thrombotic thrombocytopenic purpura

Question 1

definition

Answer 1

Thrombotic thrombocytopenic purpura (TTP) is a clinical syndrome characterised by microangiopathic haemolytic anaemia and thrombocytopenic purpura. Although the original descriptions included a pentad of microangiopathic haemolytic anaemia, thrombocytopenic purpura, neurological dysfunction, renal dysfunction, and fever, most patients do not have the entire pentad. There are no pathognomic features of TTP. Without treatment, TTP is typically fatal. Pathophysiology can involve the absence of von Willebrand factor cleaving enzyme (ADAMTS-13), resulting in unusually large von Willebrand multimers that lead to platelet aggregation and subsequent thrombocytopenia and microthrombi. Some evidence suggests that at least 33% of patients with idiopathic TTP may have severe ADAMTS-13 deficiency.

TTP is one of the considerations when deciphering the broader clinical presentation of thrombotic microangiopathy, which may be clinically similar but distinct in etiopathogenesis and treatment. Haemolytic uraemic syndrome is a similar syndrome but usually has a more pronounced renal component and is caused by Shiga toxin produced by certain E coli infections. Atypical haemolytic uraemic syndrome (aHUS) is a complement-mediated microangiopathy which clinically may masquerade as TTP, but is due to abnormalities in complement regulation.

HUS and TTP can occur together

Question 2

symptoms

Answer 2

severe neurological symptoms:
- coma, focal abnormalities, seizure
mild neurological symptoms:
- headache, confusion

• fever
• bleeding symptoms (purpura, ecchymosis, menorrhagia)

Question 3

risk factors

Answer 3

• black ethnicity, female
• obesity
• pregnancy
• cancer therapies
• use of quinine (anti malarial), clopidogrel (and other antiplatelets)

Question 4

investigations

Answer 4

• platelet count => low
• reticulocyte count => raised
• haemoglobin => low
• haptoglobin => low
• peripheral blood smear
• urinalysis, urea and creatinine (check kidney involvment)
• direct coombs’ test ( to rule out autoimmune haemolytic anaemia) => negative
• can do ADAMTS13 activity assay, but may not necessarily be useful for treatment