Anti-thromboticsin patients with thrombocytopenia (and … · Anti-thromboticsin patients with...

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)





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).



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



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






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


A

5,90 4,631

6

Thrombotic Bleeding


B

5,81 6,22

1

6

Thrombotic Bleeding


*Physician-assessedriskonascaleof1-10(1=lowestrisk;10=highest)foragivencase

5,76 6,35

1

6

Thrombotic Bleeding


5,95 5,81

1

6

Thrombotic Bleeding


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…..






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






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


NO(92%)6,46 7,31

1

6

Thrombotic Bleeding


YES(8%)


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


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


42%LOWERDOSEby50%

(n=116)

LMWHIF40%

PROPHYLACTICDOSES(n=112)


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


30x109/Lin45%(n=54) 6,16 6,02

1

6

Thrombotic Bleeding


50x109/Lin48%(n=57)


“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)



Hakim,AmHeartJ,2011

Yusuf,Clin Cardiol,2012

Sarkiss,Cancer,2007

• Nofatalbleeding• BleedingcomplicationsnotassociatedwithsTP oraspirin



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