Thrombotic thrombocytopenic purpura (TTP)

Key facts

• Overlap with HUS and often considered a spectrum with HUS
• Symptoms and signs of TTP usually more severe than HUS
• Unexplained thrombocytopenia + anaemia → prompt investigation
• Diagnosis made clinically

Pathophysiology

• Genetic or acquired deficiency of a protease (ADAMTS13) which normally cleaves multimers of vWF → large vWF forms → causes platelet aggregation and fibrin deposition in small vessels

Aetiologies

• Idiopathic (40%)
• Autoimmune (SLE)
• Cancer
• Pregnancy (rule out HELLP syndrome first)
• Drug associated (e.g. quinine)
• Bloody diarrhoea prodrome (as childhood HUS)
• Haemopoietic stem cell transplantation

Diagnosis

• Clinical diagnosis by 5 clinical features
  1. Microangiopathic Haemolytic Anaemia (MAHA)
  2. thrombocytopenia
  3. AKI (less marked than HUS)
  4. CNS symptoms (headache, palsies, seizure, coma) (more marked than HUS)
  5. Fever

Investigations

• RBC↓ and platelets↓
• ↑Reticulocyte count
• ↑LDH and ↑Bil
• Direct Coombs’ test -ve (thus r/o autoimmune haemolytic anaemia)
• ↑Urea and ↑creatinine
• Peripheral blood smear- schistocytes

Management

• Plasma exchange (time critical; within 24 hours)
• Prednisolone
• Other options: Caplacizumab, Aspirin, folic acid and/or transfusion, immunosuppression, splenectomy
• Long term aspirin after recovery