Interdisciplinaryapproachtoacomplexproblem;sicklecellanemia:achallenge

SundayOctober30th2016NASOM/GEMOQMeeting

ByDr.VeroniqueNaessens,MD,FRCPCHematologist,MUHC,MontrealQc

Disclosures

• Nonerelevant

Objectives

• Discusspre-conceptionplanningincludingmaternalrisksandmedicationuse,

• ReviewtheroleoftransfusioninpregnantSCDpatients,

• EstablishanappropriatemanagementplanfortreatmentandpreventionofmaternalSCDcomplications.

Introduction

• SickleCellDiseaseisthemostcommonsinglegenedisorder

• Estimatedrateof300.000births/year,200.000inAfricaalone.

• Affectsover20millionindividualsworldwilde

InterplaybetweenHemolysisandVasculopathy

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