransfusion(<10x10’9/L)areusedprophylacticallytoreduceclinically
significantbleeding
• Secondary(Post-hoc)analysisofpatientsenrolledinthePLADOtrial– >1200patientswithTCPd/tchemotherapyformalignancyorstemcelltransplant– PLADO=RCTassessingdifferentprophylactic(PLT<10)platelettransfusiondoses.– DailymonitoringofWHObleeding,DailyHCT,Hb,Plateletcount– aPTT,INRandfibrinogenatbaselineandwheneverelsetaken– Follow-up30daysafterfirsttransfusion.
LaboratorypredictorsofbleedingandtheeffectofplateletandRBCtransfusionsonbleedingoutcomesinthePLADOtrial
Uhl,Blood2017
Associationbetweenmorningplateletcountandgrade≥2Ableedingbystratum
• Thefollowinglabparameterswereassociatedwithincreasedbleeding:– PLT<5x10’9/L(≥2A;butnot≥grade3)– comparedto>80– HCT<25%(both)– comparedtoHCT>29%– INR>1.2(both)– aPTT >30seconds(≥2A;butnot≥grade3)
• Plateletcount,HCTandtreatmentstratumremainedsignificantpredictorsofbleeding(≥2A)inamulti-predictormodel(1).– OnlyHCT<25%associatedwithgrade ≥3
• Inmodel2,INRandaPTT areadded:onlystratum,aPTT andINRaresignificant.
• MorebleedingwithALLOthanAUTO/CHEMO• PlateletandRBCtransfusionsondaysofbleedingwerenotsufficienttochange
bleedingoutcomesthenextday.
ResultSummary
• Observationof<HCTandbleedingisconsistentwithanimalmodels– InterpretwithcareasRBCtransfusionqualifiesasgrade3bleeding.
• Findingssupportinvestigatingariskadaptedapproach.
• Limitations:– Limitedclinicaldata(i.e.confounders)– NoeffectofRBCandPLTTx onbleedingcouldbebecauseofconfoundingby
indication.– Timingofbleedingeventsnotrecorded– don’tknowifbeforeoraftertransfusion– Limitednumbersofgrade3-4bleeding– Nocoagulationtestsrequiredafterenrollment.Mayexplainwhyfindingsof
coagulationcontradicttheATHENAfindings(estcourt BJH,2014).• Theassociationbetweenphysicianorderedtestsandbleedingmaysimplyreflecttheteam’s
assessmentofcurrentbleedingwhichledtothetestbeingdone.–
Discussion
Anticoagulationinnon-TCPcancerpatientswithVTE
LMWHisstandardofcare.WHY?
CLOTstudy:benefitwithLMWHoverwarfarininVTE• RCTofdalteparin vsVKAfor6months
– PatientswithsolidtumorsandVTE
• ReducedrecurrentVTEindalteparin group(primaryEP)– 9%vs17%at6months(0.48;P=0.002)– Bleedingsimilar– Initial6mo.Analysisforallsubgroupsshowedsimilarresults
• ) Lee,NEJM2003
CATCHRCT: tinzaparin vs warfarin• Fulldosetinzaparin throughoutstudy• Included~10%hematologicmalignancies• recVTEin7,2%ofLMWH,and10.5%ofwarfarin(p=0.07)
Lee,JAMA2015
Bleeding• Samemajorbleeding
• Lessminorwithtinzaparin (HR0.58)
• Background– Anticoagulationinnon-thrombocytopeniccancerpatients– BleedingRiskFactorsinThrombocytopenicCancerPatients(butnoAC)
• Antithromboticmedicationinthrombocytopenicpatients– Managementguidelines– Literaturereview– Knowledgegaps– Whydowedowhatwedo?
