Peripheral smear

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Peripheral smear
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HUS-TTP

• A spectrum of disease HUS with more renal
  involvement and TTP with more CNS involvement
• Laboratory features MAHA, thrombocytopenia,
  renal dysfunction coagulation usually preserved
• Endothelial cell injury is the inciting event
• Triggers can include bacterial toxins, antibodies
  or immune complex, drugs, abnormal vWF

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Childhood HUS

• HUS in children initiated by infection is
  separated from other forms because outcome and
  response to therapy differ
• Treatment is mainly supportive
• Not a benign disease 50 requrie dialysis, 75
  require PRBCs, 25 will have neurologic
  dysfunction (seizures, coma), long term renal dys
  in 39

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Childhood HUS

• Other variants
• Neuramidase-associated Strep pneumonia
  infections (pneumonia, meningitis), very severe
• Aytpical or familial HUS familial, tends to
  recur, can follow infections (30, usu. URI) but
  may be sporadic, resembles TTP in that neurologic
  sxs predominate and

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HUS/TTP in adults

• The term HUS was introduced in 1954
• Syndrome was described 1924 after an outbreak of
  Shigella dysenteriae followed by purpura, anuria,
  and neurologic symptoms
• E. coli O157H7 outbreaks with HUS occurred later
• LPS and/or Shiga or Shiga-like toxins are
  implicated

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HUS/TTP in adults

• Other variants
• Acute idiopathic
• Chronic relapsing
• Drug associated (CSA, clopidogrel, etc)
• Other infections (viral, HIV)
• Post BMT

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Inherited forms

• Over the past 20 years, 140 cases of familial
  HUS/TTP described in 70 families
• Both autosomal dominant and autosomal recessive
  modes have been recognized
• Some of these (minority) followed infections
  (HUS), most were recurrent which responded to
  plasmapheresis (TTP)
• Inherited abnormalities of complement
  abnormally low levels of C3 (with normal C4)
  reflects possible normalities in the classic
  pathway activation

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Inherited forms

• Lack of or altered function of factor H
• Factor H prevents the formation of C3bBb
  complexes and accelerates the dissociation of the
  complex from C3 convertase thereby limiting
  complement activation
• Very low factor H levels have been demonstrated
  in large series of families with a history of
  HUS/TTP
• A gene mutation has been mapped to an area on
  chromosome 1q which segregates with HUS

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Treatment options

• Childhood HUS supportive
• Everything else trial of plasma exchange
• Can change to plasma cryosupernatant, prednisone,
  or vincristine if not responding
• Follow platelet count and LDH
• Drug induced discontinue offending agent