Thrombotic thrombocytopenic purpura

Thrombotic thrombocytic purpura (TTP) is a thrombotic microangiopathy characterised by thrombocytopaenia, microangiopathic haemolysis, neurological abnormalities, renal abnormalities, and low levels of a protein called ADAMTS-13.

It is primarily seen in adults and is typically caused by acquired autoantibodies against the enzyme cleaving von Willebrand factor, vWF, known as ADAMTS13. Deficiency of ADAMTS13 leads to excess vWF which in turn leads to microthrombus formation. These microthrombi also damage RBCs, causing haemolytic anaemia.

Rapid diagnosis and treatment are important to improve prognosis. It has high mortality untreated. It’s a rare disease, affecting 10 per million. Most cases are idiopathic, but some may be secondary to drugs, autoimmune disorders, etc.

Clinical features

The patients are typically previously healthy patients that acutely present with mental status changes, fever, petechiae and pallor. There is a pentad of symptoms to remember, but very few patients present with all five. Pentad of clinical findings:

1. Neurological symptoms (dizziness, seizures, coma)
2. Fever
3. Renal damage:
   1. Haematuria/proteinuria
   2. Oliguria or anuria
4. Symptoms of microangiopathic haemolytic anaemia:
   1. Jaundice
   2. Fatigue
   3. Dyspnoea
   4. Pallor
5. Symptoms of thrombocytopenia:
   1. Petechiae, purpuras
   2. Mucosal bleedings
   3. Prolonged bleeding after minor cuts

(Mnemonic for this: Nasty Fever Ruined My Tubes)

Diagnosis:

• Laboratory
  • Thrombocytopaenia
  • Haemolytic anaemia
  • Increased urea/BUN and creatinine
  • Normal leukocyte count
  • Elevated LDH
• Negative Coombs test
• Peripheral blood smear
  • Schistocytes – fragmented RBCs

Diagnosis can be confirmed by an ADAMTS13 activity assay, but it’s not necessary for the diagnosis. However, this test can take days, but treatment should begin immediately if there is clinical suspicion of TTP, as TTP can be a medical emergency.

Treatment

TTP requires urgent treatment, and therefore there is no time to delay treatment waiting for confirmation of for example ADAMTS13 deficiency.

The first-line treatment is plasma exchange, sometimes given together with corticosteroids. Plasma exchange is very efficacious.