managementul citopeniilor periferice in lupusul eritematos sistemic ppt
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Hepburn et al. The management of peripheral blood cyt0penias in SLE. Rheumatology 2010(Epub ahead of print).
Doi:10.1093/rheumatology/keq269
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IntroducereInteresarea hematologica
Frecventa in lupusInclusa in randul criteriilor de clasificare ACR
Anemie hemolitica cu reticulocitoza Leucopenie (<4.0 x 109/l) Limfopenie (<1.5 x /109/) x2 Trombocitopenie (<100 x 109/l)
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LeucopeniaManifestare tipica a LESEste rezultatul neutropenie/limfopeniei sau ambelorLeucocitoza per se – neobisnuita
Semn de infectie/ corticoterapie
Limfopenia 20-81% corelata cu activitatea bolii
Scadere LyT si LyB cu cresterea tipica a cel NKPatogenie necunoscuta
Anticorpi limfotoxici (30-90%) Reducerea expresiei unor proteine regulatoare de suprafata CD55, CD
59 pe leucocitele periferice expuse la liza mediata de complement Rolul IFN α/β – nivelul IFN α –invers corelat cu numarul Ly
Importanta determinarii necunoscuta
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LeucopeniaNeutropenia 47%
Patogeneza Mediata de Ac anti-neutrofilici Apoptoza neutrofilica excesiva mediata de TNF Compensata de celulele sistemului fagocitic (monocite),
care raman in circulatie Creste nivelul G-CSF caracteristic in LES
Daca se asociaza limfopeniei, neutropenia usoara fara rasunet clinic (rar – sepsis)
Neutropenia indusa medicamentos – nu se asociaza cu mortaliate crescuta
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LeucopeniaAlte cauze de leucopenie in lupus
Neutropenia Infectii Indusa medicamentos – frecvent: AZA, CF, MTX rar: MMF, CSA, HHQ Mielodisplazie Mielofibroza
Limfopenia Infectii (++virale) Indusa medicametos
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TrombocitopeniaTrombocitopenia 7-30% (58% - debut)
Patogeneza Mediata de Ac anti-trombocitari – cel mai adesea Mediata de Ac anti-fosfolipidici, anti-trombopoetina (TPO),
anti-receptor c-Mpl al TPO, anti CD40L
Acuta (+ severa) Debutul LES Asociata cu activitatea bolii – interesarea altor organe si
sisteme Raspunde la corticoterapie
Cronica Mai putin asociata cu activitatea bolii Raspuns mai slab la corticoterapie
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TrombocitopeniaAsociaza cu AH, alte citopenii, AAPLFactor de risc independent pentru mortalitate ridicata (alaturi de
GC doza mare)Asociata cu activitea bolii si hipocomplementemia
Alte cauze: Indusa medicamentos: frecvent - AZA, CF, MTX rar – HHQ, MMF, CSA, AINS, statine, IECA SAPL Infectii CID Uremie Mielodisplazie Trombocitopenie amegacariocitica Purpura trombotica trombocitopenica (PTT )– DD dificil Anemie hemolitica trombotica microangiopatica (Trpenie, AH micro-
angioptica, febra, sindroame neurologice, afectare renala)
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Abordarea citopeniilor (1)Anamneza medicamentoasa
Imunomodulatoare Lpenie+Trpenie: AZA, MTX Neutropenie: CF (nadir ziua 10)
Alte medicamente: statine, antibiotice, IECA
Sindrom de activare macrofagica Citopenia se instaleaza rapid LES juvenil
Semne/simptome de infectieSemne/simptome de limfoproliferare
Neutropenie+febra>38% hemoculturiPancitopenie sau suspiciune de aplazie pura linia rosie
parvo B19
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Abordarea citopeniilor (2)Investigatii
Frotiu sangvin – esentialAnemia asociata
Coombs, reticulocitii, analiza liniei rosiiAlte investigatii
LDH ASAT, ALAT Imunoglobuline Electroforeza proteinelor serice Studii hematologice – susp limfoproliferare
Anticorpii specifici (anti Tr/N/Ly) Utilitate controversata Rar indicati: trombocitopenia refractara
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Abordarea citopeniilor (3)Citologie medulara
Indicatii: leuco/trombocitopenie persistenta pancitopenie (++terapie mielotoxica AZA, MTX, CF)Evidentiaza
Aplazie (indusa med) Malignitati hematologice Hemofagocitoza
Cultura medulara: imunosupresati cu febra de etiologie necunoscuta
Aspecte comune in lupus Nr mare de precursori - distructie in periferie (mediata imun) Hipocelularitate mediata imun Necroza medulara Anomalii megacariocitare in trombocitopenii Numar mare de celule apoptotice
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Tratamentul citopeniilor (1)Leucopenia si trombocitopenie –
de regula usoare, nu necesita tratamentCorticoterapie – eficienta + prima intentie
TrombocitopeniaCorticoterapie
Daca: sindrom hemoragipar sau Tr<50x 109/l Tr penie severa Tr<20x 109/l 1mg/kg/zi Prednison (sau
pulse cu SM)Alternative la GC: AZA, CSASplenectomie
Trombocitopenia raspunde in general favorabil Dar – risc de flare, risc de boli autoimune asociate Profilaxie: antipneumococica, HI tip B, meningita C,
antigripala si penicilina V ++pacienti cu hipocomplementemie
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Tratamentul citopeniilor (2)IVIG
F eficienta si cu efect de durata trobocitopenie +manif neuropsihiatrice
Mecanism multimodal neutralizare Ac specifici, modularea prod de Ac si citokine, inhibitia
distrcutiei mediate de complement, modilarea functie LT+LB, apoptozei)SarcinaDoza terapeutica: 2g/kg – 5 doze consecutiv e de
400mg/kg
Citopenii refractareCiclofosfamida (10-15mg/kg sau 0.75-1g/m2)
Indicatii: citopenii severe+ anemie aplastica +PPT Adm IV – 4 luni sau scheme de adm la 2 saptamani Citologie medulara – anterior terapiei (raspuns bun daca
exista precursori multi)
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Tratamentul citopeniilor (3)Citopenii refractare
Plasmafereza Trombocitopenie aplazie linie rosie sindrom hemofagicitic AH trombotica micro-angiopatica
Terapii suportiveTransfuzii
Da preoperator <10x 109/l ! Trombocite – de evitat in trombocitopeniile mediate imun
Neutropenii febrile Antibiotice cu spectru larg (tazosin si gentamicina iv –
prima intentie) Prudenta la G-CSF (risc flare, efect tranzitor)
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Tratamentul citopeniilor (4)Terapii noi
Micofenolat mofetil tratamentul AH si trombocitopeniilor refractare Se poate asocia CSA in tratamentul aplazie de cel rosii ce
complica LES
Ciclofosfamida in doza imunoablativa (+/-transplatul de celule stem) Imunoablatia poate induce remisiune in boala severa si
refractara
Rituximab Eficient in: Trpenii, PTT, trombocitopenie amgegacariocitica Posibil eficiente si alte terapii de cel B (anti-BLyS –
Belimumab, etc)Antagonisti ai receptorilor de trombopoetinaIL11- factor de crestere trombocitara.
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…treating lupus..