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
