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