• Resultsofamultinationaldecision-makinganalysis
• Ongoingresearch:MATTERstudy(multinationalregistry)
• TakeHomeMessages
Agenda
• ISTHSSC1 GL’s forcancerassociatedthrombosis(CAT)• 50%dose-reduction orprophylacticdosesofLMWHwhenPLT<50X
109/Lbut>25X109/L
• Discontinuation ofACwhenPLT<25X109/L
• Intheacutesetting:platelettransfusionstoenablefull-doseanticoagulation.IVCfiltersmaybeconsidered
• Data(andguidelines1,2)strictlyonLMWH(mostly)intheVTEsetting
1CarrierM.JThromb Haemost.2013;2LeeAY,etal.JCO.2009Oct10;27(29):4895-901
GuidelinesBaseduponexpertopinionandretrospectivedata
1. Commonproblemincancerpatients– 45% (!!)of197thrombocytopeniccancerpatientswerereceiving
antiplateletand/oranticoagulanttherapyinaprospectivecohort1
2. ProlongedchemoRx-inducedthrombocytopeniadoesnotprovideprotection againstVTE2– 34%ofVTEsoccurredwithPLT<50K– 13%whenPLT<20K.
3. Bleedingisaproblem– InHSCT,VTE is3-foldlesscommonthanclinicallysignificant bleeding3
1Vinholt,Platelets,2016;2KhanalN,etal.AmJHem,2016;3GerberD.E.etal.Blood2008
AntithromboticRxinThrombocytopenia
• ComplexanduncertainmanagementAnticoagulation– Practiceguidelines(venousthromboembolism)basedonexpertopinion– Varianceinreportedpractice2,3(e.g.platelettranfusion;holding/reducingdose)– Suggestivesupportivedataonsafetyofdosereduction4,5 andwithholdingRx6
Antiplateletmedication– Continuingaspirininacutemyocardialinfarctionandthrombocytopeniawas
associatedwithimprovedsurvival7.
• Whatarethemanagementstrategies?• Whatistheriskofbleeding/thrombosiswitheachstrategy?
AntithromboticRxinThrombocytopenia&Cancer
2Samuelson,Thromb Res2016; 3Chayaler,Transfusion2014;4Khanal;AmJHem,2016;5Mantha,JThrombThrombolysis,2017;6Li,BloodAdv 2017;7Feher,Oncologist2017
Table1: Summaryofestimatesofbleedingandthrombosisinthrombocytopenic(Plt<50K)cancerpatientsreceivinganticoagulation
PopulationACmanagement3
BleedingRecurrentThrombosis
Major ClinicallyRelevant Follow-up
Continue1 Stop Continue1 Hold Continue1 Hold Continue1 Hold Follow-up
HM2andacuteorpriorVTEa
(N=78)
58%• 55%nochange
• 3%dosereduced
42%
27% 3% 100daysfromTCP 2% 15% 100days
fromTCP
IRR10.12,95%CI1.50–432.60 IRR0.17,95%CI0.0–1.51
SCTandpriorVTE(N=204)b 65% 35% 3.8% 4.2% 30daysafterSCT 1.5% 1.4% 30days
afterSCT
HM2andacuteorpriorVTE(N=47)c
77%• 30%full• 47%proph.
17% 6.5%CIrate(95%CI2.2–19.5%))4
6months 14.8%CIrate(95%CI7–30.9%)
6months
Anycancer,priorVTEandatleast7daysPlt<50K
(n=140)d
19%• 14%reduced 63%
0%
?
0%
?
• 18%(25/140)alsohadmixedmanagement
Leukemia&ac.VTE(n=74)e 31% 69% 17.4% 29.4% ?
a)Houghton,Leuk &Lymph2017;b)Li,Bloodadvances2017;c)Khanal,AmJHem2016;d)Mantha,JThromb Thrombolysis,2017;e)Cox,abstractASY14.3ISTH2017
vs.ACContinued,if)45/13%(29bleedingandthrombosiswasComposite18% (6/33)ifstopped.(IRR1.83,95%CI0.65–5.86)at100daysfromTCP.
• 83patientswithacuteVTEandplt <50x109(ortransfusedfor≥50x109)within30days– Retrospectivechartreview | 30dayfollow-up.– 88%hadaplatelettransfusionthresholdof≥50x109
• 9%new/progressivethrombosis|37%bleedingevents(grade2ormore)|11%grade3-4• 13%hadtransfusionreactions.37%volumeoverloadrequiringdiureticsordialysis.
