PREZENTARE DE CAZ

PURPURA TROMBOTICA

TROMBOCITOPENICA –SINDROMUL

HEMOLITIC UREMIC

Pacienta 74 ani, hipertensiva (tratata) si

diabetica, este internata la Spitalul Clinic

Caritas in vederea interventiei chirurgicale

pentru ruptura de perineu.

De retinut bacteriuria simptomatica

preoperator diagnosticata – germene

identificat E.Coli.

Evolutie imediat postoperator favorabila.

Ulterior, in cursul aceleiasi internari, la aproximativ 2-3 zile statusul neurologic al pacientei se altereaza – confuza, ulterior neresponsiva la stimuli verbali dar fara semne de focar.

Stabila hemodinamic si in respiratie spontana.

Penseaza diureza.

HLG – trombocitopenica, anemica (normocroma si normocitara), fara is area testelor de coagulare.

Sindrom inflamator – neimpresionant.

Este transferata la SUUB pentru investigatii

suplimentare si tratament.

Admitem in STI o pacienta varstnica cu

disfunctie neurologica, renala si

he atologi a .

Este intubata si ventilata mecanic .

Neurologic – nu raspunde la stimuli verbali si

nociceptivi, manifesta convulsii generalizate ce

cedeaza la benzodiazepine si examenul CT

cerebral nu releva modificari TD recente, in acord

cu examenul clinic neurologic ce nu a relevat

semne de focar.

Disfunctie renala – necesita terapie de epurare

extrarenala – CVVHDF.

La montarea CVC – PVC≈0 cm H2O(?)

Mecanism prerenal ≥12h asociat unui rinichi in

context diabetic si hiperte siv→ATN(si PTT-SHU)

HEMATOLOGIC...

Trombocitopenie.

Anemie normocroma normocitara.

LDH, bilirubina indirecta crescute.

Haptoglobina - lipsa kituri.

PT, APTT cvasinormale.

FDP prezenti (context postoperator!)

Fibrinogen normal spre crescut.

Frotiu sg. periferic – schizocite si coifuri (ER), policromatofilie, trombociti mari.Rar sferocite.

Test Coombs negativ.

Disfunctie renala(context DZ

/HTA/hvol)

Disfunctie neurologica

Interventie chir. Si bacteriurie cu

E.Coli

MAHA si Trombocitopenie

Anemie hemolitica

microangiopatica +

trombocitopenie + teste

coagulare e iscate

TTP(thrombotic thrombocytopenic purpura)

Dupa Williams, 7th Ed

Congenital TTP(Upshaw-Schulman

syndrome)

•Inherited ADAMTS 13 deficiency

Idiopathic TTP

•Aquired ADAMTS13 deficiency

•Without acquired ADAMTS13

deficiency

HUS(hemolytic uremic syndrome)

Diarrhea positive(infectious, Shiga

toxin associated)

• Sporadic

• Epidemic

Diarrhea negative

• Inherited complement regulatory

protein deficiencies(factor H,

membrane cofactor protein, factor I)

Dupa Williams, 7th Ed

Secondary thrombotic microangiopathy

CID de diverse cauze poate poza drept TTP-SHU in conditiile in care raportul consum factori coagulare-trombocite este mic.

Schizocitele, anemia hemolitica si trombocitopenia sunt multifactoriale si ...relative(vezi pac. Normal, valve protetice, HTA maligna)

1-18% pare a fi un interval larg si... cuprinzator

Unitate heterogena in patogeneza si raspuns la PLEX

Dupa Williams, 7th Ed

Secondary thrombotic microangiopathy 1

Dupa Williams, 7th Ed

Secondary thrombotic microangiopathy 2

Dupa Williams, 7th Ed

Secondary thrombotic microangiopathy 3

Bacterii

Secondary thrombotic microangiopathy 4

Medicamente

Secondary thrombotic microangiopathy 5

Diverse

Patogeneza

Usor de retinut cand e vorba de PTT

Si mai simplu la SHU D+

Un pic mai greu daca e SHU D-

Devastator la cele secundare

Patogeneza - TTP

Dupa Wintrobe,2009

Patogeneza - TTP

Patogeneza - TTP

Patogeneza – TTP

Defe te i a tivitatea fi ri oliti a tPA ↓ sau PAI-1 ↑

Nivel crescut de trombomodulina

Complexe imune altele decat ADAMTS13-IG

Anti CD36(ligand al ADAMTS13)

Injurie endoteliala(second hit)

Absenta HLA DR 53(protectiva)

Dupa Wintrobe,2009 Dupa Williams 7th

Patogeneza SHU D+

Care pe care?

• Tetrahymena (left) is approximately fifty times

the size of the bacteria it's trying to capture

but it's entirely vulnerable to the Shiga toxin

the bacteria carry in their DNA(E.Coli

O157:H7)

Patogeneza SHU D+

(Shiga toxin)

Proteoliza

Injurie endoteliala

Activare plachete

Fav. Rinichi prin asoc.Gb3

Patogeneza SHU D+

• Injurie vasculara colonica.

• Stim. direct agregarea plch.

• Stim. Expresia factorului tisular in celulele

tubului proximal.

• Senzitiveaza cel. epiteliale tubulare la

toxicitatea hemului.

• Expresie Gb3 diferita adult-copil.

• Creste expresia TNF renal

Patogeneza SHU D-

• Mutatii in cele 3 proteine reglatoare de

complement(CFH, MCP sau CD46, CFI sau IF)

• Autoanticorpi –anti MCP, anti CFH, anti IF

C5bC6C7C8C9-MAC

Pentade,triade si diade

Pentade,triade si diade

LDH

Trpenie

Schyzo

Pentade,triade si diade

Trpenie

HA

MA

TTP-HUS

Terapie

Terapie

Terapie - PLEX

TTP congenital

TTP idiopatic

HUS D – ?

HUS D + ?(adult)

• HUS D + copil

• Chimioterapie

• Posttransplant

• HUS D – ?

• HUS D + ?(adult)

Terapie - PLEX

• Zilnic 1 -2/zi

• 3-145 sedinte

• Oprire gradata

• LDH,Brb

0,08×G×(1-Ht)

Terapie

Corticoterapie(TTP

idiopatic, SHU D -)

Rituximab(Mabther

a)

Cyclosporine

Vincristine

Imunoglobuline

Infuzie PPC

Terapie - inutile

• Splenectomia

• Heparina

• Antiagregante plachetare

Succes

Bibliografie

Williams 2007

Wintrobe 2009

Uptodate 2011

Harrison 17th

Hillman

Emedicine

Oklahoma TTP-HUS registry