title: Von Willebrand factor-cleaving protease (ADAMTS-13) activity in thrombotic microangiopathies: diagnostic experience 2001/2002 of a single research laboratory.
abstract: BACKGROUND
  Severe deficiency of von Willebrand factor-cleaving protease (ADAMTS-13) activity (<5% of normal) is specific for classical thrombotic thrombocytopenic purpura (TTP), a disorder presenting with thrombocytopenia, microangiopathic haemolytic anaemia and often with organ dysfunction such as neurological symptoms, renal failure, and fever. A certain, though according to several case series, variable percentage of patients with clinically diagnosed TTP and most patients with other forms of thrombotic icroangiopathies (TMA) do not show severe ADAMTS-13 deficiency.
  
  
  METHODS
  We determined ADAMTS-13 activity in 508 plasma samples of 309 patients referred to our laboratory in 2001 and 2002. Plasma samples with ADAMTS-13 activity <5% were additionally tested for the presence of inhibitory antibodies. Patients were assigned to ten predefined clinical categories according to information provided in the referral letter (TMA not specified; TMA associated with neoplasia or chemotherapy; TMA following haematopoietic stem cell transplantation; TMA with additional disorder; idiopathic TTP; haemolytic-uraemic syndrome (HUS) not specified; HUS with diarrhoea prodrome; atypical HUS; other haematological disorder; no clinical information available).
  
  
  RESULTS
  We detected 50 (16%) patients with severe ADAMTS-13 deficiency. Forty-four (88%) of these patients had been classified as idiopathic TTP, 2 as neoplasia- or chemotherapy-associated, and 4 as non-specified TMA. Among the patients labelled as acute idiopathic TTP, the prevalence of severe ADAMTS-13 deficiency was 63% (44/70). Inhibitory antibodies were found in 31 (62%) patients with ADAMTS-13 activity <5%. Of the 44 patients with acute idiopathic TTP, at initial presentation or at relapse, with ADAMTS-13 activity <5%, 11 were identified to have (probable) constitutional severe ADAMTS-13 deficiency.
  
  
  CONCLUSIONS
  Severe ADAMTS-13 deficiency is found in about 60% of patients diagnosed with idiopathic TTP but in none of 111 diagnosed with HUS. Plasma ADAMTS-13 activity <5%, however, does not identify all patients clinically diagnosed with TTP. Detection of inhibitory antibodies against ADAMTS-13 helps to differentiate between acquired and constitutional forms of TTP, which may be important for treatment strategies.
authors.affiliation: Central Haematology Laboratory, Inselspital, University of Bern, Bern, Switzerland.
authors.forename: J-D
authors.initials: JD
authors.lastname: Studt
authors.forename: J A
authors.initials: JA
authors.lastname: Kremer Hovinga
authors.forename: L
authors.initials: L
authors.lastname: Alberio
authors.forename: V
authors.initials: V
authors.lastname: Bianchi
authors.forename: B
authors.initials: B
authors.lastname: Lämmle
mesh_terms: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D005260:Female; D006801:Humans; D007753:Laboratories; D008297:Male; D008666:Metalloendopeptidases / Q000097:blood*; D008875:Middle Aged; D011697:Purpura, Thrombotic Thrombocytopenic / Q000175:diagnosis / Q000201:enzymology*
chemical_list: D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human