Thrombotic thrombocytopenic purpura

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

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