title: Performance of a clinical prediction score for thrombotic thrombocytopenic purpura in an independent cohort.
abstract: OBJECTIVE
  Idiopathic thrombotic thrombocytopenic purpura (TTP) is a rare, clinically diagnosed disorder characterized by widespread intravascular platelet thrombosis. The pathophysiology involves acquired deficiency of ADAMTS13 (A disintegrin and metalloprotease with thrombospondin type 1 repeats), the enzyme responsible for cleavage of high molecular weight vonWillebrand factor multimers. Disease mortality is high, although prompt treatment with plasma exchange is generally effective. A readily available and highly reliable method of identifying ADAMTS13-deficient patients for appropriate plasma exchange is therefore of interest.
  
  
  METHODS
  Our initial study involved the assessment of multiple clinical and laboratory variables in patients with clinically suspected TTP for whom ADAMTS13 assay was performed. Five variables were found to be of significant predictive power. This enabled the development of a point-based scoring system to efficiently determine the likelihood of TTP and response to plasma exchange in a given patient. This current study involved a separate validation cohort of patients with clinically suspected TTP who underwent ADAMTS13 testing within two large healthcare systems in Utah between 2009 and 2011. The previously derived score was applied to this cohort and its performance was analysed. Additionally, the original and validation cohorts were combined to revisit the predictive power of individual variables and the five-variable prediction score.
  
  
  RESULTS
  A total of 84 (11 paediatric cases excluded) patients comprised the validation population. The percentage of TTP diagnoses in this group (10%) was identical to that in the initial cohort. Using an ADAMTS13 activity of <10% of normal, our original score correctly predicted or excluded severe ADAMTS13 deficiency in all patients in the second cohort when data for all variables was available. Individual variables retained predictive power and the performance of a three-variable parsimonious model, as well as the ultimate diagnoses for patients in the second cohort are described.
  
  
  CONCLUSIONS
  This work confirms the predictive power of a simple point-based score to exclude TTP as evidenced by severe ADAMTS13 deficiency in appropriately selected patients. It may enable clinicians to rapidly begin plasma exchange or to pursue an alternative cause of thrombotic microangiopathy.
authors.affiliation: Internal Medicine, University of Utah, Salt Lake City, UT, USA; Ogden Internal Medicine, Ogden, UT, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Bentley
authors.forename: A R
authors.initials: AR
authors.lastname: Wilson
authors.forename: G M
authors.initials: GM
authors.lastname: Rodgers
mesh_terms: D051722:ADAM Proteins / Q000172:deficiency*; D000071120:ADAMTS13 Protein; D015331:Cohort Studies; D006801:Humans; D010951:Plasma Exchange; D011697:Purpura, Thrombotic Thrombocytopenic / Q000175:diagnosis / Q000628:therapy*
chemical_list: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
keywords: ADAMTS13; haemolytic uraemic syndrome; plasma exchange; thrombotic microangiopathy; thrombotic thrombocytopenic purpura