thrombotic thrombocytopenic purpura (TTP)

Introduction

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

~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

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