TTP-HUS Thrombotic microangiopathy is marker for TTP/HUS as well as for DIC/DIC-like (secondary thrombotic microangiopathy-TMA), this giving us a first overlapping area. ADAMTS 13 (ADAMTS 13 Ab/ADAMTS 13 relative or absolute deficiency) - a recent marker for TTP, regulatory complement factors flaws (CFH, MCP-CD46, IF and CD46 Ab, CFH Ab as well)-pathogenetic elements in D- HUS, increased PAI 1-recently proved for TTP, all of this are nowadays valid pathogenetic lego bricks in that wall we call secondary TMA, this giving us our second overlapping area. Plasma exchange, grade IA recommendation for “true” TTP, has been gaining a place in the last decade in the supportive basket for secondary TMA(e.g., sepsis ), this giving us a third overlapping area. At least three overlapping areas and the lack of certain particular cases (malignant hypertension, HCT related TMA, D+ HUS early years) deliver us a syndrome (TMA) likely to be highly responsive to plasma exchange and, in certain situations, to tailored corticotherapy, monoclonal CD20 Ab, C5 Ab.

1. PREZENTARE DE CAZ
PURPURA TROMBOTICA
TROMBOCITOPENICA –SINDROMUL
HEMOLITIC UREMIC

2. 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.

3.  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 ͟ŵisĐarea͟ testelor de coagulare.
 Sindrom inflamator – neimpresionant.

4. Este transferata la SUUB pentru investigatii
suplimentare si tratament.
Admitem in STI o pacienta varstnica cu
disfunctie neurologica, renala si
͞heŵatologiĐa͟.
Este intubata si ventilata mecanic .

5. 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 hiperteŶsiv→ATN(si PTT-SHU)

6. 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.

9. Disfunctie
renala(context DZ
/HTA/hvol)
Disfunctie
neurologica
Interventie chir.
Si bacteriurie cu
E.Coli
MAHA si
Trombocitopenie

10. Anemie hemolitica
microangiopatica +
trombocitopenie + teste
coagulare ͞Ŷeŵiscate͟

12. TTP(thrombotic thrombocytopenic purpura)
Congenital TTP(Upshaw-Schulman
syndrome)
•Inherited ADAMTS 13 deficiency
Idiopathic TTP
•Aquired ADAMTS13 deficiency
•Without acquired ADAMTS13
deficiency
 Dupa Williams, 7th Ed

13. 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

14. 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

15. Secondary thrombotic microangiopathy 1
 Dupa Williams, 7th Ed

16. Secondary thrombotic microangiopathy 2
 Dupa Williams, 7th Ed

17. Secondary thrombotic microangiopathy 3
Bacterii

18. Secondary thrombotic microangiopathy 4
Medicamente

19. Secondary thrombotic microangiopathy 5
Diverse

20. 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

21. Patogeneza - TTP
Dupa Wintrobe,2009

22. Patogeneza - TTP

23. Patogeneza - TTP

24. Patogeneza – TTP
DefeĐte iŶ aĐtivitatea fiďriŶolitiĐa;tPA ↓ sau
PAI-1 ↑Ϳ
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

25. Patogeneza SHU D+

27. Care pe care?

28. • 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)

29. Patogeneza SHU D+
(Shiga toxin)
Proteoliza
Injurie endoteliala
Activare plachete
Fav. Rinichi prin asoc.Gb3

30. 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

31. 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

39. Pentade,triade si diade

40. Pentade,triade si diade
LDH
Schyzo
Trpenie

41. Pentade,triade si diade
Trpenie
HA
MA

43. TTP-HUS

45. Terapie

46. Terapie

47. Terapie - PLEX
TTP congenital
TTP idiopatic
HUS D – ?
HUS D + ?(adult)
• HUS D + copil
• Chimioterapie
• Posttransplant
• HUS D – ?
• HUS D + ?(adult)

48. Terapie - PLEX
• Zilnic 1 -2/zi
• 3-145 sedinte
• Oprire gradata
• LDH,Brb
0,08×G×(1-Ht)

49. Terapie
Corticoterapie(TTP
idiopatic, SHU D -)
Rituximab(Mabther
a)
Cyclosporine
Vincristine
Imunoglobuline
Infuzie PPC

50. Terapie - inutile
• Splenectomia
• Heparina
• Antiagregante plachetare

51. Succes

53. Bibliografie
Williams 2007
Wintrobe 2009
Uptodate 2011
Harrison 17th
Hillman
Emedicine
Oklahoma TTP-HUS registry