Ttp Hus Parikh
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Transcript of Ttp Hus Parikh
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Hemolytic-Uremic
SyndromePalak Parikh
Morning ReportAugust 1, 2007
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And TTP!
(Because they have many
of the same features)
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Incidence
Suspected TTP-HUS: 11 cases/million annually
Idiopathic TTP-HUS: 4.5 cases/million annually
Severe ADAMTS13 deficiency: 1.7cases/million annually- From the Oklahoma TTP-HUS Registry
* Incidence greater for women and for African Americans
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Classic Symptoms of
TTP-HUS
Microangiopathic hemolytic anemia (MAHA)
Thrombocytopenia
Acute renal insufficiency (more common in HUS)
Neurologic abnormalities (more common in TTP)
Fever
* Only thrombocytopenia and MAHA without another apparentetiology are required to initiate plasma exchange for presumed
TTP-HUS.
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TTP HUS
Reminder: Both are clinical diagnoses!
Adapted from Veyradier, A, et al. Blood 2001; 98:1765.
NUMBER OF SUBJECTS 66 45
Hemolytic Anemia 100 100
Thrombocytopenia 94 60
Neurologic changes 90 15
Acute Renal Failure 2 98
Fever 50 21
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Major Causes of TTP-HUS
Idiopathic: 37%
Drug-Associated: 13% Cyclosporine
Tacrolimus
Mitomycin C Bleomycin and cisplatin
Gemcitabine Quinine
Ticlopidine and clopidogrel
Autoimmune Disease: 13% Scleroderma
SLE APLA
Infection: 9% HIV Streptococcus pneumoniae
Pregnancy/Postpartum: 7%
Bloody Diarrhea Prodrome:6% Shiga toxin production (ex: E.
coli 0157:H7)
Shigella dysenteriae type 1
Verocytotoxin production by
Citrobacter freundii Hematopoietic cell
transplantation: 4%
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Differential Diagnosis
Vasculitis
Malignant Hypertension
DICAntiphosphospholipid Syndrome
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Labs to Look For
Schistocytes on peripheral smear
Elevated LDH
Decreased Haptoglobin Increased Creatinine
Thrombocytopenia (more pronounced in TTP
than HUS)
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ADAMTS13
(Another Lab to Order)
A Disintegrin-like And Metalloprotease with
ThromboSpondin type 1 repeats
Protease that cleaves ULVWf (Unusually Large
Von Willebrand factor) in the circulation
Decreased activity or inhibitor present in TTP,
but not HUS
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ADAMTS13
30 pts diagnosed with TTP: 6 pts. with familial TTP lacked all ADAMTS13
activity
24 pts. with nonfamilial TTP 20 had severe deficiency (
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Treatment
Plasma Exchange
Initially performed daily until platelet count
normalizes and hemolysis improved
Average of 7-16 daily exchanges needed
Prednisone (1 mg/kg/day PO) or
Methylprednisolone (125 mg IV BID)
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If Plasma Exhange Does not Work(occurs in 10-20% of patients)
Increase to twice daily Plasma Exchange
Rituximab +/- cyclophosphamide
Vincristine Intravenous immune globulin
Cyclosporine (* can cause TTP *)
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Possible Exceptions to
Plasma Exchange
HUS caused by bloody diarrhea prodrome
E. coli 0157:H7
Shigella
Strep Pneumoniae
Certain drugs
Mitomycin C
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Relapses
Relapses usually occur within the first year
Morbidity/mortality of relapses less than with
initial episodes
More relapses if pt. has severe ADAMTS13
deficiency or inhibitor at diagnosis
10-year relapse rate of 36%(Canadian Apheresis Trial)
* Indefinite Follow-up for Disease Recurrence
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Prognosis
Mortality up to 90% many years ago (without
plasma exchange)
Now, remission at 6 months approx. 80% with
plasma exchange
However, prognosis worse for pts. with disease
resistant to plasma exchange.
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Prognosis of HUS
With HUS caused by E. Coli O157:H7:
Mortality occurs in up to 3-5% of patients.
20% will develop CKD leading to ESRD.
With HUS associated with S. dysenteriae:
Mortality is greater, approaching 7%.
40% develop CKD.
With non-diarrhea associated HUS: Mortality up to 25% in acute illness.
Up to 50% will require continued RRT.
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Take Home Points
If TTP or atypical HUS is on top of your differential inpt. w/ MAHA and thrombocytopenia, institute plasmaexchange as soon as possible.
MAHA/thrombocytopenia are common to TTP andHUS. Neuro sxs are seen more often in TTP, whilerenal failure is seen in HUS.
ADAMTS13 deficiency or inhibitor is associated with
TTP. Classic/Typical HUS: Think E. coli 0157:H7 w/ shiga
toxin. There is no need for plasma exchange.
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References
Furlan, M, et al. Von Willebrand factor-cleaving protease inthrombotic thrombocytopenic purpura and the hemolytic-uremicsyndrome.NEJM1998; 339:1578.
Nangaku, M, et al. Pathogenesis and Prognosis of thrombotic
microangiopathy. Clin Exp Nephrol. 2007 Jun;11(2):107-14. Rose, Burton and George, James. TTP-HUS syndrome in
Adults. UptoDate. 2006.
Ruggenenti, P. Pathophysiology and management of thromboticmicroangiopathies.J Nephrol. 1998 Nov-Dec;11(6):300-10.
Veyradier, A, et al. Specific von Willebrand factor-cleavingprotease in thrombotic microangiopathies: a study of 111 cases.Blood2001; 98:1765.
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Questions?