• Patientswhoexperiencedaplateletcountbelow50,000for>5dayshadhigherratesofminor(Grade2)bleeding,butnotmajorbleeding.– MostGrade2-4bleedingoccurredwithcountsabove50(median54)
• Negativeeffectspotentiallyrelatedtotransfusions– Transfusionreactionsandvolumeoverload– EarlydiscontinuationofACduetodifficultyadheringtogoal.
Platelettransfusionsnotwithoutriskinthesepatients
SamuelsonBannow,JThr Thrombolysis,2017
• RetrospectivereviewofrecordsatMSKCC(2015-2014)– HematologicalmalignancywithAMI
• Twogroupsbasedoncountsat1wk afterindexAMI– Plt >50Kvs Plt <50K– Plt <50Ksubdividedaccordingtoaspirinadministrationprofiles
• N=118.49%hadseverethrombocytopenia(sTP,plt<50K)– sTP pts wereyounger andhadmyeloidleukemiamoreoften– CVriskprofileandmedicationwassimilar– sTP pts weretachycardic,lowerHb,highertroponin– sTP lesslikelytoreceiveaspirin (43%vs 83%,p<0.001),thienopyridines andstatins– sTP hadHigherproportionofplatelettransfusions(79%vs 13%)
Feher,Oncologist2017
AntiplateletRx&thrombocytopenia
• PatientswithsTP whoreceivedaspirinhadamediansurvivalof96days,comparedwith17.5days inpatientswhodidnotreceiveaspirin(HR,0.44;95%CI,0.24–0.81).
Feher,Oncologist2017
AntiplateletRx&thrombocytopenia
Amongpatientswithacuteleukemia,acuteMIandPlt<50K:• Bleeding:– 19%(11/58)majorbleeding (BARC3a-c)overall.
• 16% (4/25)with aspirin and21% (7/33)without.• MedianFU=3.7yrs!!!
• Thromboticrisk– 6.9%(4/58)chanceofrecurrentMI
• 8%withaspirin vs.6.1%without
Antiplatelet medicationinTCP
Feher,Oncologist,2017
• sTP patientshaveworseclinicaloutcomesaspreviouslyshown
• Theconcernsforbleedingattheseplt countsarenotsupportedbyscientificevidence,hereandpreviously.
• Wedon’tknowhowtheplatelettransfusionsaffectedthisandwhatthethresholdshouldbe
• MostpatientshadPlt >30K.– Resultsnotvalidforlowercounts
Conclusion• TreatmentofAMIwithaspirin inpatientswithhematologicmalignanciesandsTP
isassociatedwithimprovedsurvivalwithoutincreaseinmajorbleeding
Feher,Oncologist2017
AntiplateletRx&thrombocytopenia
Friedmann,Transfus MedRev2002
• MaybeOKtowithholdACinpatientswithremoteVTE(>3monthstobeonsafeside)whohavethrombocytopeniapostautoHSCTa
• Riskofrec.thrombosis&maj. bleedingisfrom0%to15%&>20%,respectively.– Datadifficulttocomprehend.Butdefinitelythereisaclinicalproblem.
• Relationshipbetweenbleeding,plateletcountandACiscomplexandnonlinear.– Plateletthreshold/countwerenotpredictiveofbleedinginAutoSCT (Cr,bilirubinandPTwere)a– HighrateofAEsassociatedwithaplatelettransfusionthresholdof50× 109/Li.b
• Continueusingyourinstitutionalplatelettransfusionthresholds– butuseclinicallogicandrememberevidenceisweak
• ShouldtendtocontinueaspirininacuteMi c– Datamainlyforplt >30x109
Anti-thrombotics inTCP:Nopracticingchangingdata,but:
a)Li,Bloodadvances2017;b)Samuelson-Bannow,JThr thrombolysis2017;c)Feher,Oncologist2017
• Background– Anticoagulationinnon-thrombocytopeniccancerpatients– BleedingRiskFactorsinThrombocytopenicCancerPatients(butnoAC)
• Antithromboticmedicationinthrombocytopenicpatients– Managementguidelines– Literaturereview– Knowledgegaps– Whydowedowhatwedo?
