Thrombotic thrombocytopenic purpura

From IDWiki

Definition

  • Microangiopathic hemolytic anemia caused by autoantibodies to ADAMTS13 and characterized by anemia, thrombocytopenia, and, sometimes, renal failure, neuroloical symptoms, and fever

Pathophysiology

  • Autoantibodies to ADAMTS13, a metalloprotease that cleaves von WIllebrand factor (vWF)
  • Without ADAMTS13, vWF is not properly cleaved, causing microangiopathic thromboses that consume platelets and shear red cells

Differential Diagnosis

  • Atypical HUS
  • DIC
  • Other MAHAs

Epidemiology

  • 1 in 1m adults

Risk Factors

Clinical Manifestations

  • Suspect in any patient with evidence of [MAHA and thrombocytopenia]
  • Full pentad includes MAHA, thrombocytopenia, fever, neurological dysfunction, and renal dysfunction
  • If diarrhea or prominent renal failure, strongly consider HUS

Investigations

  • Diagnosis with ADATTS13 activity and inhibitor levels
  • Labs
    • CBC with blood film, retic count
    • Clotting times, which should be only mildly abnormal
    • LDH, haptoglobin, and fibrinogen, to diagnose MAHA and thrombocytopenia
    • U+E
    • Troponin
    • Liver panel
    • Amylase
    • TSH, calcium, DAT, blood group & screen
    • Pregnancy test, to rule out pregnancy-associated MAHA
    • ADAMTS13 level
    • Hepatitis A/B/C and HIV
    • Autoantibody screen

Management

  • If delay in starting plasma exchange, transfuse FFP and monitor for fluid overload
  • Primary treatment is plasma exchange
    • 1.5 plasma volumes x3 days, then 1 plasma volume daily
    • Stop 2 days after platelet normalization (over 150)
  • Alternative treatment if plasma exchange unavailable:
    • Plasma transfusions
  • Adjunct: methylprednisolone 1g/day or prednisone 1mg/kg/day with a PPI
    • Taper over weeks once platelets normalized
    • However, may be able to discontinue quickly after PLEX
  • Adjunct: folic acid 5mg po daily
  • If HIV: start HAART immediately
  • If neuro or cardiac involvement: start rituximab
  • If platelets > 50: start DVT prophylaxis and low-dose daily aspirin

Prognosis

  • Untreated, mortality is 90%, with half of deaths in the first 24 hours
  • Treated, mortality decreases to ~20%
    • 4% with PLEX, 25% without