TTP

• Thrombotic thrombocytopenia purpura is a type of microangiopathic haemolytic anaemia with a classic pentad of:

  • Fever
  • Thrombocytopenia
  • Haemolytic anaemia
  • Renal dysfunction
  • Neurological dysfunction
• TTP can either be congenital or acquired, acquired TTP is more common
• Acquired TTP:

  • Autoantibodies targeting ADAMTS13
• The less common congenital form of TTP results from mutations to ADAMTS13
• Individuals with hereditary ADAMTS13 deficiency remain asymptomatic until a triggering event such as an infection or pregnancy occurs
• Pathophysiology:

  • ADAMTS13 is a von Willebrand factor-cleaving protease
  • Low levels of ADAMTS13 result in microthrombi formation which leads to end organ ischaemia and damage
  • Spontaneous coagulation
• Symptoms:

  • Petechiae and purpura
  • Paleness or jaundice
  • Extreme tiredness
  • Fever
  • Tachycardia
  • SOB
  • Neurological - headache, speech changes, confusion, coma, stroke or seizure
  • Oliguria, proteinuria or haematuria
  • Nausea, vomiting, diarrhoea
• Risk factors for acquired TTP:

  • Antiplatelet drugs
  • Immunosuppressive drugs
  • HIV
  • Oestrogen
  • Pregnancy
  • Age - usually adults
  • Race - more common in African Americans
• Investigations:

  • ADAMTS13 assay
  • Bilirubin
  • Blood smear
  • FBC including platelets
  • Coombs test - will be negative (rules out other causes of haemolysis)
  • U&Es
  • LDH
  • Coagulation studies
• The diagnosis of TTP is suggested by

  • Thrombocytopenia and anemia
  • Fragmented red blood cells on the blood smear indicative of microangiopathic hemolysis (schistocytes: helmet cells, triangular RBCs, distorted-appearing RBCs)
  • Evidence of hemolysis (falling hemoglobin level, polychromasia, elevated reticulocyte count, elevated serum LDH and bilirubin, reduced haptoglobin)
  • Negative direct antiglobulin test
  • Normal coagulation profile
• Management:

  • Immune suppression: corticosteroids and rituximab
  • Acquired TTP - therapeutic plasma exchange (plasmaphersis) - removes antibodies against ADAMTS13
  • Inherited TTP - plasma infusion - replaces the missing or faulty ADAMTS13
• The PLASMIC score is calculated using findings on presentation and predicts the likelihood of ADAMTS13 activity being less than or equal to 10% to help make a presumptive diagnosis of TTP
• ADAMTS13 activity assays report the activity of the protease as a percentage of normal. An activity level of less than 10% confirms the diagnosis of TTP in patients with evidence of hemolysis and thrombocytopenia.
• Splenectomy is an option for in acquired treatment if other methods do not work as the spleen is where antibodies against ADAMTS13 are created
• Complications:

  • Fatal in 90% of patients without treatment
  • Stroke
  • Kidney failure
  • MI
  • Seizures
  • Haemorrhage