• Resultsofamultinationaldecision-makinganalysis
• Ongoingresearch:MATTERstudy(multinationalregistry)
• TakeHomeMessages
Agenda
• Manyofthepreviousstudiesarenotlongitudinalanddon’tgiveyouinsightintothedynamicsofmanagement– measurelabparametersonlyduringbleedingoratdiagnosis
• Nodataonantiplateletdrugs,non-LMWHanticoagulationornon-VTEanticoagulationindications
• Retrospective• SingleCenter
Knowledgegapsforanti-thrombotics inTCP
Unmetneedforknowledgeonmanagementofantithrombotictherapyandassociatedbleedingandthrombosisoutcomesamong
cancerpatientswiththrombocytopenia.
• LeaderA,tenCateV,tenCate-Hoek A,Beckers E,Spectre G,Raanani P,SchoutenH,FalangaA,tenCateH.
• ASHannualconference2017,Posterpresentation#1106
Objectives1) Identifythepatientandphysiciancharacteristicsassociatedwith
anticoagulation(AC)managementstrategiesinTCPpatientswithhematologicalmalignancy
2) EvaluatewhetheraphysicianassessmentofbleedingandthromboticriskisassociatedwithACmanagement.
FactorsInfluencingManagementofAnticoagulationinThrombocytopenicPatientswithHematologicalMalignancy
• Casevignettestudyinamultinationalandmulticentersetting
1. Semi-structuredinterviewswith11hematologistsandthrombosis&hemostasis(T&H)specialistsinIsraelandtheNetherlands– “WhichpatientvariablesinfluencemanagementofACinthisscenario?”
2. Patientvariableswererefinedbaseduponthenumberofintervieweesselectingagivenoption
3. 5selectedattributeswith2-5levelseachwerethenenteredintoanalgorithmcreatingabalanced&reduceddesignfromafullfactorialmodel
Methods(1)
4. Themodelgenerated30clinicalcasesofTCPpatientswithdifferentpatientvariable combinations
5. Eachresponderreceived5ACcasevignettesandhadtochoose:1) nochangeinAC2) nochangeinACbuttransfuseplatelets3) holdAC4) modifyAC(i.e.ACclass/dose).
6. Thesurveywasthenre-piloted,designedasawebsite anddistributed viamailingliststonationalhematologyandT&HsocietiesinIsrael,theNetherlandsandItaly (N=886).
Methods(2)
• Managementwassplitinto3steps,eachwithachoicebetween2options
• Inmultivariateanalysis,mixedeffectsbinomiallogisticregressionmodels:
– CalculatedOR’sforusingaspecificstrategy(overtheother)foreachpatient/physician
variableincomparisontotheirrespectivereferencevariables
• Randomslopeswerecalculatedforthrombosisriskperceivedbyeachphysician.(i.e.by-subjectanalysistoaccountforrepeatedmeasures)– Thesewereincorporatedinthemixedeffectsmodel.
StatisticalAnalysis
• 168responders,inItaly(59),Israel(52),theNetherlands(47)andothercountries(10),answering774uniquecases.– 18% (158/886)ofpopulationdirectlycontacted,responded.– Medianprofessionalexperienceof15years[IQR=17]– Estimatedmedianof5patients[IQR8]withACandTCPpermonth.
• ACmodificationwasmadeby84%(141/168)ofuniquerespondersatleastonce.– ACwasheldby55%(93/168)– Nochangewith platelettransfusion=37%(62/168)– 42%(71/168)nochangewithout platelettransfusion
Results(1)
22%HOLD(n=167)
78%CONTINUE(n=607)
18%NOCHANGE(n=110)
vs.
82%INTERVENE(n=497)vs.
