Thrombotic Thrombocytopenic Purpura (TTP)

Presentation :

• Often presents with GI and neurological symptoms
• Typically presents WITHOUT renal failure (unlike other MAHAs like Atypical HUS (Compliment Mediated HUS) which often have florid renal failure)

Pathophysiology :

• Deficiency of ADAMSTS13:
  • Congenital: occurs typically early in life (pediatric) so less likely to be seen by IM
  • Acquired: Autoantibodies inhibit ADAMSTS13 activity
• ADAMSTS13 works to cleave vWF multimers into shorter chains. When vWF gets really long they more readily bind platelets and cause thrombosis
  • 

Diagnostic Testing:

• CBC w/ smear, Coags, Fibrinogen, LDH, Haptoglobin, ADAMSTS13 level
• PLASMIC score to help predict ADAMSTS13 deficiency
  • 
• ADAMSTS13 activity

Treatment :

• 1st Line Therapies:
  • Plasma exchange
    • Removes long-chain vWF
    • Replaces ADAMSTS13
    • Removes ADAMSTS13 auto-antibodies
  • Corticosteroids
    • Suppresses plasma cells producing anti-ADMAMSTS13 autoantibodies
  • Rituximab
    • Eliminates plasma cells producing anti-ADMAMSTS13 autoantibodies
    • Doesn't reduce mortality but reduces # of plasma exchanges needed, duration of treatment/hospitalization, and prevents relapse
• Bortezomib
  • Can consider in treatment failure
• Caplacizumab
  • Binds the A1 domain of vWF which normally binds platelets, preventing platelet aggregation
  • New agent, not on all formularies
  • Not clear exactly where this fits into treatment algorithms
• Transfusion
  • Clinically significant bleeding is rare despite severe thrombocytopenia. Avoid platelet transfusions unless significant bleeding occurs, or an high bleed-risk procedure is required.

Prognosis:

• Very high mortality in the first 24 hours

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