TTPHUS

1
TTP/HUS

• Once thought of as separate clinical entities
  now more of a spectrum with HUS having more
  renal involvement, TTP more neurologic
• Multisystem disorders characterized by
  thrombocytopenia, microangiopathic hemolytic
  anemia (MAHA), organ ischemia, renal dysfunction,
  neurologic dysfunction.

2
Associations

• Most are idiopathic
• Some familial
• Infectious (E. coli O157H7, HIV)
• Autoimmune d/o (lupus)
• Pregnancy and postpartum
• Malignancy
• Chemotherapy (mitomycin, cisplatin, gemcitabine)
• Drugs (ticlodipine, clopidogrel, quinine, CSA)
• Post BMT

3
Pathogenesis

• Widespread formation of platelet microthrombi
  resulting in organ ischemia, consumptive
  thrombocytopenia
• Intravascular hemolysis due to fragmentation of
  RBCs as they transverse the partially occluded
  vessels
• Inciting event endothelial cell injury
• Some patients have been identified as having
  unusually large multimeric forms of vWF which is
  the result of an absent cleaving metalloprotease

4
Clinical Presentation

• TTP/HUS is uncommon but clinically important
  because of substantial morbidity and mortality
• These are also syndromes that need to be
  explained by an underlying cause (unless
  idiopathic)
• Incidence 3.7 cases per million but appears to be
  increasing
• Pentad MAHA, thrombocytopenia, fever,
  neurologic manifestations, renal dysfunction
• Ddx sepsis, DIC, systemic vasculitis,
  preeclampsia/eclampsia, malignant HTN,
  disseminated malignancy

5
Plasma exchange

• Theory behind it this gets rid of the unusually
  large vWF multimers and also gives back normal
  metalloproteinase or, removes the inhibitor to
  the metalloproteinase
• Before plasma exchange, mortality gt90
• After mortality lt20
• FFP infusion (if equipment unavailable) helpful
  but response rate 49 (78)

6
Ancillary therapy

• Steroids variably used no data
• Antiplatelet therapy no difference in outcomes
  of overall response or bleeding complications
• Platelet transfusions not unless major
  hemorrhage or invasive procedure
• Supportive care control of HTN, RBC
  transfusion, anticonvulsant therapy for seizures