24%NochangebutTransfuse PLTs
(n=119)
76%MODIFY(n=378)
vs.C
Lowerplateletsof20,000/µL(vs.40,000/µL);priormajorGIbleeding (vs.none)andmanagement(vs.fellow)
Lowerplateletcounts of20,000/µL(vs.40,000/µL);higherriskACindications (vs.AF; CHA2DS2-VASc=2)
Lowerplateletcounts of20,000/µL(vs.40,000/µL);symptomaticPE,AConly(vs.AF;CHA2DS2-VASc=2);Dutchphysicians(vs.Israeli)
Italianphysicians(vs.Israeli)
5,82 5,93
1
6
Thrombotic Bleeding
RiskScale*(mean±SD)
3,866,84
1
6
Thrombotic Bleeding
RiskScale*(mean±SD)
A
5,90 4,631
6
Thrombotic Bleeding
RiskScale*(mean±SD)
B
5,81 6,22
1
6
Thrombotic Bleeding
RiskScale*(mean±SD)
*Physician-assessedriskonascaleof1-10(1=lowestrisk;10=highest)foragivencase
5,76 6,35
1
6
Thrombotic Bleeding
RiskScale*(mean±SD)
5,95 5,81
1
6
Thrombotic Bleeding
RiskScale*(mean±SD)
higherriskACindications (vs.AF;CHA2DS2-VASc=2);moreyrs ofexperience;expertiseintransfusionmedicine
Conclusionsondecisionmakinganalysis• Modifying ACtypeordosewasthemostfrequentmanagementactioninTCP.• Physician-assessedbleedingriskisauniversaldriverofmanagement,atall3steps,whilethrombotic
riskonlyaffectscontinuingACoverholding.
• DegreeofTCP istheonlyvariablepervasivelyassociatedwithmanagement,inlinewithcurrentguidelines.
• Priormajorbleedingand variousindicationsforACarevariablesnotrepresentedincurrentguidelines.• Thetime-since-eventcomponent,intheISTH-guidancewasnotreflectedinthisanalysis.
– Thiscouldmeanthatphysiciansdonotconsiderthiscomponent.
• Significantvariationsinmanagementbetweenindividualphysiciansandcountries.
• Suggestsoversimplificationbycurrentguidelines,reflectingtheneedforhigh-qualityprospectivedataonthishigh-riskgroup
• Currentfindingsarehypothesis-generating,andmustbeassessedinprospectivestudiesevaluatingtheclinicalrelevanceofthesecomponentsofthedecisionmakingprocess.– IfIweretoplanaprospectivestudyIwouldevaluatethesefactors…..
• Background– Anticoagulationinnon-thrombocytopeniccancerpatients– BleedingRiskFactorsinThrombocytopenicCancerPatients(butnoAC)
• Antithromboticmedicationinthrombocytopenicpatients– Managementguidelines– Literaturereview– Knowledgegaps– Whydowedowhatwedo?
• Resultsofamultinationaldecision-makinganalysis
• Ongoingresearch:MATTERstudy(multinationalregistry)
• TakeHomeMessages
Agenda
ManagementpatternsofAntiThrombotics andoutcomesinpatientswithhematologicalmalignancy
andThrombocytopEnia:aProspectiveRegistry
MATTERstudy
PI:Dr Avi Leader1,2;Collaborators:Dr ErikBeckers1,Profdr HarrySchouten1,Dr YvonneHenskens1, Prof.dr.AnnaFalanga3,Dr Galia Spectre2,Dr Arina tenCate-Hoek1,Prof.dr.HugotenCate1
1 MaastrichtUniversityMedicalCenter,Maastricht,theNetherlands;2 RabinMedicalCenter,PetahTikva,Israel3 HospitalPapaGiovanniXXIII,Bergamo,Italy
MATTERregistry:StudyDesign• Objective:Evaluatemanagementandfrequencyofbleedingandthrombosis,in
patientswithhemmalignancy,thrombocytopenia&antithromboticRx.
MainStudyQuestions1. WhatistheplateletthresholdatwhichantithromboticRxisheldorcontinuedat
baseline?
