ProthrombinComplex Concentrate for Major Bleeding on ...€¦ · Trauma related bleed 9 (26)...
Transcript of ProthrombinComplex Concentrate for Major Bleeding on ...€¦ · Trauma related bleed 9 (26)...
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Prothrombin ComplexConcentrateforMajorBleedingonFactorXaInhibitors:AProspectiveCohortStudySamSchulman,1 PeterL.Gross,1 BruceRitchie,2 SusanNahirniak,3 Yulia Lin,4 Lani Lieberman,5 MarcCarrier,6 MarkA.Crowther,7 IndyGhosh,8AlejandroLazo-Langner,9 MichelleZondag,11DepartmentofMedicine,McMasterUniversityandThrombosisandAtherosclerosisResearchInstitute,Hamilton,ON;2DepartmentofMedicine,and3DepartmentofLaboratoryMedicineandPathology,UniversityofAlberta,Edmonton,AB;4DepartmentofClinicalPathology,SunnybrookHealthSciencesCentreandDepartmentofLaboratoryMedicineandPathobiology,UniversityofToronto,ON;5DepartmentofClinicalPathology,UniversityHealthNetwork,andUniversityofToronto,Toronto,ON; 6DepartmentofMedicine,TheOttawaHospitalResearchInstituteattheUniversityofOttawa,Ottawa,ON;7DepartmentofPathologyandMolecularMedicine,Hamilton,ON;8DepartmentofEmergencyMedicine,TrilliumHospital,Mississauga,ON;9DepartmentofMedicine,WesternUniversity,London,ON,allinCanada
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BackgroundOralfactorXa inhibitorsareincreasinglyusedforanticoagulationbutthereisnoapprovedreversalagent.Prothrombin complexconcentrate(PCC)formanagementofXa-inhibitor-associatedbleedinghasbeendescribedinasmallcaseseries[1].Thedoseusedwas2100-4800units.ThedurationofbleedingafterpunchbiopsyinvolunteerstreatedwithedoxabanwasshortenedbyPCCinadose-dependentmanner[2]
MethodsDesignObservationalmulticentercohortstudyperformedathospitalsinCanadawherePCCwasreadilyavailableandwhereahospitalprotocolexistedthatsuggestedorrecommendedtheuseofPCCforreversalofdabigatran-associatedbleeding.Thestudywasoriginallyplannedfor35patientsbuthasnowbeenexpandedto60patients.StudypatientsAcuteandactivemajorbleeding(ISTHcriteria).Ontreatmentwithrivaroxabanorapixaban.TreatedwithPCC,2000units,asperhospitalprotocol.ExclusioncriteriaInitial useofadditionalhemostaticagents.DoNotResuscitate(DNR)ordergiven.Dropofhemoglobinwithoutsourceofbleeding.Acutecoronarysyndromeorischemicstrokeduringthepast30days.Refusaltoprovideinformedconsentfor30-dayfollow-up.StudyproceduresTreatingphysicianrequestsPCC(Octaplex,Octapharma® orBeriplex® P/N,CSLBehring)fromTransfusionmedicine.StudystaffisnotifiedthatPCCwasgiven.Consentobtainedfordatacollectionand30dayfollow-up.TreatingphysicianrateseffectivenessusinganAssessmentGuidemodifiedfromSarode etal[3].Intracerebralhematomavolumewascalculatedusing the4/3p abc formula[4].OutcomesEffectivenessoftreatmentSafety: arterialorvenousthromboembolism,assessedbyanindependentadjudicationcommittee
ResultsTimefromonsetofbleedingtoPCC:Median12.2h(IQR,5.7-30.2)ProlongedprothrombintimeorINR>1.2or↗anti-Xa in16patients(46%)PCC:Mean2077units(SD±539);25.9IU/kg(SD±8.3).AseconddosePCCwasgivento1patient.Effectivenesswasassessedin4 ways:Treatmentset(n=35)byresponsiblephysicianusingthemodifiedSarode AssessmentGuide:
Patients andantithrombotictreatment
Percent
Percent
Conclusion• ThereisnoapprovedreversalagentforfactorXa
inhibitors.• TheeffectivenessofPCCinmajorbleedingwas
assessedasGoodin66%,andModeratein17%.• Therewasone(3%)thromboembolicevent.
References1. Grandhi Retal.WorldNeurosurg.2015;84:1956-61.2. Zahir Hetal.Circulation.2015;131:82-90.3. Sarode R,etal.Circulation 2013;128:1234-43.4. BroderickJPetal.Stroke.1993;24:987-93.5. ConnollySJetal.NEngl JMed.2016;375:1131-41.6. Khorsand Netal.JThromb Haemost.2016;14:211-4.
Characteristic (n=35)
Age,yr 77.6(7.7)
Malesex,no.(%) 22(63)
Weight,kg,median(IQR) 81(66-90)
Creatinineclearance,mL/min,median(IQR) 65.4(35-90)
<30mL/min,no.(%) 2(6)
30to<60mL/min,no.(%) 8(23)
Indicationforanticoagulation,no.(%)
Atrialfibrillation
Venousthromboembolism
Bothindications
Ischemicstroke
29(83)
4(11)
1(3)
1(3)
Anticoagulanttreatment
Patientsonrivaroxaban,no.(%)
dailydose,mg,median(IQR)
timefromlastdosetoPCC,h
19(54)
20(17.5-20)
17.6(10.4)
Patientsonapixaban,no.(%)
dailydose,mg,median(IQR)
timefromlastdosetoPCC,h
16(46)
10(5-10)
18.4(12.1)
Resultsaremean(standarddeviation)unlessotherwisestated.
Bleedingcharacteristic (n=35)
Typeofbleeding
Intracranial
Intraspinal
Gastrointestinal
Intramuscular
Hemothorax
Retroperitoneal
Pelvichematoma
Hematuria
18(36)
1(3)
11(31)
1(3)
1(3)
1(3)
1(3)
1(3)
Traumarelatedbleed 9(26)
Criteriaformajorbleeding*
Criticalorgan
Overtbleed,transfused≥2u
Overtbleed,hemoglobindrop≥20g/L
21(60)
8(23)
18(36)
0
20
40
60
80
Good Moderate Poor
0
20
40
60
80
Good Moderate Poor
Post-hocanalysisusingtheISTHrecommendationfrom2016[6]
Post-hocanalysisofonlythe16patientswithprolongedPT/INR>1.2/↗anti-Xa
Percent
Post-hocanalysisofCNSbleedsusingtheoriginalSarode AssessmentGuide[4]vs.ANNEXA-4[5]
0
20
40
60
80
100
Exc/Good/Mod Poor/None
Thiscohort
Annexa4
Percent
0
20
40
60
80
Effective Ineffective
Safety: 1stroke (3%)5deaths (14%),4fromtheindexICH