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?