Presentation Management of Thrombotic Thrombocytopenic Purpura

8/17/2019 Presentation Management of Thrombotic Thrombocytopenic Purpura

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Rangga Lunesia

Management of thromboticthrombocytopenic purpura :

Current Perspective


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Abstract TTPRare ( 6 cases/mill/y in !"

Life threatening

n#erlying path: #ef$ A%AMT&'activitycleaves ultralarge von )illebran#factorAc*uire# : autoantibo#y me#iate#

Congenital : #eletarious mutations


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+ntro#uction TTPAggressive form of thrombotic

microangiopathy microvascular ischemia multiorgan #ysfunction

,igh morbi#-mortal promptly treate#


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Pathogenesis . Terminology A%AMT&'0 cleave Lv)100

multimer to smaller

v)1 as bri#ge bet2een e3pose#suben#othelial matri3-platelet4 after vessel

in5uryessel in5ury7n#othelial cells secrete#

Lv)1 multimer

A%AMT&' activity 8 99 Lv)1 multimere3cession 8 bin# to platelet (platelet richthrombi" 8 platelet aggregation 8 partialvessel occlusion 8 organ ischaemia


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&evere A%AMT&' activity #eciencyAutoantibo#y bin#s to an# impairs its

function (;


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%iagnosisClinical PresentationClassic penta# : fever4 thrombocytopenia4

microangiopathic hemolytic anemia4 renal#ysfunction4 neurological symp$


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Laboratory assays A%AMT&' en>yme activity('?="

The other investigation that routinely performe# in TTP :

•

@loo# lm4 reticulocyte count4 bilirubin4 haptoglobin• Prothrombin time4 activate# partial thromboplastin time4

brinogen

• Liver function test4 electrolytes4 urea an# serum creatinine4serum troponin4 calcium4 thyroi# function test

•

,+ serology4 hepatitis @ an# C serology• Autoantibo#y screen

• Pregnancy testing

• %irect antiglobulin test4 cytomegalovirus serology

• CT/MR+ brain4 echocar#iogram4 7!

•

Bther imaging to e3clu#e malignancy


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Management of TTPAC+R7% TTPClinical instability4 su##en4 rapi#4 unpre#ictable

#eterioration

'st4 resuscitation4 maDe sure any critical organ#ysfunction stabili>e#$

Then4 #eci#e4 by the rarity of TTP4 consi#ermanage# in e3perience# centrali>e# institution forhematologists4 intensive care physicians4A%AMT&' test$

Bnce suspecte#4 if theres any intense nee#(centralvenous line placement4 plasma e3change"4resuscitation re*uire#4 or clinical instability 2ithin EFhrs4 consi#er a#mission to +C/hi #epen#ency nit$


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Plasma 73change(P7G"Most important for acute +nitiate# 2/o #elay for suspecte# patient$Re#uce# #eath rate&uperior to plasma infusion alone (still use# for tempori>ing

in case of unavoi#able #elay to P7G"

P7G is initiate# at '$es (9'


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arious options for replacement Kui# #uringP7G : cryosupernatant (C&P"4 fresh fro>enplasma (11P" or solvent/#etergentItreate#poole# plasma (&%P"

Bur stan#ar# : Bctaplas (fe2er allergicreactions than 11P/C&P"

+n the case that Bctaplas is not available411P is usually use# #ue to its generalavailability


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Ritu3imab&afe4 eective for ne2ly #iagnose#$ P7G re*uire# to achieve remission risD of relapse by ?=

The sche#uling of ritu3imab is E< mg/mFiv/2eeDly for J 2eeDRitu3imab remove# from circulation by P7GA#minister Ritu3imab immediately after P7G to

maximize its #uration of action being remove#by subse*uent P7GAvoi# P7G for 9 'F hrs after a#ministration

Ritu3imab


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Corticosteroi#sRapi# immunosuppression

No rm evi#ence base to gui#e the choice ofsteroi#$

1avor : methylpre#nisolone + '? mg/Dg/#ay$Bur stan#ar# : methylpre#nisolone ' g iv/#ay

for # ('st #ose imme#iately a#ministere#after 'st P7G"


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&upportive CareAntiplateletPlatelet 9


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Bther +nterventionshas such limite# role e$g$:Bther immunosuppressant :mycophenolate mofetil4

cyclosporine4 vincristine (yet no high *uality #ata

regar#ing its eOcacy"&plenectomy : for relapsing #isease (little goo#

evi#ence for its eOcacy"


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CBN7N+TAL TTP%eleterious mutations 2ithin the ADAMTS13 gene$Autoantibo#ies against A%AMT&' do not occur in

congenital TTP therefore4 immunosuppression isnot indicated.Acute episo#es in congenital TTP treate# 2ith

P7G/plasma infusion alone in a similar 2ay to ac*uire# TTP$

Remission : treatment #epen#s on the phenotype ofthe in#ivi#ual pat$&ome patient 2/ congenital TTP re*uire plasma infusions every

8J 2eeDs in or#er to replace functional A%AMT&' an#prevent symptomatic TTP episo#es

Bthers 2ill only re*uire treatment in the conte3t of inciting

factors liDe pregnancy or infection$Pat 2/ congenital TTP have a signicant lifetime

e3posure to plasma use the safest pro#uctregar#ing viral/prion transmission$Bur stan#ar#: &%P


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&pecial CircumstancesPregnancy TTP may present #uring pregnancy TTP in pregnancy may represent ' of F processes:ac*uire# TTP #ue to the changes in immune regulation that

occur #uring pregnancyprecipitation of an episo#e of symptomatic TTP in a patient

2ith congenital TTP (2hich may or may not have beenpreviously recogni>e#"

Patient treate# 2/ methylpre#nisolone an# P7G in a

similar 2ay to pregnant patients$Rituximab is not advocated #uring pregnancy #ue

to unDno2n risDs to the fetus$%elivery of the baby does not necessarily result

in the resolution of the TTP episo#es$


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,+Iassociate# TTPimportant cause of secon#ary TTP$

Patients 2/ higher viral loa#s at presentation(9


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1uture #irections

)hile the outcomes of patients haveimprove# over time4 yet still signicantpotential for the #evelopment of newagents that target various aspects of the

#isease process4 inclu#ing:Recombinant A%AMT&'

AntiIv)1 nanobo#y

NIacetyl cysteine

Novel immunosuppressive agents


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Conclusions

Last #eca#e : signicant a#vances inun#erstan#ing pathological basis of TTP Result in improvement therapy that arerationally targete#$

&till4 thereQs room for improvement innumerous areas of patient care$


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ThanDyou

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Presentation Management of Thrombotic Thrombocytopenic Purpura