thrombotic thrombocytopenic purpura (TTP)

see also:

• thrombocytopenia
• Idiopathic thrombocytopenic purpura (ITP)
• thrombosis with thrombocytopenia syndrome (TTS / VITT / VIPIT)
• haemolytic uraemic syndrome (HUS)
• disseminated intravascular coagulation (DIC)

• 1st described by Eli Moschcowitz in 1924
• it is a separate entity to haemolytic uraemic syndrome (HUS) which has a different pathophysiology due to shiga-toxin producing E.coli
• caused by autoantibodies to ADAMTS13 (a von Willebrand factor-cleaving protease) causing a deficiency which leads to accumulation of large multimers of von Willebrand factor which cause spontaneous platelet aggregation and thrombi

• 1 per 100,000 people
• 90% occur in adults

• ~half the cause is not known
• ~half have a known trigger:
  • sepsis
  • certain medications:
    • clopidogrel or ticlopidine
    • acyclovir
    • quinine
    • oxymorphone
    • quetiapine
    • etc
  • systemic lupus erythematosus (SLE)
  • pregnancy
  • HIV / AIDS
  • bone marrow transplantation
  • cancer
• rarely. genetic mutation:
  • Upshaw–Schulman syndrome - ADAMTS13 dysfunction is present from birth

• often have initial influenzal or diarrhoeal symptoms
• many have fever, tiredness, headaches and/or confusion
• some have sinus tachy or SOB and may have high BP
• thrombotic events which may cause a stroke
• thrombocytopenia which may cause a purpuric rash and bleeding such as from the gums
• also have microangiopathic hemolytic anemias (MAHAs)
• may also have neurologic abnormalities and renal impairment

• low platelet count
• coagulation profile is normal
• schistocytes
• elevated LDH
• indirect hyperbilirubinemia
• ADAMTS13 antibodies present
• ADAMTS13 < 10%

• haemolytic uraemic syndrome (HUS) has very similar clinical features although tends to have less neurologic abnormalities but higher rates of renal impairments
  • ADAMTS13 levels above 5%, coupled with a positive test for shiga-toxin/enterohemorrhagic E. coli (EHEC), are more likely indicative of HUS
• atypical haemolytic uraemic syndrome (HUS)
  • ADAMTS13 levels above 5%, coupled with a negative test for shiga-toxin/enterohemorrhagic E. coli (EHEC), are more likely indicative of atypical HUS

• emergent plasma exchange is the cornerstone of TTP treatment and reduces mortality from 90% to 20%
• in general, do not give platelets as makes it worse
• ?steroids
• ?rituximab