2. CalculatetheRRofbleedingorthrombosiswithcontinuing antithrombotictherapyvs.holdingtherapy
• CurrentStudyStatus: InitiationinDec2017
• Design:Prospectivemultinationalcohortstudy(clinicaltrials.gov:NCT03288441)
• Studypopulation:Patientsadmittedtotheinpatienthematologydepartmentoroutpatientclinic
StudyConceptRiskFactors• Bleeding• Thrombosis• General• Outcome-specific
AntithromboticRxManagement• Physiciancharacteristics• Physicianriskassessment• Managementdecisions
Outcomes• ArterialandVenousthrombosis
• Majorbleeding
• Inclusioncriteria(allthree)1. Hematologicalmalignancies(includingMDS)
• Withor withoutactivetreatment• Irrespective oftreatmentlineanddiseasestatus• Bothinpatientsandoutpatients
2. Currentorpredicteddiseaseortreatment-relatedthrombocytopenia (<50X109/L)ofanyduration.
3. Currentantiplateletand/oranticoagulanttreatment• Anyindication.AnyDuration• Atscreening(evenifstoppedatthatstage)
EligibilityCriteriaExclusionCriteria: 1)Previousthrombocytopenia(<50X109/L)withthecurrentantithromboticregimen;2)HIT/TTP/ITP
eCRF eCRF eCRF eCRF eCRFeCRF
Bld draw
Primary CompositeOutcome:1. ISTH-definedMajorbleedingeventsOR2. Symptomaticorincidentaldeeporsuperficialvenousthromboembolism
or arterialthromboembolism
SecondaryOutcomes:1. Nextmanagementintervention2. ISTH- definedClinicallyRelevantnon-MajorBleeding13. PlateletTransfusions(numberandadverseeffects)4. RBCtransfusions(number)5. Peaktreatmentintensity
– Anti-Xa /Dilutedthrombintime/INR/aPTT6. Wholebloodcoagulation:ROTEM(Estcourt,BJH2014)7. Death
StudyOutcomes
1Kaatz,JTH2015
• Background– Anticoagulationinnon-thrombocytopeniccancerpatients– BleedingRiskFactorsinThrombocytopenicCancerPatients(butnoAC)
• Antithromboticmedicationinthrombocytopenicpatients– Managementguidelines– Literaturereview– Knowledgegaps– Whydowedowhatwedo?
• Resultsofamultinationaldecision-makinganalysis
• Ongoingresearch:MATTERstudy(multinationalregistry)
• TakeHomeMessages
Agenda
Take home messages• Platelettransfusionthresholdsarenottheholygrail
– Therelationshipbetweenbleeding,plateletcountandACiscomplexandnonlinear.
AntithromboticRxinThrombocytopenia- DISCUSSION
• WhatdoYOUdo?– Dosereduction?– Transfusionthresholds
• AnticoagulationandAntiplatelet
• Wouldyoudaretoperformaninterventionalstudy?– …basedonthesedata
• Questions?
hyperlinks
IF anti-coagulantHOLD,thenWASanIVCFILTERrecommended?(n=167)
vs.
LEVELTWO(3)
1
3,646,81
1
6
Thrombotic Bleeding
RiskScale*(mean±SD)
NO(92%)6,46 7,31
1
6
Thrombotic Bleeding
RiskScale*(mean±SD)
YES(8%)
*Physician-assessedriskonascaleof1-10(1=lowestrisk;10=highest)foragivencase
Anti-CoagulantCases(+/- aspirin):LevelTWO(1)
• LowerthanthefiguresreportedinarecentpopulationbasedcohortintheUSA.• 19.6%of14,000cancerpts hadanIVCFplaced(Ho,Thr Res2015)• Only21%hadanobviousCItoAC!
• Mainsupportiveevidenceisforuseduringbleedingandnotin“highrisk”scenarios(White,Circulation2016)
5,05 6,5
1
6
Thrombotic Bleeding
RiskScale*(mean±SD)
IF anti-thromboticMODIFY,thenHOW?[sub-levelof“levelone(3)”]
vs.
