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Interdisciplinaryapproachtoacomplexproblem;sicklecellanemia:achallenge
SundayOctober30th2016NASOM/GEMOQMeeting
ByDr.VeroniqueNaessens,MD,FRCPCHematologist,MUHC,MontrealQc
Objectives
• Discusspre-conceptionplanningincludingmaternalrisksandmedicationuse,
• ReviewtheroleoftransfusioninpregnantSCDpatients,
• EstablishanappropriatemanagementplanfortreatmentandpreventionofmaternalSCDcomplications.
Introduction
• SickleCellDiseaseisthemostcommonsinglegenedisorder
• Estimatedrateof300.000births/year,200.000inAfricaalone.
• Affectsover20millionindividualsworldwilde
Amultisystem,vasculardisease
BrainEyesTonsilsLungsHeartKidneysFertilityLiverSpleenSkinBones
Placenta?
Supportivecare
• Folicacidsupplementation• Analgesia
– Anti-inflammatories– Opioids
• Somepatientsareaffectedwithchronicpainsyndromeandrequiredailyopioids
• Ironchelationinpatientsunderchronic“top-up”transfusion
• Vaccines
Onlytworecognizeddisease-modifyingtherapiesexistinSCD…
• Hydroxyurea– Traditionallyusedtodecreaseratesofpaincrisisandacutechestsyndrome
– LinkedtoincreasedsurvivalinHbSS/Sbpatients– Generalizedchronicuseinreinforcedinnon-pregnantpatients
• Chronicbloodtransfusion– “Top-up”
• Longtermriskofironoverload
– Exchange(automatedormanual)
…MakingpreventivecarenecessaryforallSCDpatients
Ophtalmologyscreening q1-2years
Transthoracicechocardiogramq5years,ifnormal
EnsurevaccinationuptodateAnnualfluvaccine
OxygensaturationPulmonaryFunctiontestsIfanysymptomsorhistoryofACS
Annualurinanalysis
Liverfunctiontests q1year
TheconsensusstatementonthecareofpatientsWithsicklecelldiseaseinCanada
Canheam.org,2015
Pre-conceptionevaluation
• Laboratoryassessment:– CBC,reticulocytes,ferritin– Liverprofile– Urinanalysisandcreatinine
• Atbaseline,andrepeatq1-3monthsduringpregnancy
• Bloodbankevaluation– Bloodgroupandantibodyscreen– Redbloodcellphenotypeifnotpreviouslydone
• Retinopathyscreening• Transthoracicechocardiogram• Ensurevaccinationisuptodategivenfunctionalasplenia• Hemoglobinopathystatusofthepartner
Therapiesmustbealtered…
• Hydroxyureaiscontraindicatedinpregnancyandbreast-feedingwomen– Shouldbestoppedpriortoconception
• Paincontrol– NSAIDsroutinelydiscouragedinpregnancy
– Opioidsuseandfetalhealth
• Chelation,ifused,mustbestopped
…WhileSCDcomplicationsriseinpregnancy
Progressionofretinopathy
HigherrateofAcuteChestSyndrome
Progressionofnephropathy
HigherrateofVaso-occlusivepaincrisis
Higherthromboticrisk
Increasedrateofinfections
SCDinpregnancy
• WomenwithHbSShavea6foldincreasedriskofmaternaldeathcomparedtocontrols1
• Higherriskof:– Preeclampsia
– Stillbirth
– Pretermdeliveries
– Small-for-gestational-ageinfants
• LesserriskinwomenwithSCdisease
1Oteng-Ntim,etal.Blood2015
Istransfusioncureofallevil? RationaleforTransfusioninSickleCell
• Correctsanemia– IncreasesO2carryingcapacity(toacertainextent)
• DecreasestheproportionofHbScarryingerythrocytes– Reduceshemolysis
• ReducesbloodviscosityifRBCexchange
• Suppresseserythropoiesis(HbSsynthesis)iftop-uptransfusion
MaroufR.Bloodtransfusioninsicklecelldisease.Hemoglobin.2011;35(5-6):495-502ReesDC,WilliamsTN,GladwinMT.Sickle-celldisease.Lancet.2010Dec11;376(9757):2018-31
Usualtransfusionindicationsinpregnancyarethesameasnon-pregnantSCDpatients
Acutecomplications Chroniccomplications
Acutestroke Primarystrokeprophylaxis
Multiorganfailure Secondarystrokeprophylaxis
Severeacutechestsyndrome Multipleand/orsevereVOCand/orACS,despite/previousHydroxyureatherapy
Severeaplasticcrisis Chroniclegulcer
Pulmonaryhypertension
SCDnephropathy
SCDhepatopathy
Particularindicationsoftransfusioninpregnancy
• Multigestationalpregnancies
• EvidenceofIUGR
• Enhanceoxygencarryingcapacityforfetalindications– ThresholdfortransfusioninSCD?