Anti-CoagulantCases(without aspirin):LEVELTWO(2)
2
13%CONTINUENOAC atanydose(n=37)
87%CHANGETOLMWHatanydose(n=240)
vs.
5%CONTINUEVKAatanydose(n=13)
92%CHANGETOLMWH atanydose(n=255)
vs.
18%nochange
3%changetoDOAC
5,92 6,37
1
6
Thrombotic Bleeding
RiskScale*(mean±SD)
42%LOWERDOSEby50%
(n=116)
LMWHIF40%
PROPHYLACTICDOSES(n=112)
*Physician-assessedriskonascaleof1-10(1=lowestrisk;10=highest)foragivencase
NOACIF
VKAIF
Increasingthromboticrisk*;Dutchphysicians(vs.Israeli)
Lowerplateletcounts of20,000/µL(vs.40,000/µL)
IF anti-coagulantNOCHANGEBUTTRANSFUSEPLATELETS,thenHOW?[sub-levelof“levelone(2)”]
vs.
Anti-CoagulantCases(+/- aspirin):LEVELTWO(3)
3
IFPLATELETREFRACTORINESSdevelops andtargetnotreached
15%CONTINUEwithoutmodification(n=18)
85%HOLDanti-plateletregimenORLOWERINTENSITY(n=101)vs.
TRANSFUSIONTHRESHOLD?
5,69 5,521
6
Thrombotic Bleeding
RiskScale*(mean±SD)
30x109/Lin45%(n=54) 6,16 6,02
1
6
Thrombotic Bleeding
RiskScale*(mean±SD)
50x109/Lin48%(n=57)
*Physician-assessedriskonascaleof1-10(1=lowestrisk;10=highest)foragivencase
“BONUS”SLIDES(notpresented)
• DetailedStudyQuestions:– DescriptivePilotPhase– OutcomeAnalysisPhase
• Variabilityinmanagementofhematologicmalignancypatientswithvenousthromboembolismandchemotherapy-inducedthrombocytopenia• SamuelsonB,Gernsheimer T,Estey E,GarciaD.
• Surveyed24physiciansfrom19centers.• Onlyfocusedonanticoagulation inthecontextofVTE.
1. Whatwastheplateletcountabovewhichyouwouldbecomfortablewithfull/prophylacticdoseanticoagulation?
2. Threecasevignettes Samuelson,ThrombosisResearch,2016
AntithromboticRxinThrombocytopenia–Managementstudy
VariablePracticePatterns
Samuelson,ThrombosisResearch,2016
• Withheldanticoagulation,pendingplateletrecovery,forcatheter-associatedthrombosis
• Wouldtransfusetoaplateletthresholdof50,000/μL inordertoadministertherapeuticanticoagulation.
• Patientwhocan’tachieveaplateletcountof50,000/μL:• Mostdecreasethetransfusionthresholdto20,000/μL rather
thantodecreaseintensityofanticoagulation– HoldanticoagulationinfavorofIVCfilterplacement
Samuelson,ThrombosisResearch,2016
ClinicalScenarios– AcuteSymptomaticVTE
• 4-11%ofpts withAcuteMIhavethrombocytopenia– Plt <100KisassociatedwithearlyandlatemajorCVevents– Increasedmortality
• OnestudyshowedbenefitforaspirininPlt <100K,butseverethrombcytopenia wasunder-represented.
• Safetyofaspirinincancerpts withAMIandPlt <50Kisunknown– UnderusedinAMIandcancer– only46%
• Aim: Evaluatesafetyofbenefitofaspirininhematologicalmalignancypatientswithseverethrombocytopenia(<50K)
Feher,Oncologist2017
AntiplateletRx&thrombocytopenia
Hakim,AmHeartJ,2011
Yusuf,Clin Cardiol,2012
Sarkiss,Cancer,2007
• Nofatalbleeding• BleedingcomplicationsnotassociatedwithsTP oraspirin
Feher,Oncologist2017
AntiplateletRx&thrombocytopenia