Roleofprophylactictransfusioninpregnancy?
ShouldallSCDpatientsbetransfusedwhenpregnant?
• Resultsofameta-analysisof12studiesinvolving1291participants
• MalinowskiA.etal,Blood2015
• Heterogenousstudies– “prophylactictransfusiongroups”–variabletriggers:Hb<70andor%HbA<20-40%
– “on-demandtransfusiongroups”–variable“severeanemia”andsevereSCDcomplications
Comparison of mortality between the prophylactic transfusion and on-demand transfusion groups (A= maternal mortality; B= perinatal mortality).
Ann Kinga Malinowski et al. Blood 2015;126:2424-2435
©2015 by American Society of Hematology
Comparison of selected maternal morbidity indices between the prophylactic transfusion and on-demand transfusion groups.
Ann Kinga Malinowski et al. Blood 2015;126:2424-2435
©2015 by American Society of Hematology
Comparison of obstetric morbidity between the prophylactic transfusion and on-demand transfusion groups.
Ann Kinga Malinowski et al. Blood 2015;126:2424-2435
©2015 by American Society of Hematology
RisksassociatedwithtransfusionparticulartoSCDpatients
• Alloimmunization– ProphylacticprotectionagainC,E,Kellhasreducedtheriskofalloimmunization
• Ironoverload
• Hyperhemolysis
KeypointsregardingtransfusioninpregnantSCDpatients
• Indicationsfortransfusionsinacuteandchroniccomplicationsarethesameasinnon-pregnantpatients.
• ProphylactictransfusioninpregnantwomenwithSCDmayreducematernalmortality,vaso-occlusivepainevents,andpulmonarycomplications.
KeypointsregardingtransfusioninpregnantSCDpatients
• ProphylactictransfusioninpregnantwomenwithSCDmaysimilarlyreduceperinatalmortality,neonataldeath,andpretermbirth.
• Decisiontotransfuseprophylacticallyapatientduringpregnancymusttakeintoaccountthepatient’shistoryofSCDcomplicationsandriskoftransfusion,inparticular,historyand/orriskofredcellalloimmunization.
Conclusions
• PregnancyinSCDpatientsisassociatedwithanincreasedmaternal-fetalmorbidityandmortality.
• Pre-conceptioncounsellingmustincludescreeningofallSCDcomplications,carefulreviewofallmedicationsandadequatevaccination.
Conclusions
• TransfusionsduringpregnancyshouldbeofferedtopatientswithahistoryofsevereacuteorchronicSCDcomplications,orincertainfetalindications(IUGR,multiplegestation).
• ProphylactictransfusionforallpregnantSCDpatientsmaybebeneficial,butadditionalresearchisrequired.
• Amulti-disciplinaryapproachislikelytobebeneficialinpregnantSCDpatients.
Bibliography
• HowardJ.,Oteng-Ntim,Theobstetricsmanagementofsicklecelldisease,Bestpracticeandresearchclinicalobstetricsandgynecology,(26)2012
• Smith-Whitley,Reproductiveissuesinsicklecelldisease,Blood(124)2014
• AsmaS.,KozanogluI.,etal,Prophylacticredbloodcellexchangemaybebeneficialinthemanagementofsicklecelldiseaseinpregnancy,Transfusion(55)2015
• Oteng-NtimE.,MeeksD.,Adversematernalandperinataloutcomesinpregnantwomenwithsicklecelldisease:systematicreviewandmeta-analysis,Blood(125)2015
• MalinowskiA.,ShehataN.,Prophylactictransfusionforpregnantwomenwithsicklecelldisease:asystematicreviewandmeta-analysis,Blood(126)2015